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Ho FC, Chung HW, Yu CH, Huang CY, Liang FW. Timing of antenatal corticosteroid exposure and its association with childhood mental disorders in early- and full-term births: A population-based cohort study. Eur J Pediatr 2025; 184:181. [PMID: 39912937 DOI: 10.1007/s00431-025-05994-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 01/11/2025] [Accepted: 01/16/2025] [Indexed: 02/07/2025]
Abstract
Although the administration of antenatal corticosteroids (ACS) is generally recognized as cost-effective and beneficial, recent studies have indicated potential long-term adverse effects on neurodevelopment, particularly for term-born infants. However, limited research has explored the association between the timing of ACS exposure, gestational age (GA) at birth, and their potential implications for mental and behavioral outcomes in offspring compared to non-exposed infants. This study aimed to examine the association between the timing of antenatal corticosteroid (ACS) exposure for threatened preterm labor and childhood mental disorders among early-term and full-term births. All eligible term infants born between 2010 to 2014 were included in this nationwide study and followed until the end of 2021. The primary outcome was any childhood mentaldisorders, with secondary outcomes being attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental delay (DD). Compared to unexposed infants, ACS exposure before 34 weeks of GA increased the risk of developing mental behavior disorders. Exposure to ACS before 34 weeks was significantly associated with an increased risk of ADHD and DD; however, this association was observed only in early-term births but not in those born at full-term. CONCLUSION Our finding suggests a need for further investigation into the influence of GA at birth on these disorders and supports that the risk of childhood mental disorders in term infants varied among different ACS exposure timing. WHAT IS KNOWN • While administration of antenatal corticosteroids (ACS) for preterm birth threats is widely acknowledged as both cost-effective and beneficial, recent studies have raised concerns about potential long-term adverse effects on neurodevelopment, particularly in term-born infants. • Previous studies have found that early-term birth is associated with lower intelligence, ADHD, and poorer school performance compared to full-term birth. WHAT IS NEW • There is an interaction between the timing of ACS treatment and gestational age at birth with respect to the likelihood of neurodevelopmental outcomes in term-born infants. • Exposure to ACS before 34 weeks is associated with an increased risk of any childhood mental disorders, specifically ADHD and DD, among early-term births, whereas this association was not observed in infants who reached full-term gestation.
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Affiliation(s)
- Fong-Cheng Ho
- Division of Neonatology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
- Department of Pediatrics, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, 820, Taiwan
| | - Hao-Wei Chung
- Division of Neonatology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
- Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
- Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan
- Department of Pediatrics, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, 812, Taiwan
| | - Chia-Hung Yu
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, 710, Taiwan
- Department of Computer Science and Information Engineering, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan
| | - Chiao-Yun Huang
- Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Fu-Wen Liang
- Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
- Center for Big Data Research, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
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St Clair SL, Walters AGB, Crowther CA, Dalziel SR, Eagleton C, Gamble GD, McKinlay CJD, Milne BJ, Harding JE, for the ANCHOR Study Group. Reproductive outcomes after antenatal corticosteroids: Secondary analysis of 50-year follow-up of the Auckland steroid randomized trial. Acta Obstet Gynecol Scand 2024; 103:2412-2425. [PMID: 39365094 PMCID: PMC11610002 DOI: 10.1111/aogs.14984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 09/10/2024] [Accepted: 09/19/2024] [Indexed: 10/05/2024]
Abstract
INTRODUCTION Antenatal corticosteroids are widely used to prevent morbidity and mortality after preterm birth, but there are ongoing concerns about the possible risk of long-term adverse effects, including perturbation of endocrine systems, with potential implications for reproduction. A small number of animal studies have suggested possible adverse effects on reproduction after antenatal exposure to corticosteroids, but there is a paucity of human data. MATERIAL AND METHODS This is a secondary cohort analysis of the 50-year follow-up of the Auckland Steroid Trial (1969-1974) comparing antenatal exposure to corticosteroids or placebo. Participants whose mothers took part in the placebo-controlled randomized trial of antenatal corticosteroids completed a questionnaire reporting reproductive outcomes at 50 years of age. The main outcome was at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks. Additional outcomes included a number of pregnancies or fathered pregnancies ≥20 weeks, outcomes relating to female reproductive lifespan (including age at menarche and menopause), and outcomes relating to their offspring (including birthweight and gestation). RESULTS Of 917 eligible participants, 415 (45% of eligible) completed the questionnaire at a mean (SD) age of 49.3 (1.0) years. The proportion of participants who had experienced at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks was similar in betamethasone and placebo-exposed groups (163/217 [75%] vs. 136/190 [72%]; RR 1.08, (95% CI 0.95 to 1.22); p = 0.23). Participants exposed to betamethasone had a slightly higher number of pregnancies or fathered pregnancies ≥20 weeks compared to those exposed to placebo (mean 1.89 vs. 1.60; marginal mean difference 0.20, (95% CI 0.03-0.37); p = 0.03). Other outcomes, including female reproductive lifespan and offspring-related outcomes, were similar in both randomized groups. There were also no differences in any outcomes between those born preterm and those born at term. CONCLUSIONS Antenatal exposure to corticosteroids appears to have no clinically important effect on reproductive outcomes to 50 years.
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Affiliation(s)
| | | | | | - Stuart R. Dalziel
- Department of Pediatrics: Child and Youth HealthUniversity of AucklandAucklandNew Zealand
- Department of Surgery: Child and Youth HeathUniversity of AucklandAucklandNew Zealand
- Children's Emergency DepartmentStarship Children's HospitalAucklandNew Zealand
| | - Carl Eagleton
- Liggins InstituteThe University of AucklandAucklandNew Zealand
| | | | | | - Barry J. Milne
- School of Social Sciences and Centre of Methods and Policy Application in the Social SciencesUniversity of AucklandAucklandNew Zealand
- Department of Statistics, Faculty of ScienceUniversity of AucklandAucklandNew Zealand
| | - Jane E. Harding
- Liggins InstituteThe University of AucklandAucklandNew Zealand
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McPherson CB, O’Donnell L, Moes E, Edgar H. No relationship found between dental fluctuating asymmetry, birthweight, and birth term in two modern North American samples. Am J Hum Biol 2024; 36:e24114. [PMID: 38842218 PMCID: PMC11623129 DOI: 10.1002/ajhb.24114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 04/24/2024] [Accepted: 05/28/2024] [Indexed: 06/07/2024] Open
Abstract
OBJECTIVE Deciduous dental crowns primarily develop during gestation and early infancy and embody early life stress exposures. Composite measures of dental fluctuating asymmetry (DFA) generated from the deciduous teeth may therefore indicate cumulative gestational stress in developmental origins of health and disease (DOHaD) studies. This study examines whether higher composite measures of deciduous DFA are associated with low birthweight and prematurity, two aspects of birth phenotype consistently associated with increased morbidity and mortality risks in adulthood. SUBJECTS AND METHODS We evaluated associations between composite deciduous DFA, birthweight, and birth term in two contemporary North American samples: an autopsy sample from New Mexico (n = 94), and sample from a growth cohort study in Burlington, Ontario (n = 304). Dental metric data for each sample was collected from postmortem CT scans and dental casts, respectively. Composite DFA was estimated using buccolingual (BL) and mesiodistal (MD) crown diameters from paired deciduous teeth. RESULTS Contrary to expectations, the results of linear regression indicated no significant relationship between birthweight and DFA, or birth term and DFA, in either sample. CONCLUSIONS Deciduous DFA does not predict aspects of birth phenotype associated with gestational stress. Birthweight and birth term are plastic relative to the more developmentally stable deciduous dentition, which may only subtly embody early life stress. We suggest that deciduous DFA should be utilized with caution in DOHaD studies until its relationship with gestational stress is clarified.
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Affiliation(s)
- Cait B. McPherson
- Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Lexi O’Donnell
- College of Population Health, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
- Department of Anthropology, University of New Mexico, Albuquerque, NM, USA
| | - Emily Moes
- Department of Anthropology, University of New Mexico, Albuquerque, NM, USA
- Department of Physician Assistant Studies, University of St. Francis, Albuquerque, NM
| | - Heather Edgar
- Department of Anthropology, University of New Mexico, Albuquerque, NM, USA
- Office of the Medical Investigator, University of New Mexico, Albuquerque, NM
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Ngema M, Xulu ND, Ngubane PS, Khathi A. Pregestational Prediabetes Induces Maternal Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation and Results in Adverse Foetal Outcomes. Int J Mol Sci 2024; 25:5431. [PMID: 38791468 PMCID: PMC11122116 DOI: 10.3390/ijms25105431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 04/24/2024] [Accepted: 04/29/2024] [Indexed: 05/26/2024] Open
Abstract
Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, leading to adverse foetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on foetal HPA axis function and postnatal offspring development. Hence, this study investigated the effects of pregestational prediabetes on maternal HPA axis function and postnatal offspring development. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone, were measured in all dams and pups. Glucose tolerance, insulin and gene expressions of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase basal ACTH and corticosterone concentrations, disturbed MR and GR gene expression, glucose intolerance and insulin resistance assessed via the Homeostasis Model Assessment (HOMA) indices in the pups born from the PD group compared to NPD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.
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Affiliation(s)
| | | | | | - Andile Khathi
- School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Westville, Private Bag X54001, Durban 4041, KwaZulu Natal, South Africa; (M.N.); (N.D.X.); (P.S.N.)
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Akbarinejad V, Cushman RA. Developmental programming of reproduction in the female animal. Anim Reprod Sci 2024; 263:107456. [PMID: 38503204 DOI: 10.1016/j.anireprosci.2024.107456] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 03/09/2024] [Accepted: 03/12/2024] [Indexed: 03/21/2024]
Abstract
Successful reproduction is a cornerstone in food animal industry in order to sustain food production for human. Therefore, various methods focusing on genetics and postnatal environment have been identified and applied to improve fertility in livestock. Yet there is evidence indicating that environmental factors during prenatal and/or neonatal life can also impact the function of reproductive system and fertility in the animals during adulthood, which is called the developmental programming of reproduction. The current review summarizes data associated with the developmental origins of reproduction in the female animals. In this regard, this review focuses on the effect of plane of nutrition, maternal body condition, hypoxia, litter size, maternal age, parity, level of milk production and milk components, lactocrine signaling, stress, thermal stress, exposure to androgens, endocrine disrupting chemicals, mycotoxins and pollutants, affliction with infection and inflammation, and maternal gut microbiota during prenatal and neonatal periods on the neuroendocrine system, puberty, health of reproductive organs and fertility in the female offspring. It is noteworthy that these prenatal and neonatal factors do not always exert their effects on the reproductive performance of the female by compromising the development of organs directly related to reproductive function such as hypothalamus, pituitary, ovary, oviduct and uterus. Since they can impair the development of non-reproductive organs and systems modulating reproductive function as well (e.g., metabolic system and level of milk yield in dairy animals). Furthermore, when these factors affect the epigenetics of the offspring, their adverse effects will not be limited to one generation and can transfer transgenerationally. Hence, pinpointing the factors influencing developmental programming of reproduction and considering them in management of livestock operations could be a potential strategy to help improve fertility in food animals.
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Affiliation(s)
- Vahid Akbarinejad
- Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
| | - Robert A Cushman
- USDA, Agricultural Research Service, US. Meat Animal Research Center, Clay Center, NE 68933-0166, United States
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Karahoda R, Vachalova V, Portillo R, Mahrla F, Viñas-Noguera M, Abad C, Staud F. Developmental expression of catecholamine system in the human placenta and rat fetoplacental unit. Sci Rep 2024; 14:6948. [PMID: 38521816 PMCID: PMC10960862 DOI: 10.1038/s41598-024-57481-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 03/18/2024] [Indexed: 03/25/2024] Open
Abstract
Catecholamines norepinephrine and dopamine have been implicated in numerous physiological processes within the central nervous system. Emerging evidence has highlighted the importance of tightly regulated monoamine levels for placental functions and fetal development. However, the complexities of synthesis, release, and regulation of catecholamines in the fetoplacental unit have not been fully unraveled. In this study, we investigated the expression of enzymes and transporters involved in synthesis, degradation, and transport of norepinephrine and dopamine in the human placenta and rat fetoplacental unit. Quantitative PCR and Western blot analyses were performed in early-to-late gestation in humans (first trimester vs. term placenta) and mid-to-late gestation in rats (placenta and fetal brain, intestines, liver, lungs, and heart). In addition, we analyzed the gene expression patterns in isolated primary trophoblast cells from the human placenta and placenta-derived cell lines (HRP-1, BeWo, JEG-3). In both human and rat placentas, the study identifies the presence of only PNMT, COMT, and NET at the mRNA and protein levels, with the expression of PNMT and NET showing gestational age dependency. On the other hand, rat fetal tissues consistently express the catecholamine pathway genes, revealing distinct developmental expression patterns. Lastly, we report significant transcriptional profile variations in different placental cell models, emphasizing the importance of careful model selection for catecholamine metabolism/transport studies. Collectively, integrating findings from humans and rats enhances our understanding of the dynamic regulatory mechanisms that underlie catecholamine dynamics during pregnancy. We identified similar patterns in both species across gestation, suggesting conserved molecular mechanisms and potentially shedding light on shared biological processes influencing placental development.
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Affiliation(s)
- Rona Karahoda
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Prague, Czech Republic
| | - Veronika Vachalova
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Prague, Czech Republic
| | - Ramon Portillo
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Prague, Czech Republic
| | - Filip Mahrla
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Prague, Czech Republic
| | - Mireia Viñas-Noguera
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Prague, Czech Republic
| | - Cilia Abad
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Prague, Czech Republic
| | - Frantisek Staud
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Prague, Czech Republic.
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Bagheri F, Goudarzi I, Lashkarbolouki T, Elahdadi Salmani M, Goudarzi A, Morley-Fletcher S. Improving behavioral deficits induced by perinatal ethanol and stress exposure in adolescent male rat progeny via maternal melatonin treatment. Psychopharmacology (Berl) 2024; 241:153-169. [PMID: 37889278 DOI: 10.1007/s00213-023-06470-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 09/25/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND AND AIM Early-life stressful situations and binge drinking have been thus far acknowledged as two burdensome conditions that potentially give rise to negative outcomes and then synergistically affect brain development. In this context, the hippocampus, with the greatest number of glucocorticoid receptors (GCRs) in the brain, is responsible for regulating negative responses to stress. Prolonged glucocorticoid (GC) exposure can accordingly cause oxidative stress (OS), leading to cognitive and emotional dysfunction. Against this background, melatonin, as a powerful antioxidant and hypothalamus-pituitary-adrenal (HPA) axis regulator, was administered in this study to ameliorate cognitive impairments induced by perinatal ethanol and stress exposure in adolescent male rat progeny. METHODS Wistar rat dams were exposed to ethanol (4 g/kg) and melatonin (10 mg/kg) from gestational day (GD) 6 to postnatal day (PND) 14 and then limited nesting material (LNS) from PND0 to PND14 individually or in combination. Maternal behavior was then investigated in mothers. Afterward, the plasma corticosterone (CORT) concentration, the OS marker, the corticotropin-releasing hormone receptor type 1 (CRHR1) expression, and the GCR and brain-derived neurotrophic factor (BDNF) levels were measured in the male pups. Moreover, behavioral tasks, including the elevated plus maze (EPM), the Morris water maze (MWM), the novel object recognition (NORT), and the object-location memory (OLM) tests were completed and assessed. RESULTS The quantity and quality of maternal care significantly decreased in the mothers with dual exposure to ethanol and stress. The plasma CORT concentration in the progeny also dropped in the Ethanol + LNS group, but the risk-taking behavior elevated significantly. The ethanol and stress exposure further revealed a significant fall in the GCR and CRHR1 expression levels, compared with stress alone. The results of learning and memory tasks also indicated a significant reduction in spatial learning and memory among animals exposed to ethanol and stress. The BDNF mRNA levels correspondingly increased in the Ethanol + LNS group, compared with LNS alone. In the presence of ethanol and stress, the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities correspondingly declined. On the other hand, the malondialdehyde (MDA) levels augmented in the hippocampus of the animals with ethanol and LNS dual exposure, as compared with the control group. Melatonin treatment (MT) thus improved nursing behaviors in dams, prevented OS, enhanced the CRHR1 and GCR expression, and reduced the BDNF levels to the similar ones in the control group. The animals in the Ethanol + LNS + MT group ultimately showed an ameliorated performance at behavioral tasks, including the memory and risk-taking behavior. CONCLUSION It was concluded that MT could prevent stress response and memory impairments arising from dual exposure to ethanol and stress by inhibiting OS.
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Affiliation(s)
| | - Iran Goudarzi
- School of Biology, Damghan University, Damghan, Iran.
| | | | | | - Afsaneh Goudarzi
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Morley-Fletcher
- Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale Et Fonctionnelle, 59000, Lille, France
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Khoury JE, Atkinson L, Jack S, Bennett T, Raha S, Duku E, Gonzalez A. Protocol for the COVID-19 Wellbeing and Stress Study: a longitudinal study of parent distress, biological stress and child biopsychosocial development during the pandemic and beyond. BMJ Open 2023; 13:e071926. [PMID: 37580092 PMCID: PMC10432660 DOI: 10.1136/bmjopen-2023-071926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 05/22/2023] [Indexed: 08/16/2023] Open
Abstract
INTRODUCTION The COVID-19 pandemic has had a unique impact on the mental health and well-being of pregnant individuals and parents of young children. However, the impact of COVID-19-related stress during pregnancy on early child biopsychosocial development, remains unclear. The COVID-19 Wellbeing and Stress Study will: (1) investigate the impact of different forms of prenatal stress experienced during the pandemic (including objective hardship, perceived psychological distress and biological stress) on child stress biology, (2) examine the association between child stress biology and child developmental outcomes, (3) determine whether child stress biology acts as a mechanism linking prenatal stress to adverse child developmental outcomes and (4) assess whether gestational age at the onset of the COVID-19 pandemic or child sex, moderate these associations. METHODS AND ANALYSES The COVID-19 Wellbeing and Stress Study is a prospective longitudinal study, consisting of six time points, spanning from pregnancy to 3 years postpartum. The study began in June 2020, consisting of 304 pregnant people from Ontario, Canada. This multimethod study is composed of questionnaires, biological samples, behavioural observations and developmental assessments ETHICS AND DISSEMINATION: This study was approved by the Hamilton Integrated Research Ethics Board (#11034) and the Mount Saint Vincent University Research Ethics Board (#2020-187, #2021-075, #2022-008). Findings will be disseminated through peer-reviewed presentations and publications, community presentations, and electronic forums (social media, newsletters and website postings).
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Affiliation(s)
- Jennifer E Khoury
- Department of Psychology, Mount Saint Vincent University, Halifax, Nova Scotia, Canada
| | - Leslie Atkinson
- Department of Psychology, Toronto Metropolitan University, Toronto, Ontario, Canada
| | - Susan Jack
- School of Nursing, McMaster University, Hamilton, Ontario, Canada
| | - Teresa Bennett
- Psychiatry and Behavioural Neuroscience, McMaster University, Hamilton, Ontario, Canada
- Offord Centre for Child Studies, McMaster University, Hamilton, Ontario, Canada
| | - Sandeep Raha
- Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Eric Duku
- Offord Centre for Child Studies, McMaster University, Hamilton, Ontario, Canada
| | - Andrea Gonzalez
- Psychiatry and Behavioural Neuroscience, McMaster University, Hamilton, Ontario, Canada
- Offord Centre for Child Studies, McMaster University, Hamilton, Ontario, Canada
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Lee JJ, Flouri E. The relationship between diurnal cortisol slope and cognitive development among children maltreated as infants. CHILDREN AND YOUTH SERVICES REVIEW 2023; 148:106873. [PMID: 36876149 PMCID: PMC9983686 DOI: 10.1016/j.childyouth.2023.106873] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Little is known about the role of hypothalamic-pituitary-adrenal (HPA) axis functioning for children's cognitive development, especially among vulnerable groups. The current study explores the relationship between diurnal cortisol slope and cognitive outcomes among children at the ages of 5 and 6 who have been maltreated as infants and involved with child protective services, using data from the National Survey of Child and Adolescent Well-Being (NSCAW) I (N=158). Multiple regression analyses showed that a greater decline in salivary cortisol from morning to evening was positively associated with scores on applied problems and expressive communication, even after adjustment for confounding. It was also associated with lower odds of cognitive disability. There were null associations with letter-word identification, passage comprehension, auditory comprehension, matrices, and vocabulary. Results suggest that children involved with child protective services as infants, and thus exposed early to likely 'toxic' levels of stressors, may face dysregulation of the HPA axis and particular difficulties in some aspects of cognitive function. Potential explanations and implications for policy are discussed.
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Affiliation(s)
- Jane Jiyoun Lee
- Child Maltreatment Solutions Network, Social Science Research Institute, Pennsylvania State University, 202 Henderson Building, University Park, PA, 16802
| | - Eirini Flouri
- Department of Psychology and Human Development, UCL Institute of Education, University College London, 20 Bedford, Way, London, WC1H 0AL
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Martín-González NS, Castro-Quintas Á, Marques-Feixa L, Ayesa-Arriola R, López M, Fañanás L. Maternal respiratory viral infections during pregnancy and offspring's neurodevelopmental outcomes: a systematic review. Neurosci Biobehav Rev 2023; 149:105178. [PMID: 37059407 DOI: 10.1016/j.neubiorev.2023.105178] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 03/18/2023] [Accepted: 04/11/2023] [Indexed: 04/16/2023]
Abstract
Maternal infections during pregnancy, as cytomegalovirus and zika, have been consistently associated with severe newborn neurodevelopmental conditions, mainly related to vertical transmission and congenital infection. However, little is known about the neurodevelopmental consequences of maternal respiratory viral infections, which are the most prevalent infections during pregnancy. The recent COVID-19 pandemic has increased the interest in understanding the consequences of infections in offspring's development. This systematic review explores whether maternal gestational viral respiratory infections are associated with neurodevelopmental deviations in children below 10 years-old. The search was conducted in Pubmed, PsychInfo and Web of Science databases. 12 articles were revised, including information about maternal infection (Influenza, SARS-CoV-2 and unspecified respiratory infections) and offspring's neurodevelopment (global development, specific functions, temperament and behavioral/emotional aspects). Controversial results were reported regarding maternal respiratory infections during pregnancy and infants' neurodevelopment. Maternal infections seem to be associated with subtle alterations in some offspring's developmental subdomains, as early motor development, and attentional, behavioral/emotional minor problems. Further studies are needed to determine the impact of other psychosocial confounding factors.
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Affiliation(s)
- Nerea San Martín-González
- Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Barcelona, Spain; Network Centre for Biomedical Research in Mental Health (CIBER of Mental Health, CIBER-SAM), Madrid, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
| | - Águeda Castro-Quintas
- Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Barcelona, Spain; Network Centre for Biomedical Research in Mental Health (CIBER of Mental Health, CIBER-SAM), Madrid, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
| | - Laia Marques-Feixa
- Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Barcelona, Spain; Network Centre for Biomedical Research in Mental Health (CIBER of Mental Health, CIBER-SAM), Madrid, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
| | - Rosa Ayesa-Arriola
- Network Centre for Biomedical Research in Mental Health (CIBER of Mental Health, CIBER-SAM), Madrid, Spain; Department of Psychiatry, School of Medicine, University of Cantabria, University Hospital Marqués de Valdecilla, Santander, Spain; IDIVAL, Valdecilla Biomedical Research Institute, Santander, Spain.
| | - Marta López
- Fetal Medicine Research Center, Maternal fetal medicine department, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Centre for Biomedical Research on Rare Diseases (CIBER of Rare Diseases, CIBER-ER), Madrid, Spain.
| | - Lourdes Fañanás
- Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Barcelona, Spain; Network Centre for Biomedical Research in Mental Health (CIBER of Mental Health, CIBER-SAM), Madrid, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
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Liu MY, Wei LL, Zhu XH, Ding HC, Liu XH, Li H, Li YY, Han Z, Li LD, Du ZW, Zhou YP, Zhang J, Meng F, Tang YL, Liu X, Wang C, Zhou QG. Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor. Mol Psychiatry 2023; 28:1383-1395. [PMID: 36481932 PMCID: PMC10005958 DOI: 10.1038/s41380-022-01898-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 11/18/2022] [Indexed: 12/13/2022]
Abstract
In response to stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, and consequently glucocorticoids are released by the adrenal gland into the blood circulation. A large body of research has illustrated that excessive glucocorticoids in the hippocampus exerts negative feedback regulation of the HPA axis through glucocorticoid receptor (GR), which is critical for the homeostasis of the HPA axis. Maternal prenatal stress causes dysfunction of the HPA axis feedback mechanism in their offspring in adulthood. Here we report that telomerase reverse transcriptase (TERT) gene knockout causes hyperactivity of the HPA axis without hippocampal GR deficiency. We found that the level of TERT in the dentate gyrus (DG) of the hippocampus during the developmental stage determines the responses of the HPA axis to stressful events in adulthood through modulating the excitability of the dentate granular cells (DGCs) rather than the expression of GR. Our study also suggests that the prenatal high level of glucocorticoids exposure-induced hypomethylation at Chr13:73764526 in the first exon of mouse Tert gene accounted for TERT deficiency in the DG and HPA axis abnormality in the adult offspring. This study reveals a novel GR-independent mechanism underlying prenatal stress-associated HPA axis impairment, providing a new angle for understanding the mechanisms for maintaining HPA axis homeostasis.
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Affiliation(s)
- Meng-Ying Liu
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China.,Department of Pharmacy, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Lu-Lu Wei
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China
| | - Xian-Hui Zhu
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China.,Department of Clinical Pharmacy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Hua-Chen Ding
- Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
| | - Xiang-Hu Liu
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China
| | - Huan Li
- School of Applied Science, Temasek Polytechnic, Singapore, Singapore.,College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuan-Yuan Li
- Department of Clinical Pharmacy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Zhou Han
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China.,Department of Pharmacy, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Lian-Di Li
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China
| | - Zi-Wei Du
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China
| | - Ya-Ping Zhou
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China
| | - Jing Zhang
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China
| | - Fan Meng
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China
| | - Yu-Lin Tang
- Department of Clinical Pharmacy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Xiao Liu
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
| | - Chun Wang
- Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China.
| | - Qi-Gang Zhou
- State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China. .,Department of Clinical Pharmacy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China. .,Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China. .,The Key Center of Gene Technology Drugs of Jiangsu Province, Nanjing Medical University, Nanjing, China.
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12
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Weiss SJ, Keeton V, Richoux S, Cooper B, Niemann S. Exposure to antenatal corticosteroids and infant cortisol regulation. Psychoneuroendocrinology 2023; 147:105960. [PMID: 36327758 PMCID: PMC9968454 DOI: 10.1016/j.psyneuen.2022.105960] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 09/16/2022] [Accepted: 10/23/2022] [Indexed: 11/06/2022]
Abstract
Administration of antenatal corticosteroids (AC) is the standard of care during pregnancy for women who are at risk of early delivery. Evidence indicates that AC improve survival and reduce morbidity for preterm infants. However, research suggests that infants whose mothers receive AC have an altered hypothalamic-pituitary-axis (HPA) response to stressors in early life. Results are mixed regarding the nature of these effects, with studies showing both suppressed and augmented HPA activity. In addition, research is very limited beyond the 4th month of life. The purpose of this study was to determine if AC exposure was associated with infant cortisol levels in a resting state or in response to a stressor at 1, 6 and 12 months postnatal. We also evaluated the moderating role of preterm birth in this association. 181 women and their infants participated in the study. Women were recruited during the 3rd trimester of pregnancy; at this time, they completed the Perceived Stress Scale and provided 8 salivary samples over a 2-day period for cortisol assay. They provided these data again at 6 and 12 months postnatal. At 1, 6, and 12 months postnatal, salivary samples were collected from infants to examine their cortisol levels before and after participation in a 'stressor protocol'. Data were extracted from the medical record on AC exposure, gestational age, maternal obstetric risk, and neonatal morbidity. Mixed effects multilevel regression modeling was used to examine the aims. Infants whose mothers received AC had significantly lower resting state (B = -2.47, CI: -3.691, -0.0484) and post-stressor (B = -2.51, CI: -4.283, -0.4276) cortisol levels across the first year of life than infants whose mothers did not receive AC. There was no moderating effect of preterm birth on the relationship between AC exposure and cortisol. Results indicate a state of dampened HPA activation and cortisol hypo-arousal that persists across the first year of life among infants who were exposed to corticosteroids in utero. Further research is needed to examine mechanisms responsible for any alterations that occur during development of the fetal HPA axis, including epigenetic and biochemical factors that control hormonal secretion, negative feedback, and glucocorticoid receptor function throughout the HPA axis. Findings warrant careful consideration by obstetric clinicians of the benefits and risks of prescribing AC.
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Affiliation(s)
- Sandra J. Weiss
- Department of Community Health Systems, University of California, San Francisco, USA,Correspondence to: Department of Community Health Systems, University of California, Box 0608, 2 Koret Way, San Francisco, CA, 94143, USA. (S.J. Weiss)
| | - Victoria Keeton
- Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, USA
| | - Sarah Richoux
- Department of Community Health Systems, University of California, San Francisco, USA
| | - Bruce Cooper
- Department of Community Health Systems, University of California, San Francisco, USA
| | - Sandra Niemann
- Department of Community Health Systems, University of California, San Francisco, USA
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13
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Sapsford TP, Johnson SR, Headrick JP, Branjerdporn G, Adhikary S, Sarfaraz M, Stapelberg NJC. Forgetful, sad and old: Do vascular cognitive impairment and depression share a common pre-disease network and how is it impacted by ageing? J Psychiatr Res 2022; 156:611-627. [PMID: 36372004 DOI: 10.1016/j.jpsychires.2022.10.071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 10/25/2022] [Accepted: 10/31/2022] [Indexed: 11/07/2022]
Abstract
Vascular cognitive impairment (VCI) and depression frequently coexist in geriatric populations and reciprocally increase disease risks. We assert that a shared pre-disease state of the psycho-immune-neuroendocrine (PINE) network model mechanistically explains bidirectional associations between VCI and depression. Five pathophysiological sub-networks are identified that are shared by VCI and depression: neuroinflammation, kynurenine pathway imbalance, hypothalamic-pituitary-adrenal (HPA) axis overactivity, impaired neurotrophic support and cerebrovascular dysfunction. These do not act independently, and their complex interactions necessitate a systems biology approach to better define disease pathogenesis. The PINE network is already established in the context of non-communicable diseases (NCDs) such as depression, hypertension, atherosclerosis, coronary heart disease and type 2 diabetes mellitus. We build on previous literature to specifically explore mechanistic links between MDD and VCI in the context of PINE pathways and discuss key mechanistic commonalities linking these comorbid conditions and identify a common pre-disease state which precedes transition to VCI and MDD. We expand the model to incorporate bidirectional interactions with biological ageing. Diathesis factors for both VCI and depression feed into this network and the culmination of shared mechanisms (on an ageing substrate) lead to a critical network transition to one or both disease states. A common pre-disease state underlying VCI and depression can provide clinicians a unique opportunity for early risk assessment and intervention in disease development. Establishing the mechanistic elements and systems biology of this network can reveal early warning or predictive biomarkers together with novel therapeutic targets. Integrative studies are recommended to elucidate the dynamic networked biology of VCI and depression over time.
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Affiliation(s)
- Timothy P Sapsford
- Griffith University School of Medicine, Gold Coast, Queensland, Australia; Gold Coast Hospital and Health Service, Gold Coast, Queensland, Australia
| | - Susannah R Johnson
- Gold Coast Hospital and Health Service, Gold Coast, Queensland, Australia
| | - John P Headrick
- Griffith University School of Medicine, Gold Coast, Queensland, Australia
| | - Grace Branjerdporn
- Gold Coast Hospital and Health Service, Gold Coast, Queensland, Australia.
| | - Sam Adhikary
- Mater Young Adult Health Centre, Mater Hospital, Brisbane, Queensland, Australia
| | - Muhammad Sarfaraz
- Gold Coast Hospital and Health Service, Gold Coast, Queensland, Australia
| | - Nicolas J C Stapelberg
- Gold Coast Hospital and Health Service, Gold Coast, Queensland, Australia; Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia
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14
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Ayeni EA, Aldossary AM, Ayejoto DA, Gbadegesin LA, Alshehri AA, Alfassam HA, Afewerky HK, Almughem FA, Bello SM, Tawfik EA. Neurodegenerative Diseases: Implications of Environmental and Climatic Influences on Neurotransmitters and Neuronal Hormones Activities. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph191912495. [PMID: 36231792 PMCID: PMC9564880 DOI: 10.3390/ijerph191912495] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/21/2022] [Accepted: 09/24/2022] [Indexed: 05/23/2023]
Abstract
Neurodegenerative and neuronal-related diseases are major public health concerns. Human vulnerability to neurodegenerative diseases (NDDs) increases with age. Neuronal hormones and neurotransmitters are major determinant factors regulating brain structure and functions. The implications of environmental and climatic changes emerged recently as influence factors on numerous diseases. However, the complex interaction of neurotransmitters and neuronal hormones and their depletion under environmental and climatic influences on NDDs are not well established in the literature. In this review, we aim to explore the connection between the environmental and climatic factors to NDDs and to highlight the available and potential therapeutic interventions that could use to improve the quality of life and reduce susceptibility to NDDs.
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Affiliation(s)
- Emmanuel A. Ayeni
- Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ahmad M. Aldossary
- National Center of Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 12354, Saudi Arabia
| | - Daniel A. Ayejoto
- Department of Industrial Chemistry, University of Ilorin, Ilorin 240003, Nigeria
| | - Lanre A. Gbadegesin
- University of Chinese Academy of Sciences, Beijing 100049, China
- Institute of Mountain Hazards and Environment, Chinese Academy of Sciences, Chengdu 610041, China
| | - Abdullah A. Alshehri
- National Center of Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 12354, Saudi Arabia
| | - Haya A. Alfassam
- KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh 12354, Saudi Arabia
| | - Henok K. Afewerky
- Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
- School of Allied Health Professions, Asmara College of Health Sciences, Asmara P.O. Box 1220, Eritrea
| | - Fahad A. Almughem
- National Center of Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 12354, Saudi Arabia
| | - Saidu M. Bello
- Institute of Pharmacognosy, University of Szeged, 6720 Szeged, Hungary
| | - Essam A. Tawfik
- National Center of Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 12354, Saudi Arabia
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15
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Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: when timing matters. Transl Psychiatry 2022; 12:386. [PMID: 36114180 PMCID: PMC9481531 DOI: 10.1038/s41398-022-02160-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/02/2022] [Accepted: 09/07/2022] [Indexed: 11/27/2022] Open
Abstract
Stress exposure during pregnancy is critically linked with maternal mental health and child development. The effects might involve altered patterns of DNA methylation in specific stress-related genes (i.e., glucocorticoid receptor gene, NR3C1, and serotonin transporter gene, SLC6A4) and might be moderated by the gestational timing of stress exposure. In this study, we report on NR3C1 and SLC6A4 methylation status in Italian mothers and infants who were exposed to the COVID-19 pandemic lockdown during different trimesters of pregnancy. From May 2020 to February 2021, 283 mother-infant dyads were enrolled at delivery. Within 24 h from delivery, buccal cells were collected to assess NR3C1 (44 CpG sites) and SLC6A4 (13 CpG sites) methylation status. Principal component (PC) analyses were used to reduce methylation data dimension to one PC per maternal and infant gene methylation. Mother-infant dyads were split into three groups based on the pregnancy trimester (first, second, third), during which they were exposed to the COVID-19 lockdown. Mothers and infants who were exposed to the lockdown during the first trimester of pregnancy had lower NR3C1 and SLC6A4 methylation when compared to counterparts exposed during the second or third trimesters. The effect remained significant after controlling for confounders. Women who were pregnant during the pandemic and their infants might present altered epigenetic biomarkers of stress-related genes. As these epigenetic marks have been previously linked with a heightened risk of maternal psychiatric problems and less-than-optimal child development, mothers and infants should be adequately monitored for psychological health during and after the pandemic.
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16
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Wu S, Chen N, Tong X, Xu X, Chen Q, Wang F. Selenium attenuates the cadmium-induced placenta glucocorticoid barrier damage by up-regulating the expression of specificity protein 1. J Biochem Mol Toxicol 2022; 36:e23056. [PMID: 35384129 DOI: 10.1002/jbt.23056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 01/26/2022] [Accepted: 03/02/2022] [Indexed: 11/09/2022]
Abstract
Cadmium (Cd) is an environmental pollutant and pregnant women are especially susceptible to the effects of exposure to Cd. Our previous study found Cd can be accumulated in the placenta and causes fetal growth restriction (FGR) through damage the placental glucocorticoid barrier. Selenium (Se), as an essential micronutrient, can allivate Cd-induced toxicity. In this study, we aim to explore the protective mechanism of Se against Cd-induced the placental glucocorticoid barrier damage and FGR. Pregnant Sprague Dawley (SD) rats were exposed to CdCl2 (1 mg/kg/day) and Na2 SeO3 (0.1-0.2-0.3 mg/kg/day) by gavage from gestational day (GD) 0 to GD 19. The results showed that reduced fetal weight, increased corticosterone concentrations in the maternal and fetal serum, and impaired placental labyrinth layer blood vessel development, appeared in pregnant rats after Cd exposure and improved after treated with Se. In cell experiments, we confirmed that Se reduces Cd-induced apoptosis. Moreover, Se can abolish Cd-induced 11β-HSD2 and specificity protein 1 (Sp1) decreasing in vivo and vitro. In human JEG-3 cells, the knockdown of Sp1 expression by small interfering RNA can suppressed the protective effect of Se on Cd-induced 11β-HSD2 decreasing. In general, our results demonstrated that Se is resistant to Cd-induced FGR through upregulating the placenta barrier via activation of the transcription factor Sp1.
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Affiliation(s)
- Sisi Wu
- Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Na Chen
- Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xia Tong
- Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xu Xu
- Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qihui Chen
- Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Fan Wang
- Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
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17
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Vautier AN, Cadaret CN. Long-Term Consequences of Adaptive Fetal Programming in Ruminant Livestock. FRONTIERS IN ANIMAL SCIENCE 2022. [DOI: 10.3389/fanim.2022.778440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Environmental perturbations during gestation can alter fetal development and postnatal animal performance. In humans, intrauterine growth restriction (IUGR) resulting from adaptive fetal programming is known as a leading cause of perinatal morbidity and mortality and predisposes offspring to metabolic disease, however, the prevalence and impact in livestock is not characterized as well. Multiple animal models have been developed as a proxy to determine mechanistic changes that underlie the postnatal phenotype resulting from these programming events in humans but have not been utilized as robustly in livestock. While the overall consequences are similar between models, the severity of the conditions appear to be dependent on type, timing, and duration of insult, indicating that some environmental insults are of more relevance to livestock production than others. Thus far, maternofetal stress during gestation has been shown to cause increased death loss, low birth weight, inefficient growth, and aberrant metabolism. A breadth of this data comes from the fetal ruminant collected near term or shortly thereafter, with fewer studies following these animals past weaning. Consequently, even less is known about how adaptive fetal programming impacts subsequent progeny. In this review, we summarize the current knowledge of the postnatal phenotype of livestock resulting from different models of fetal programming, with a focus on growth, metabolism, and reproductive efficiency. We further describe what is currently known about generational impacts of fetal programming in production systems, along with gaps and future directions to consider.
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18
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The Impact of Maternal Prenatal Stress Related to the COVID-19 Pandemic during the First 1000 Days: A Historical Perspective. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19084710. [PMID: 35457577 PMCID: PMC9029063 DOI: 10.3390/ijerph19084710] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 03/26/2022] [Accepted: 03/30/2022] [Indexed: 12/12/2022]
Abstract
The COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable members, including pregnant women and their unborn children. Pregnant mothers reported fear of infection, fear of vertical transmission, fear of poor birth and child outcomes, social isolation, uncertainty about their partner's presence during medical appointments and delivery, increased domestic abuse, and other collateral damage, including vaccine hesitancy. Accordingly, pregnant women's known vulnerability for mental health problems has become a concern during the COVID-19 pandemic, also because of the known effects of prenatal stress for the unborn child. The current narrative review provides a historical overview of transgenerational effects of exposure to disasters during pregnancy, and the role of maternal prenatal stress. We place these effects into the perspective of the COVID-19 pandemic. Hereby, we aim to draw attention to the psychological impact of the COVID-19 pandemic on women of reproductive age (15-49 year) and its potential associated short-term and long-term consequences for the health of children who are conceived, carried, and born during this pandemic. Timely detection and intervention during the first 1000 days is essential to reduce the burden of transgenerational effects of the COVID-19 pandemic.
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19
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Oxytocin receptor genotype moderates the association between maternal prenatal stress and infant early self-regulation. Psychoneuroendocrinology 2022; 138:105669. [PMID: 35063684 DOI: 10.1016/j.psyneuen.2022.105669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 12/22/2021] [Accepted: 01/12/2022] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Maternal prenatal stress may have long-term adverse consequences for child development. Accumulating evidence shows that the oxytocin-receptor genotype may play a role in differential susceptibility to early-life adversity, but no studies have examined whether this moderation extends to the prenatal stress exposures. METHODS In the FinnBrain Birth Cohort Study, a sample of 1173 mother-child dyads were examined. We studied the possible moderating effect of the cumulative effect of infant oxytocin-receptor risk genotypes (rs53576GG and rs2254298A) in the association between maternal prenatal stress, and infant negative reactivity and emerging self-regulation at 6 months of age. RESULTS The number of OTr risk genotypes moderated the association between maternal prenatal anxiety and infant self-regulation, implying a cumulative effect of genotype, although effects sizes were small. In infants with two risk genotypes, a negative association between prenatal anxiety and self-regulation was observed, whereas in infants with one or no risk genotypes, the association between maternal prenatal anxiety and temperament was non-significant. CONCLUSION Oxytocin-receptor genotype may moderate the association of maternal stress during pregnancy and child social-emotional development. Possible mechanisms for this moderation effect are discussed. Further studies with a more comprehensive polygenic approach are needed to confirm these results.
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20
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Hamilton CM, Winter MJ, Margiotta-Casaluci L, Owen SF, Tyler CR. Are synthetic glucocorticoids in the aquatic environment a risk to fish? ENVIRONMENT INTERNATIONAL 2022; 162:107163. [PMID: 35240385 DOI: 10.1016/j.envint.2022.107163] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 05/27/2023]
Abstract
The glucocorticosteroid, or glucocorticoid (GC), system is largely conserved across vertebrates and plays a central role in numerous vital physiological processes including bone development, immunomodulation, and modification of glucose metabolism and the induction of stress-related behaviours. As a result of their wide-ranging actions, synthetic GCs are widely prescribed for numerous human and veterinary therapeutic purposes and consequently have been detected extensively within the aquatic environment. Synthetic GCs designed for humans are pharmacologically active in non-mammalian vertebrates, including fish, however they are generally detected in surface waters at low (ng/L) concentrations. In this review, we assess the potential environmental risk of synthetic GCs to fish by comparing available experimental data and effect levels in fish with those in mammals. We found the majority of compounds were predicted to have insignificant risk to fish, however some compounds were predicted to be of moderate and high risk to fish, although the dataset of compounds used for this analysis was small. Given the common mode of action and high level of inter-species target conservation exhibited amongst the GCs, we also give due consideration to the potential for mixture effects, which may be particularly significant when considering the potential for environmental impact from this class of pharmaceuticals. Finally, we also provide recommendations for further research to more fully understand the potential environmental impact of this relatively understudied group of commonly prescribed human and veterinary drugs.
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Affiliation(s)
- Charles M Hamilton
- Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, Devon EX4 4QD, UK
| | - Matthew J Winter
- Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, Devon EX4 4QD, UK
| | - Luigi Margiotta-Casaluci
- Department of Analytical, Environmental & Forensic Sciences, School of Cancer & Pharmaceutical Sciences, King's College London, London SE1 9NH, UK
| | - Stewart F Owen
- AstraZeneca, Global Environment, Macclesfield, Cheshire SK10 2NA, UK
| | - Charles R Tyler
- Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, Devon EX4 4QD, UK.
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21
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Risk compounds, potential mechanisms and biomarkers of Traditional Chinese medicine‐induced reproductive toxicity. J Appl Toxicol 2022; 42:1734-1756. [DOI: 10.1002/jat.4290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 01/13/2022] [Accepted: 01/19/2022] [Indexed: 11/07/2022]
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22
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Mathewson KJ, McGowan PO, de Vega WC, Morrison KM, Saigal S, Van Lieshout RJ, Schmidt LA. Cumulative risks predict epigenetic age in adult survivors of extremely low birth weight. Dev Psychobiol 2021; 63 Suppl 1:e22222. [PMID: 34964497 DOI: 10.1002/dev.22222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 10/08/2021] [Accepted: 11/02/2021] [Indexed: 11/06/2022]
Abstract
Long-term sequelae of extremely low birth weight (ELBW; ≤1000 g) may contribute to accelerated biological aging. This hypothesis was examined by analyzing a range of risk factors with a molecular age marker in adults born at ELBW or normal birth weight (NBW; ≥2500 g). DNAm age-the weighted average of DNA methylation at 353 cytosine-phosphate-guanine (CpG) sites from across the genome-was derived from a sample of 45 ELBW (Mage = 32.35 years) and 47 NBW control (Mage = 32.44 years) adults, using the Illumina 850k BeadChip Array. At two assessments undertaken 9 years apart (at 23 and 32 years), cumulative risks were summed from six domains with potential to affect physiological and psychological health: resting respiratory sinus arrhythmia, blood pressure, basal cortisol, grip strength, body mass index, and self-esteem. At age 32 years, cumulative risks were differentially associated with epigenetic age in ELBW survivors (interaction, p < 0.01). For each additional risk factor they possessed, ELBW survivors (B = 1.43) were biologically 2.16 years older than NBW adults (B = -0.73), by the fourth decade of life. Developmental change, epigenetic maintenance, and intervention targets are discussed.
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Affiliation(s)
- Karen J Mathewson
- Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, Ontario, Canada
| | - Patrick O McGowan
- Department of Biological Sciences, Cell and Systems Biology, Psychology, and Physiology, University of Toronto, Toronto, Ontario, Canada
| | - Wilfred C de Vega
- Department of Biological Sciences, Cell and Systems Biology, Psychology, and Physiology, University of Toronto, Toronto, Ontario, Canada
| | | | - Saroj Saigal
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Ryan J Van Lieshout
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
| | - Louis A Schmidt
- Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, Ontario, Canada
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Dufford AJ, Spann M, Scheinost D. How prenatal exposures shape the infant brain: Insights from infant neuroimaging studies. Neurosci Biobehav Rev 2021; 131:47-58. [PMID: 34536461 DOI: 10.1016/j.neubiorev.2021.09.017] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/30/2021] [Accepted: 09/12/2021] [Indexed: 10/20/2022]
Abstract
Brain development during the prenatal period is rapid and unparalleled by any other time during development. Biological systems undergoing rapid development are at higher risk for disorganizing influences. Therefore, certain prenatal exposures impact brain development, increasing risk for negative neurodevelopmental outcome. While prenatal exposures have been associated with cognitive and behavioral outcomes later in life, the underlying macroscopic brain pathways remain unclear. Here, we review magnetic resonance imaging (MRI) studies investigating the association between prenatal exposures and infant brain development focusing on prenatal exposures via maternal physical health factors, maternal mental health factors, and maternal drug and medication use. Further, we discuss the need for studies to consider multiple prenatal exposures in parallel and suggest future directions for this body of research.
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Affiliation(s)
| | - Marisa Spann
- Columbia University Irving Medical Center, 622 West 168th Street, New York, NY, 10032, USA
| | - Dustin Scheinost
- Child Study Center, Yale School of Medicine, New Haven, CT, USA; Department of Radiology and Biomedical Imaging, Yale School of Medicine, USA; Department of Statistics and Data Science, Yale University, New Haven, CT, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA
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24
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Polat S, Caner A. TRANSGENERATIONAL IMPACT OF TOPICAL STEROID APPLICATION ON SUPEROXIDE DISMUTASE ACTIVITIES OF HYPOTHALAMUS-PITUITARY-ADRENAL AXIS IN RATS. Can J Physiol Pharmacol 2021; 100:386-392. [PMID: 34826257 DOI: 10.1139/cjpp-2021-0493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Topical steroids(TS) are widely prescribed since the 1950s.This study aimed to investigate the transgenerational effects of TS on the antioxidant mechanism of the hypothalamus-pituitary-adrenal(HPA) axis,both in prenatal and infancy for the first time. Three generations(F1, F2 and F3) and prenatal group(P) were investigated in both sexes with two different time points; P45th and P75th day were accepted as puberty and early adulthood,respectively.Clobetasol propionate 0.05% was used as TS.qRT-PCR was performed to expressional analyses of Sod1, Sod2, and Sod3 genes in the HPA tissues. The Sods mRNA expression of the HPA belonging to P and F1 groups revealed similar results in both genders. The downregulation in the adrenal Sod level was determined in P and F1, F2, and F3 generations in both gender, especially in females(p<0.05).Sods activities in the pituitary of all groups were downregulated in female rats(p<0.05).Interestingly,in male rats,Sod2 and Sod3 weren't expressed in the pituitary compare to control on the day P45 while Sod2 and Sod3 expressions were determined in all the groups on the day P75.Sod1 overexpression found in pituitary and hypothalamus of male in F3 generation. This study showed that TS applied in infancy had a transgenerational adverse effect on antioxidant defense mechanisms especially in the adrenal.
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Affiliation(s)
- Seher Polat
- Erzincan University, 162315, Medical Genetics, Basbaglar Mah, Erzincan, Turkey, 24100;
| | - Armağan Caner
- Erciyes Universitesi Tip Fakultesi, 64212, Biophysics, Kayseri, Kayseri, Turkey;
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25
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McDonald SE, Tomlinson CA, Applebaum JW, Moyer SW, Brown SM, Carter S, Kinser PA. Human-Animal Interaction and Perinatal Mental Health: A Narrative Review of Selected Literature and Call for Research. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:10114. [PMID: 34639416 PMCID: PMC8508333 DOI: 10.3390/ijerph181910114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 12/13/2022]
Abstract
There is a paucity of research exploring how relationships with household pets may impact maternal mental health. We are unaware of any study to date that has examined associations between individuals' relationships with their pets and psychological adjustment in the perinatal period. Using a biobehavioral lens, this paper provides a narrative overview of the literature on perinatal mental health and human-animal interaction (HAI). We focus on the role of social relationships, stress, and stress reduction in relation to perinatal mental health; the role of HAI in perceptions of social support, stressors, and stress reduction; and gaps in empirical knowledge concerning the role of HAI in perinatal mental health. Finally, we integrate contemporary biobehavioral models of perinatal mental health and HAI (i.e., Comprehensive Model of Mental Health during the Perinatal Period and the HAI-HPA Transactional Model) to propose a new conceptual framework that depicts ways in which HAI during the perinatal period may influence maternal and child health and wellbeing. To our knowledge, this is the first paper to consider the role of HAI in biobehavioral responses and mental health during the perinatal period. We conclude with recommendations for future research and improved perinatal care.
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Affiliation(s)
- Shelby E. McDonald
- Children, Families, and Animals Research (CFAR) Group, LLC, Richmond, VA 23223, USA
| | - Camie A. Tomlinson
- School of Social Work, Virginia Commonwealth University, Richmond, VA 23284, USA
| | - Jennifer W. Applebaum
- Department of Sociology and Criminology & Law, University of Florida, Gainesville, FL 32611, USA;
| | - Sara W. Moyer
- School of Nursing, Virginia Commonwealth University, Richmond, VA 23298, USA; (S.W.M.); (P.A.K.)
| | - Samantha M. Brown
- School of Social Work, Colorado State University, Fort Collins, CO 80523, USA;
| | - Sue Carter
- The Kinsey Institute, Indiana University, Bloomington, IN 47405, USA;
| | - Patricia A. Kinser
- School of Nursing, Virginia Commonwealth University, Richmond, VA 23298, USA; (S.W.M.); (P.A.K.)
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26
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Westrick SE, van Kesteren F, Boutin S, Lane JE, McAdam AG, Dantzer B. Maternal glucocorticoids have minimal effects on HPA axis activity and behavior of juvenile wild North American red squirrels. J Exp Biol 2021; 224:jeb.236620. [PMID: 33795416 DOI: 10.1242/jeb.236620] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 03/29/2021] [Indexed: 12/27/2022]
Abstract
As a response to environmental cues, maternal glucocorticoids (GCs) may trigger adaptive developmental plasticity in the physiology and behavior of offspring. In North American red squirrels (Tamiasciurus hudsonicus), mothers exhibit increased GCs when conspecific density is elevated, and selection favors more aggressive and perhaps more active mothers under these conditions. We tested the hypothesis that elevated maternal GCs cause shifts in offspring behavior that may prepare them for high-density conditions. We experimentally elevated maternal GCs during gestation or early lactation. We measured two behavioral traits (activity and aggression) in weaned offspring using standardized behavioral assays. Because maternal GCs may influence offspring hypothalamic-pituitary-adrenal (HPA) axis dynamics, which may in turn affect behavior, we also measured the impact of our treatments on offspring HPA axis dynamics (adrenal reactivity and negative feedback), and the association between offspring HPA axis dynamics and behavior. Increased maternal GCs during lactation, but not gestation, slightly elevated activity levels in offspring. Offspring aggression and adrenal reactivity did not differ between treatment groups. Male, but not female, offspring from mothers treated with GCs during pregnancy exhibited stronger negative feedback compared with those from control mothers, but there were no differences in negative feedback between lactation treatment groups. Offspring with higher adrenal reactivity from mothers treated during pregnancy (both controls and GC-treated) exhibited lower aggression and activity. These results suggest that maternal GCs during gestation or early lactation alone may not be a sufficient cue to produce substantial changes in behavioral and physiological stress responses in offspring in natural populations.
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Affiliation(s)
- Sarah E Westrick
- Department of Psychology, University of Michigan, Ann Arbor, MI48109-1043, USA
| | - Freya van Kesteren
- Department of Psychology, University of Michigan, Ann Arbor, MI48109-1043, USA
| | - Stan Boutin
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada, T6G 2E9
| | - Jeffrey E Lane
- Department of Biology, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5E2
| | - Andrew G McAdam
- Ecology and Evolutionary Biology, University of Colorado, Boulder, CO 80309-0334, USA
| | - Ben Dantzer
- Department of Psychology, University of Michigan, Ann Arbor, MI48109-1043, USA.,Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109-1085, USA
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Zheng Y, Zhang YM, Tang ZS, Du JK, Guo DW, Xu YJ, Sheng H, Lu JQ, Ni X. Spatial learning and memory deficits induced by prenatal glucocorticoid exposure depend on hippocampal CRHR1 and CXCL5 signaling in rats. J Neuroinflammation 2021; 18:85. [PMID: 33810797 PMCID: PMC8019183 DOI: 10.1186/s12974-021-02129-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Accepted: 03/12/2021] [Indexed: 11/13/2022] Open
Abstract
Background Prenatal synthetic glucocorticoid (sGC) exposure increases the susceptibility to cognitive and affective disorders in postnatal life. We previously demonstrated that prenatal sGC exposure results in an increase in corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) expression in the hippocampus of rats, and CRHR1 is involved in synapse formation via regulation of C-X-C chemokine ligand 5 (CXCL5) in hippocampus. We sought to investigate that the roles of CRHR1 and CXCL5 in learning and memory impairment caused by prenatal sGC exposure. Methods Pregnant rats were administered with saline or dexamethasone (DEX) from gestational day (GD) 14 to GD21. DEX offspring at 2-day old were treated with saline and CRHR1 antagonists (antalarmin and CP154526) for 7 days. Some DEX offspring received intra-hippocampal injection of AAV9 carrying CXCL5 gene. Spatial learning and memory was assessed by Morris water maze test. Immunofluorescence analysis was applied to show synapsin I and PSD95 signals in hippocampus. Synapsin I and PSD95 protein level and CXCL5 concentration were determined by western blotting and ELISA, respectively. Organotypic hippocampal slice cultures were used to investigate the effect of DEX on CXCL5 production in vitro. Results Both male and female DEX offspring displayed impairment of spatial learning and memory in adulthood. Synapsin I and PSD95 signals and CXCL5 levels were decreased in DEX offspring. DEX offspring with antalarmin and CP154526 treatment showed improved spatial learning and memory. Antalarmin and CP154526 treatment increased synapsin I and PSD95 signals and CXCL5 concentration in hippocampus. Bilaterally hippocampal injection of AAV9 carrying CXCL5 gene improved the spatial learning and memory and increased CXCL5 concentration and synapsin I and PSD95 levels in hippocampus. DEX dose-dependently suppressed CXCL5 production in cultured hippocammpal slices, which was prevented by antalarmin treatment. Conclusion CRHR1 and CXCL5 signaling in the hippocampus are involved in spatial learning and memory deficits caused by prenatal DEX exposure. CRHR1 activation contributes to decreased CXCL5 production in hippocampus induced by prenatal DEX treatment. Our study provides a molecular basis of prenatal GC exposure programming spatial learning and memory.
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Affiliation(s)
- You Zheng
- Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, 410008, China.,Department of Physiology, Navy Medical University, Shanghai, 200433, China.,Laboratory of Cell Engineering, Institute of Biotechnology, Beijing, 100071, China
| | - Yan-Min Zhang
- Department of Physiology, Navy Medical University, Shanghai, 200433, China.,School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China
| | - Zheng-Shan Tang
- Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
| | - Jian-Kui Du
- Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
| | - De-Wei Guo
- Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, 410008, China
| | - Yong-Jun Xu
- Department of Physiology, Navy Medical University, Shanghai, 200433, China
| | - Hui Sheng
- Department of Physiology, Navy Medical University, Shanghai, 200433, China
| | - Jian-Qiang Lu
- School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China
| | - Xin Ni
- Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, 410008, China. .,Department of Physiology, Navy Medical University, Shanghai, 200433, China. .,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China.
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Lalonde C, Grandbois J, Khurana S, Murray A, Tharmalingam S, Tai TC. Late gestational exposure to dexamethasone and fetal programming of abnormal behavior in Wistar Kyoto rats. Brain Behav 2021; 11:e02049. [PMID: 33528889 PMCID: PMC8035474 DOI: 10.1002/brb3.2049] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 12/16/2020] [Accepted: 01/08/2021] [Indexed: 01/02/2023] Open
Abstract
INTRODUCTION Fetal programming was characterized a few decades ago, explaining the correlation of physiological phenotypes of offspring exposed to early-life stress. High acute or chronic prenatal stress can overwhelm the enzymatic placental barrier, inducing transcriptional changes in the fetus that can result in different adverse behavioral and physiological phenotypes. The current study investigates the impact of exposure to the synthetic glucocorticoid, dexamethasone, during late gestation on behavioral outcomes. METHODS Pregnant Wistar Kyoto rats were given daily subcutaneous injections from gestational days 15-21 of either dexamethasone (0.9% NaCl, 4% EtOH, 100 µg kg-1 day-1 ) or were physically manipulated as naïve controls. Pups were raised normally until 17 weeks of age and underwent the Porsolt swim task and elevated plus maze for depressive and anxiety-like behaviors, respectively. Neural tissue was preserved for genetic analysis using quantitative real-time polymerase chain reaction. RESULTS Statistical analyses show significant disruption of behavior and genetic profiles of offspring exposed to dexamethasone in-utero. Exposed animals spent more time immobile on the swim task and entered open arms of the elevated plus maze more often than their naïve counterparts. In the prefrontal cortex, there was a sex by treatment interaction on gene expression relevant to neural transmission in ryanodine receptor 2, as well as increased gene expression in SNAP25, COMT, and LSAMP in males prenatally exposed to dexamethasone compared with controls. Both dysregulated genes and behavior are linked to decreased anxiety and fear inhibition. CONCLUSION Our results indicate adult offspring exposed to dexamethasone in-utero have a tendency toward passive stress-coping strategies and an inhibition of anxiety on behavioral tasks. Methyltransferase activity, synaptic activity, and cellular processes were disrupted in the prefrontal cortices of these animals. Specifically, genes involved in emotional response pathways were overexpressed, supporting the link between the behavioral and genetic profiles. Combined, we determine that dexamethasone offspring have adaptive predispositions when faced with novel situations, with increased immobility in the swim task and increased exploration on the elevated plus maze.
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Affiliation(s)
- Christine Lalonde
- Biomolecular Sciences, Laurentian University, Sudbury, ON, Canada.,Division of Medical Sciences, Northern Ontario School of Medicine, Sudbury, ON, Canada
| | - Julie Grandbois
- Division of Medical Sciences, Northern Ontario School of Medicine, Sudbury, ON, Canada.,Department of Biology, Laurentian University, Sudbury, ON, Canada
| | - Sandhya Khurana
- Biomolecular Sciences, Laurentian University, Sudbury, ON, Canada
| | - Alyssa Murray
- Division of Medical Sciences, Northern Ontario School of Medicine, Sudbury, ON, Canada.,Department of Biology, Laurentian University, Sudbury, ON, Canada
| | - Sujeenthar Tharmalingam
- Biomolecular Sciences, Laurentian University, Sudbury, ON, Canada.,Division of Medical Sciences, Northern Ontario School of Medicine, Sudbury, ON, Canada.,Department of Biology, Laurentian University, Sudbury, ON, Canada.,Department of Chem/Biochem, Laurentian University, Sudbury, ON, Canada
| | - T C Tai
- Biomolecular Sciences, Laurentian University, Sudbury, ON, Canada.,Division of Medical Sciences, Northern Ontario School of Medicine, Sudbury, ON, Canada.,Department of Biology, Laurentian University, Sudbury, ON, Canada.,Department of Chem/Biochem, Laurentian University, Sudbury, ON, Canada
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29
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Iyasere OS, Oyetunji DE, Wheto M, Durosaro SO, Adigun TT, Muraina HA, Akinyemi OO, Daramola JO. Effect of acute heat stress on cognitive performance of chickens in a feed-related discriminant task. J Therm Biol 2021; 98:102914. [PMID: 34016341 DOI: 10.1016/j.jtherbio.2021.102914] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 03/16/2021] [Accepted: 03/16/2021] [Indexed: 10/21/2022]
Abstract
Little is known about immediate and long-lasting effect of acute heat stress on chicken cognition. Thirty-five, 9-week-old birds were trained to differentiate two cone colours; white (rewarded, R; with feed underneath) and black (unrewarded, UR; empty). The sixteen birds that learnt the task were randomly assigned to three temperature regimens (TR: 22-24 °C (control), 30-32 and 36-38 °C for 3h/day) for three consecutive days during which rectal (RT), wing (WT) and eye (ET) temperatures were monitored. After the 3 h of exposure, birds were allowed to rest for 1 h before the commencement of the discriminant task. The latencies to open the cones (R and UR) and proportion of cones opened were recorded. A long-lasting effect was tested a week after exposure to TR. TR had a significant effect on RT, WT and ET. The motivation to turn over R cones was weaker in birds exposed to 36-38 °C than birds exposed to 22-24 °C. Also, the proportion of R cones opened were fewer in birds that experienced TR of 36-38 °C compared to birds exposed to 22-24 °C and 30-32 °C specifically on two out of the three cognitive test days (Days 1 and 3). Latency and proportion of UR cones opened was not affected by TR. RT, WT and ET were all negatively and significantly correlated with latency to open the UR cones. Previous exposure of birds to three TR had no effect on the latency to open both cones but the proportion of R cones opened was greater in birds exposed to 30-32 °C compared to the 22-24 °C birds. In conclusion, an immediate (36-38 °C) and long-lasting effect (30-32 °C) of acute heat stress was associated with a weak motivation to perform feed related discrimination task.
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Affiliation(s)
- Oluwaseun S Iyasere
- Department of Animal Physiology, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria.
| | - Damilola E Oyetunji
- Department of Animal Physiology, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Mathew Wheto
- Department of Animal Breeding and Genetics, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Samuel O Durosaro
- Department of Animal Breeding and Genetics, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Taiwo T Adigun
- Department of Animal Physiology, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Habeeb A Muraina
- Department of Animal Physiology, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Olaoluwa O Akinyemi
- Department of Animal Physiology, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - James O Daramola
- Department of Animal Physiology, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
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30
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Antenatal corticosteroids for impending late preterm (34-36+6 weeks) deliveries-A systematic review and meta-analysis of RCTs. PLoS One 2021; 16:e0248774. [PMID: 33750966 PMCID: PMC7984612 DOI: 10.1371/journal.pone.0248774] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 03/04/2021] [Indexed: 01/24/2023] Open
Abstract
Background Administration of antenatal corticosteroids (ANC) for impending preterm delivery beyond 34 weeks of gestation continues to be a controversial issue despite various guidelines for obstetricians and gynaecologists. Objective To compare outcomes following exposure to ANC for infants born between 34–36+6 weeks’ gestation. Methods A systematic review of randomised controlled trials (RCT) reporting neonatal outcomes after ANC exposure between 34–36+6 weeks’ gestation using Cochrane methodology. Databases including PubMed, Embase, Emcare, Cochrane Central library and Google Scholar were searched in May 2020. Primary outcomes: (1) Need for respiratory support (Mechanical ventilation, CPAP, high flow) or oxygen (2) Hypoglycemia. Secondary outcomes included respiratory distress syndrome (RDS), transient tachypnoea of newborn (TTN), need for neonatal resuscitation at birth [only in the delivery room immediately after birth (not in neonatal intensive care unit (NICU)], admission to NICU, mortality and developmental follow up. Level of evidence (LOE) was summarised by GRADE guidelines. Main results Seven RCTs (N = 4144) with low to high risk of bias were included. Only one RCT was from high income countries, Meta-analysis (random-effects model) showed (1) reduced need for respiratory support [5 RCTs (N = 3844); RR = 0.68 (0.47–0.98), p = 0.04; I2 = 55%; LOE: Moderate] and (2) higher risk of neonatal hypoglycaemia [4 RCTs (N = 3604); RR = 1.61(1.38–1.87), p<0.00001; I2 = 0%; LOE: High] after ANC exposure. Neonates exposed to ANC had reduced need for resuscitation at birth. The incidence of RDS, TTN and surfactant therapy did not differ significantly. None of the included studies reported long-term developmental follow up. Conclusions Moderate quality evidence indicates that ANC exposure reduced need for respiratory support, and increased the risk of hypoglycaemia in late preterm neonates. Large definitive trials with adequate follow up for neurodevelopmental outcomes are required to assess benefits and risks of ANC in this population.
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31
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Irwin JL, Meyering AL, Peterson G, Glynn LM, Sandman CA, Hicks LM, Davis EP. Maternal prenatal cortisol programs the infant hypothalamic-pituitary-adrenal axis. Psychoneuroendocrinology 2021; 125:105106. [PMID: 33340919 PMCID: PMC9743740 DOI: 10.1016/j.psyneuen.2020.105106] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 12/07/2020] [Accepted: 12/08/2020] [Indexed: 12/15/2022]
Abstract
One of the key proposed agents of fetal programming is exposure to maternal glucocorticoids. Experimental animal studies provide evidence that prenatal exposure to elevated maternal glucocorticoids has consequences for hypothalamic-pituitary-adrenal (HPA) axis functioning in the offspring. There are very few direct tests of maternal glucocorticoids, such as cortisol, during human pregnancy and associations with infant cortisol reactivity. The current study examined the link between maternal prenatal cortisol trajectories and infant cortisol reactivity to the pain of inoculation in a sample of 152 mother-infant (47.4% girls) pairs. The results from the current study provide insight into fetal programming of the infant HPA axis, demonstrating that elevated prenatal maternal cortisol is associated with a larger infant cortisol response to challenge at both 6 and 12 months of age.
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Affiliation(s)
- Jessica L Irwin
- Department of Psychology, University of La Verne, La Verne, CA 91750, United States; Department of Psychology, Chapman University, Orange, CA 92866, United States.
| | - Amy L Meyering
- Department of Psychology, University of Denver, Denver, CO 80208, United States
| | - Gage Peterson
- Department of Psychology, Chapman University, Orange, CA 92866, United States
| | - Laura M Glynn
- Department of Psychology, Chapman University, Orange, CA 92866, United States; Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697, United States
| | - Curt A Sandman
- Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697, United States
| | - Laurel M Hicks
- Renée Crown Wellness Institute, University of Colorado, Boulder, CO 80302, United States
| | - Elysia Poggi Davis
- Department of Psychology, University of Denver, Denver, CO 80208, United States; Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697, United States
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32
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Kenkel W. Birth signalling hormones and the developmental consequences of caesarean delivery. J Neuroendocrinol 2021; 33:e12912. [PMID: 33145818 PMCID: PMC10590550 DOI: 10.1111/jne.12912] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 10/05/2020] [Accepted: 10/06/2020] [Indexed: 12/12/2022]
Abstract
Rates of delivery by caesarean section (CS) are increasing around the globe and, although several epidemiological associations have already been observed between CS and health outcomes in later life, more are sure to be discovered as this practice continues to gain popularity. The components of vaginal delivery that protect offspring from the negative consequences of CS delivery in later life are currently unknown, although much attention to date has focused on differences in microbial colonisation. Here, we present the case that differing hormonal experiences at birth may also contribute to the neurodevelopmental consequences of CS delivery. Levels of each of the 'birth signalling hormones' (oxytocin, arginine vasopressin, epinephrine, norepinephrine and the glucocorticoids) are lower following CS compared to vaginal delivery, and there is substantial evidence for each that manipulations in early life results in long-term neurodevelopmental consequences. We draw from the research traditions of neuroendocrinology and developmental psychobiology to suggest that the perinatal period is a sensitive period, during which hormones achieve organisational effects. Furthermore, there is much to be learned from research on developmental programming by early-life stress that may inform research on CS, as a result of shared neuroendocrine mechanisms at work. We compare and contrast the effects of early-life stress with those of CS delivery and propose new avenues of research based on the links between the two bodies of literature. The research conducted to date suggests that the differences in hormone signalling seen in CS neonates may produce long-term neurodevelopmental consequences.
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Affiliation(s)
- William Kenkel
- Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, USA
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33
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Shaw JC, Crombie GK, Palliser HK, Hirst JJ. Impaired Oligodendrocyte Development Following Preterm Birth: Promoting GABAergic Action to Improve Outcomes. Front Pediatr 2021; 9:618052. [PMID: 33634057 PMCID: PMC7901941 DOI: 10.3389/fped.2021.618052] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 01/12/2021] [Indexed: 11/21/2022] Open
Abstract
Preterm birth is associated with poor long-term neurodevelopmental and behavioral outcomes, even in the absence of obvious brain injury at the time of birth. In particular, behavioral disorders characterized by inattention, social difficulties and anxiety are common among children and adolescents who were born moderately to late preterm (32-37 weeks' gestation). Diffuse deficits in white matter microstructure are thought to play a role in these poor outcomes with evidence suggesting that a failure of oligodendrocytes to mature and myelinate axons is responsible. However, there remains a major knowledge gap over the mechanisms by which preterm birth interrupts normal oligodendrocyte development. In utero neurodevelopment occurs in an inhibitory-dominant environment due to the action of placentally derived neurosteroids on the GABAA receptor, thus promoting GABAergic inhibitory activity and maintaining the fetal behavioral state. Following preterm birth, and the subsequent premature exposure to the ex utero environment, this action of neurosteroids on GABAA receptors is greatly reduced. Coinciding with a reduction in GABAergic inhibition, the preterm neonatal brain is also exposed to ex utero environmental insults such as periods of hypoxia and excessive glucocorticoid concentrations. Together, these insults may increase levels of the excitatory neurotransmitter glutamate in the developing brain and result in a shift in the balance of inhibitory: excitatory activity toward excitatory. This review will outline the normal development of oligodendrocytes, how it is disrupted under excitation-dominated conditions and highlight how shifting the balance back toward an inhibitory-dominated environment may improve outcomes.
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Affiliation(s)
- Julia C Shaw
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.,Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Gabrielle K Crombie
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.,Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Hannah K Palliser
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.,Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Jonathan J Hirst
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.,Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
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Orso R, Creutzberg KC, Kestering-Ferreira E, Wearick-Silva LE, Tractenberg SG, Grassi-Oliveira R. Maternal Separation Combined With Limited Bedding Increases Anxiety-Like Behavior and Alters Hypothalamic-Pituitary-Adrenal Axis Function of Male BALB/cJ Mice. Front Behav Neurosci 2020; 14:600766. [PMID: 33304248 PMCID: PMC7693708 DOI: 10.3389/fnbeh.2020.600766] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 10/15/2020] [Indexed: 11/13/2022] Open
Abstract
Early life stress (ELS) is considered a risk factor for the development of psychiatric conditions, including depression and anxiety disorder. Individuals that live in adverse environments are usually exposed to multiple stressors simultaneously, such as maternal neglect, maltreatment, and limited resources. Nevertheless, most pre-clinical ELS models are designed to explore the impact of these events separately. For this reason, this study aims to investigate the effects of a combined model of ELS on anxiety-like behavior and hypothalamic-pituitary-adrenal (HPA) axis related targets. From PND 2 to PND 15 BALB/cJ mice were exposed simultaneously to maternal separation (MS; 3 h per day) and limited bedding (LB; ELS group) or left undisturbed (CT group). Maternal behavior was recorded in intercalated days, from PND 1 to PND 9. Male offspring were tested for anxiety-like behavior from PND 53 to PND 55 in the open field test (OF), elevated plus-maze (EPM), and light/dark test (LD). After behavioral testing, animals were euthanized, and glucocorticoid receptor (Nr3c1), corticotrophin-releasing hormone (Crh), and its receptor type 1 (Crhr1) gene expression in the hypothalamus were measured. Moreover, plasma corticosterone levels were analyzed. We observed that ELS dams presented altered quality of maternal care, characterized by a decrease in arched-back nursing, and an increase in passive nursing. Stressed dams also showed an increase in the number of exits from the nest when compared to CT dams. Furthermore, ELS animals showed increased anxiety-like behavior in the OF, EPM, and LD. Regarding gene expression, we identified an increase in hypothalamus Crh levels of ELS group when compared to CT animals, while no differences in Nr3c1 and Crhr1 expression were observed. Finally, stressed animals showed decreased levels of plasma corticosterone when compared to the CT group. In conclusion, we observed an alteration in maternal behavior in ELS dams. Later in life, animals exposed to the combined model of ELS showed increased levels of anxiety-like behavior. Moreover, the central and peripheral HPA measures observed could indicate a dysregulation in HPA function provoked by ELS exposure.
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Affiliation(s)
- Rodrigo Orso
- Developmental Cognitive Neuroscience Lab (DCNL), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.,Brain Institute (InsCer), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | | | - Erika Kestering-Ferreira
- Developmental Cognitive Neuroscience Lab (DCNL), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.,Brain Institute (InsCer), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Luis Eduardo Wearick-Silva
- Developmental Cognitive Neuroscience Lab (DCNL), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.,Brain Institute (InsCer), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Saulo Gantes Tractenberg
- Developmental Cognitive Neuroscience Lab (DCNL), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.,Brain Institute (InsCer), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Rodrigo Grassi-Oliveira
- Developmental Cognitive Neuroscience Lab (DCNL), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.,Brain Institute (InsCer), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
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35
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Cella EC, Conte J, Stolte RCK, Lorenzon F, Gregorio T, Simas BB, Rafacho A, Lima FB. Gestational exposure to excessive levels of dexamethasone impairs maternal care and impacts on the offspring's survival in rats. Life Sci 2020; 264:118599. [PMID: 33127510 DOI: 10.1016/j.lfs.2020.118599] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/06/2020] [Accepted: 10/11/2020] [Indexed: 11/28/2022]
Abstract
Administration of dexamethasone (DEX) during late gestation is a model to study growth restriction in rodents, but the pup's mortality index can be high, depending on DEX dosage, and little is known about the effects of DEX on maternal care (MC). Considering that an inadequate MC can also contribute to pup's mortality in this model, we evaluated the effects of DEX on dams' behavior and its consequences on offspring survival. We also investigated whether the cross-fostering of pups from dams treated or not with DEX could improve pup's survival. Wistar rats were treated with DEX (14th to 19th day of gestation -0.2 mg/kg, B.W, in the drinking water). Nest building, MC and responses in the elevated plus-maze, forced swimming and object recognition tests were evaluated. DEX reduced gestational weight gain and impaired neonatal development, reducing pup's survival to 0% by the 3rd postnatal day. DEX-treated dams reduced the expression of typical MC and increased anxiety-like behaviors. After cross-fostering, DEX-treated mothers behaved similarly to controls, indicating that a healthy offspring is crucial to induce adequate MC. Cross-fostering increased the survival index from zero to 25% in the DEX offspring. Postnatal development of the DEX offspring was comparable to controls after cross-fostering. We concluded that exposure to DEX during late gestation causes behavioral changes that compromise the maternal emotional state, disrupting the expression of MC. Although it does not seem to be the main cause of pup's mortality, our data indicate that an adequate MC improves pup's survival in this model.
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Affiliation(s)
- Elisa C Cella
- Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus, Florianópolis, SC, Brazil
| | - Júlia Conte
- Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil
| | - Rafaela C K Stolte
- Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil
| | - Flaviano Lorenzon
- Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus, Florianópolis, SC, Brazil
| | - Tamires Gregorio
- Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus, Florianópolis, SC, Brazil
| | - Bruna B Simas
- Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil
| | - Alex Rafacho
- Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus, Florianópolis, SC, Brazil
| | - Fernanda B Lima
- Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus, Florianópolis, SC, Brazil.
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36
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Prenatal stress and epigenetics. Neurosci Biobehav Rev 2020; 117:198-210. [DOI: 10.1016/j.neubiorev.2017.05.016] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 05/15/2017] [Accepted: 05/16/2017] [Indexed: 12/22/2022]
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Hong JY, Lim J, Carvalho F, Cho JY, Vaidyanathan B, Yu S, Annicelli C, Ip WKE, Medzhitov R. Long-Term Programming of CD8 T Cell Immunity by Perinatal Exposure to Glucocorticoids. Cell 2020; 180:847-861.e15. [PMID: 32142678 DOI: 10.1016/j.cell.2020.02.018] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 11/19/2019] [Accepted: 02/07/2020] [Indexed: 12/12/2022]
Abstract
Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.
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Affiliation(s)
- Jun Young Hong
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Jaechul Lim
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Fernando Carvalho
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Jen Young Cho
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Bharat Vaidyanathan
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Shuang Yu
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Charles Annicelli
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - W K Eddie Ip
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Ruslan Medzhitov
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
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Peixoto MRLV, Karrow NA, Newman A, Widowski TM. Effects of Maternal Stress on Measures of Anxiety and Fearfulness in Different Strains of Laying Hens. Front Vet Sci 2020; 7:128. [PMID: 32292791 PMCID: PMC7118700 DOI: 10.3389/fvets.2020.00128] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 02/20/2020] [Indexed: 01/21/2023] Open
Abstract
Maternal stress can affect the offspring of birds, possibly due to hormone deposition in the egg. Additionally, phenotypic diversity resulting from domestication and selection for productivity has created a variety of poultry lines that may cope with stress differently. In this study, we investigated the effects of maternal stress on the behavior of different strains of laying hens and the role of corticosterone as its mediator. For this, fertilized eggs of five genetic lines-two brown (Brown 1 and 2), two white (White 1 and 2), and one pure line White Leghorn-were reared identically as four flocks of 27 birds (24F: 3M) per strain. Each strain was equally separated into two groups: Maternal Stress ("MS"), where hens were subjected to a series of daily acute psychological stressors for 8 days before egg collection, and "Control," which received routine husbandry. Fertile eggs from both treatments were collected at three different ages forming different offspring groups that were treated as replicates; additional eggs from Control were injected either with corticosterone diluted in a vehicle solution ("CORT") or just "Vehicle." Eggs from each replicate were incubated and hatched, and offspring (N = 1,919) were brooded under identical conditions. To measure the effects of maternal stress on anxiety and fear-like behavior, offspring were subjected to a social isolation test (SI) between 5 and 10 days of age and a tonic immobility test (TI) at 9 weeks of age. Compared to Control, MS decreased the number of distress vocalizations emitted by White 2 in SI. No effects of MS were observed in TI, and no effects of CORT were observed in any tests. Overall, brown lines vocalized more in SI and remained in TI for a longer duration than white strains, suggesting genetic differences in fear behavior. Females vocalized more than males in TI and showed a trend toward significance for the same trait in SI. Overall, results suggest that the effects of maternal stress on fearfulness are not directly mediated by corticosterone. Moreover, it highlights behavioral differences across various strains of laying hens, suggesting that fear responses are highly dependent on genotype.
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Affiliation(s)
| | - Niel A. Karrow
- Department of Animal Biosciences, University of Guelph, Guelph, ON, Canada
| | - Amy Newman
- Department of Integrative Biology, University of Guelph, Guelph, ON, Canada
| | - Tina M. Widowski
- Department of Animal Biosciences, University of Guelph, Guelph, ON, Canada
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39
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Hrabalkova L, Takahashi T, Kemp MW, Stock SJ. Antenatal Corticosteroids for Fetal Lung Maturity - Too Much of a Good Thing? Curr Pharm Des 2020; 25:593-600. [PMID: 30914016 DOI: 10.2174/1381612825666190326143814] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 03/22/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Between 5-15% of babies are born prematurely worldwide, with preterm birth defined as delivery before 37 completed weeks of pregnancy (term is at 40 weeks of gestation). Women at risk of preterm birth receive antenatal corticosteroids as part of standard care to accelerate fetal lung maturation and thus improve neonatal outcomes in the event of delivery. As a consequence of this treatment, the entire fetal organ system is exposed to the administered corticosteroids. The implications of this exposure, particularly the long-term impacts on offspring health, are poorly understood. AIMS This review will consider the origins of antenatal corticosteroid treatment and variations in current clinical practices surrounding the treatment. The limitations in the evidence base supporting the use of antenatal corticosteroids and the evidence of potential harm to offspring are also summarised. RESULTS Little has been done to optimise the dose and formulation of antenatal corticosteroid treatment since the first clinical trial in 1972. International guidelines for the use of the treatment lack clarity regarding the recommended type of corticosteroid and the gestational window of treatment administration. Furthermore, clinical trials cited in the most recent Cochrane Review have limitations which should be taken into account when considering the use of antenatal corticosteroids in clinical practice. Lastly, there is limited evidence regarding the long-term effects on the different fetal organ systems exposed in utero, particularly when the timing of corticosteroid administration is sub-optimal. CONCLUSION Further investigations are urgently needed to determine the most safe and effective treatment regimen for antenatal corticosteroids, particularly regarding the type of corticosteroid and optimal gestational window of administration. A clear consensus on the use of this common treatment could maximise the benefits and minimise potential harms to offspring.
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Affiliation(s)
- Lenka Hrabalkova
- Tommy's Centre for Maternal and Fetal Health at the MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom
| | | | - Matthew W Kemp
- Tohoku University Hospital, Sendai, Miyagi, Japan.,Division of Obstetrics and Gynaecology, University of Western Australia, Perth, Australia
| | - Sarah J Stock
- Tommy's Centre for Maternal and Fetal Health at the MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.,Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
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40
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Castelli V, Lavanco G, Brancato A, Plescia F. Targeting the Stress System During Gestation: Is Early Handling a Protective Strategy for the Offspring? Front Behav Neurosci 2020; 14:9. [PMID: 32082129 PMCID: PMC7006220 DOI: 10.3389/fnbeh.2020.00009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 01/15/2020] [Indexed: 12/28/2022] Open
Abstract
The perinatal window is a critical developmental time when abnormal gestational stimuli may alter the development of the stress system that, in turn, influences behavioral and physiological responses in the newborns. Individual differences in stress reactivity are also determined by variations in maternal care, resulting from environmental manipulations. Despite glucocorticoids are the primary programming factor for the offspring's stress response, therapeutic corticosteroids are commonly used during late gestation to prevent preterm negative outcomes, exposing the offspring to potentially aberrant stress reactivity later in life. Thus, in this study, we investigated the consequences of one daily s.c. injection of corticosterone (25 mg/kg), from gestational day (GD) 14-16, and its interaction with offspring early handling, consisting in a brief 15-min maternal separation until weaning, on: (i) maternal behavior; and (ii) behavioral reactivity, emotional state and depressive-like behavior in the adolescent offspring. Corticosterone plasma levels, under non-shock- and shock-induced conditions, were also assessed. Our results show that gestational exposure to corticosterone was associated with diminished maternal care, impaired behavioral reactivity, increased emotional state and depressive-like behavior in the offspring, associated with an aberrant corticosterone response. The early handling procedure, which resulted in increased maternal care, was able to counteract the detrimental effects induced by gestational corticosterone exposure both in the behavioral- and neurochemical parameters examined. These findings highlight the potentially detrimental consequences of targeting the stress system during pregnancy as a vulnerability factor for the occurrence of emotional and affective distress in the adolescent offspring. Maternal extra-care proves to be a protective strategy that confers resiliency and restores homeostasis.
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Affiliation(s)
- Valentina Castelli
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Gianluca Lavanco
- INSERM U1215, Neuro Centre Magendie, Bordeaux, France.,University of Bordeaux, Bordeaux, France.,Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy
| | - Anna Brancato
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy
| | - Fulvio Plescia
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy
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41
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Shaw JC, Crombie GK, Zakar T, Palliser HK, Hirst JJ. Perinatal compromise contributes to programming of GABAergic and glutamatergic systems leading to long-term effects on offspring behaviour. J Neuroendocrinol 2020; 32:e12814. [PMID: 31758712 DOI: 10.1111/jne.12814] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 10/30/2019] [Accepted: 11/20/2019] [Indexed: 01/01/2023]
Abstract
Extensive evidence now shows that adversity during the perinatal period is a significant risk factor for the development of neurodevelopmental disorders long after the causative event. Despite stemming from a variety of causes, perinatal compromise appears to have similar effects on the developing brain, thereby resulting in behavioural disorders of a similar nature. These behavioural disorders occur in a sex-dependent manner, with males affected more by externalising behaviours such as attention deficit hyperactivity disorder (ADHD) and females by internalising behaviours such as anxiety. Regardless of the causative event or the sex of the offspring, these disorders may begin in childhood or adolescence but extend into adulthood. A mechanism by which adverse events in the perinatal period impact later in life behaviour has been shown to be the changing epigenetic landscape. Methylation of the GAD1/GAD67 gene, which encodes the key glutamate-to-GABA-synthesising enzyme glutamate decarboxylase 1, resulting in increased levels of glutamate, is one epigenetic mechanism that may account for a tendency towards excitation in disorders such as ADHD. Exposure of the fetus or the neonate to high levels of cortisol may be the mediator between perinatal compromise and poor behavioural outcomes because evidence suggests that increased glucocorticoid exposure triggers widespread changes in the epigenetic landscape. This review summarises the current evidence and recent literature about the impact of various perinatal insults on the epigenome and the common mechanisms that may explain the similarity of behavioural outcomes occurring following diverse perinatal compromise.
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Affiliation(s)
- Julia C Shaw
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
- Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Gabrielle K Crombie
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
- Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Tamas Zakar
- Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
- School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
| | - Hannah K Palliser
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
- Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Jonathan J Hirst
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
- Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
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Wolford E, Lahti-Pulkkinen M, Girchenko P, Lipsanen J, Tuovinen S, Lahti J, Heinonen K, Hämäläinen E, Kajantie E, Pesonen AK, Villa PM, Laivuori H, Reynolds RM, Räikkönen K. Associations of antenatal glucocorticoid exposure with mental health in children. Psychol Med 2020; 50:247-257. [PMID: 30688183 DOI: 10.1017/s0033291718004129] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Synthetic glucocorticoids, to enhance fetal maturation, are a standard treatment when preterm birth before 34 gestational weeks is imminent. While morbidity- and mortality-related benefits may outweigh potential neurodevelopmental harms in children born preterm (<37 gestational weeks), this may not hold true when pregnancy continues to term (⩾37 gestational weeks). We studied the association of antenatal betamethasone exposure on child mental health in preterm and term children. METHODS We included 4708 women and their children, born 2006-2010, from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction Study with information on both antenatal betamethasone treatment and child mental and behavioral disorders from the Finnish Hospital Discharge Register from the child's birth to 31 December 2016. Additional follow-up data on mother-reported psychiatric problems and developmental milestones were available for 2640 children at 3.5 (s.d. = 0.07) years-of-age. RESULTS Of the children, 187 were born preterm (61 betamethasone-exposed) and 4521 at term (56 betamethasone-exposed). The prevalence of any mental and behavioral, psychological development, emotional and behavioral, and comorbid disorders was higher in the betamethasone-exposed, compared to non-exposed children [odds ratio 2.76 (95% confidence interval 1.76-4.32), 3.61 (2.19-5.95), 3.29 (1.86-5.82), and 6.04 (3.25-11.27), respectively]. Levels of psychiatric problems and prevalence of failure to meet the age-appropriate development in personal-social skills were also higher in mother-reports of betamethasone-exposed children. These associations did not vary significantly between preterm and term children. CONCLUSIONS Antenatal betamethasone exposure may be associated with mental health problems in children born preterm and in those who end up being born at term.
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Affiliation(s)
- Elina Wolford
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Marius Lahti-Pulkkinen
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Polina Girchenko
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Jari Lipsanen
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Soile Tuovinen
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Jari Lahti
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland
- Folkhälsan Research Centre, Helsinki, Finland
| | - Kati Heinonen
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Esa Hämäläinen
- Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland
| | - Eero Kajantie
- National Institute for Health and Welfare, Helsinki, Finland
- Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Anu-Katriina Pesonen
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Pia M Villa
- Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Hannele Laivuori
- Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland
- Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
| | - Rebecca M Reynolds
- University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Katri Räikkönen
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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Ellman LM, Murphy SK, Maxwell SD, Calvo EM, Cooper T, Schaefer CA, Bresnahan MA, Susser ES, Brown AS. Maternal cortisol during pregnancy and offspring schizophrenia: Influence of fetal sex and timing of exposure. Schizophr Res 2019; 213:15-22. [PMID: 31345704 PMCID: PMC7074891 DOI: 10.1016/j.schres.2019.07.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 06/28/2019] [Accepted: 07/02/2019] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Maternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for an intermediate phenotype-decreased fetal growth-previously linked to prenatal cortisol and schizophrenia. Timing of exposure and fetal sex also were examined given previous findings. METHODS Participants were 64 cases diagnosed with schizophrenia spectrum disorders (SSD) and 117 controls from a prospective birth cohort study. Maternal cortisol was determined from stored sera from each trimester and psychiatric diagnoses were assessed from offspring using semi-structured interviews and medical records review. RESULTS Maternal cortisol during pregnancy was not associated with risk for offspring schizophrenia. There was a significant interaction between 3rd trimester cortisol and case status on fetal growth. Specifically, cases exposed to higher 3rd trimester maternal cortisol had significantly decreased fetal growth compared to controls. In addition, these findings were restricted to male offspring. CONCLUSIONS Our results indicate that higher prenatal cortisol is associated with an intermediate phenotype linked to schizophrenia, fetal growth, but only among male offspring who developed schizophrenia. Findings were consistent with evidence that schizophrenia genes may disrupt placental functioning specifically for male fetuses, as well as findings that males are more vulnerable to maternal cortisol during pregnancy. Finally, results suggest that examining fetal sex and intermediate phenotypes may be important in understanding the mechanisms involved in prenatal contributors to schizophrenia.
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Affiliation(s)
- Lauren M Ellman
- Department of Psychology, Temple University, Weiss Hall, 1701 N. 13(th) Street, Philadelphia, PA 19106, United States of America.
| | - Shannon K Murphy
- Department of Psychology, Temple University, Weiss Hall, 1701 N. 13(th) Street, Philadelphia, PA 19106, United States of America.
| | - Seth D Maxwell
- Department of Psychology, Temple University, Weiss Hall, 1701 N. 13(th) Street, Philadelphia, PA 19106, United States of America.
| | - Evan M Calvo
- Department of Psychology, Temple University, Weiss Hall, 1701 N. 13(th) Street, Philadelphia, PA 19106, United States of America.
| | - Thomas Cooper
- Analytic Psychopharmacology, Nathan S. Kline Institute, 140 Old Orangeburg Road Orangeburg, NY 10962, United States of America; New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States of America; Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, United States of America.
| | - Catherine A Schaefer
- Division of Research, Kaiser Permanente, 2000 Broadway, Oakland, CA 94612, United States of America.
| | - Michaeline A Bresnahan
- Department of Epidemiology, Columbia University Mailman School of Public Health, 722 West 168(th) Street, New York, NY 10032, United States of America; New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States of America.
| | - Ezra S Susser
- Department of Epidemiology, Columbia University Mailman School of Public Health, 722 West 168(th) Street, New York, NY 10032, United States of America; New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States of America.
| | - Alan S Brown
- Department of Epidemiology, Columbia University Mailman School of Public Health, 722 West 168(th) Street, New York, NY 10032, United States of America; New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States of America; Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, United States of America.
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The effects of prenatal dexamethasone exposure and fructose challenge on pituitary-adrenocortical activity and anxiety-like behavior in female offspring. Tissue Cell 2019; 62:101309. [PMID: 32433017 DOI: 10.1016/j.tice.2019.101309] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/14/2019] [Accepted: 10/15/2019] [Indexed: 11/20/2022]
Abstract
Prenatal glucocorticoid overexposure could largely influence pituitary-adrenal activity and anxiety-like behavior in offspring. Our aim was to study the possible potentiating effect of moderate dose of fructose - common ingredient of today's diet - on prenatal glucocorticoid treatment-induced hypothalamo-pituitary-adrenal (HPA) axis changes. Pregnant female rats were treated with multiple dexamethasone (Dx) doses (3 x 0.5 mg/kg/b.m. Dx; 16th-18th gestational day). Half of female offspring from control and Dx treated dams were supplemented with 10% fructose solution, from weaning till adulthood. Immunohistochemistry, unbiased stereological evaluation and hormonal analysis are used to provide the morpho-functional state of pituitary and adrenal gland. Anxiety-like behavior was assessed using the light/dark box test and the elevated plus maze test. Prenatally Dx exposed females, with or without fructose consumption, had markedly reduced adrenocortical volume (p < 0.05) comparing to controls. Increased basal plasma ACTH level in these females (p < 0.05) maintained corticosterone concentration at control level produced by smaller adrenal glands. In parallel, anxiety-like behavior was shown by both tests used. In conclusion, prenatal Dx exposure cause negative psychophysiological outcome reflected in increased HPA axis activity and anxiety behavior in female offspring, while moderately increased fructose consumption failed to evoke any alteration or to potentiate effects of prenatal Dx exposure.
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Fetal programming of adrenal PNMT and hypertension by glucocorticoids in WKY rats is dose and sex-dependent. PLoS One 2019; 14:e0221719. [PMID: 31483805 PMCID: PMC6726223 DOI: 10.1371/journal.pone.0221719] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 08/13/2019] [Indexed: 12/12/2022] Open
Abstract
Biochemical changes in utero may alter normal fetal development, resulting in disease later in life, a phenomenon known as fetal programming. Recent epidemiological studies link fetal programming to negative health outcomes, such as low birth weight and hypertension in adulthood. Here, we used a WKY rat model and studied the molecular changes triggered by prenatal glucocorticoid (GC) exposure on the development of hypertension, and on the regulation of phenylethanolamine N-methyl transferase (PNMT), the enzyme responsible for biosynthesis of epinephrine, and a candidate gene linked to hypertension. Clinically, high doses of the synthetic GC dexamethasone (DEX) are used to treat infant respiratory distress syndrome. Elevated maternal GCs have been correlated with fetal programming of hypertension. The aim of this study was to determine if lower doses of DEX would not lead to detrimental fetal programming effects such as hypertension. Our data suggests that prenatal stress programs for increased expression of PNMT and altered regulation of PNMT in males and females. Importantly, we identified that DEX mediated programming was more apparent in the male rats, and the lower dose 10μg/kg/day of DEX did not lead to changes in blood pressure (BP) in female rats suggesting that this dose is below the threshold for programming of hypertension. Furthermore, sex-specific differences were observed in regards to programming mechanisms that may account for hypertension in males.
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Wang Y, Zhang H, Jiang JM, Zheng D, Tan HS, Tang LM, Xu HX. Multiorgan toxicity induced by EtOH extract of Fructus Psoraleae in Wistar rats. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 58:152874. [PMID: 30889421 DOI: 10.1016/j.phymed.2019.152874] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2018] [Revised: 02/10/2019] [Accepted: 02/23/2019] [Indexed: 06/09/2023]
Abstract
BACKGROUND The fruits of Psoralea corylifolia L. (Fructus Psoraleae, FP) has a long history and a wide range of applications in the treatment of osteoporosis and leukoderma. Although it is well known that FP could cause hepatotoxicity and reproductive toxicity, less is known about its potential toxicity on multiple organs. PURPOSE This study aims to determine the multiorgan toxicity of EtOH extract of FP (EEFP) and to investigate the underlying mechanisms through a systematic evaluation in Wistar rats. STUDY DESIGN AND METHODS Wistar rats were orally administered with the EEFP at doses of 1.5, 1.0 and 0.5 g/kg for 28 days. Histopathologic and clinicopathologic analyses were performed, and the hormone levels in serum and the mRNA levels of enzymes related to the production of steroid hormones in adrenal glands were detected. The area of each band of adrenal glands and the steroid levels in the adrenal glands were also measured. RESULTS After the treatment, both the histopathologic and clinicopathologic examination showed that EEFP caused liver, prostate, seminal vesicle and adrenal gland damage. Among the enzymes involved in the regulation of adrenal steroid hormone production, NET, VMAT2, and CYP11B1 were upregulated, while CYP17A1 was downregulated. Among the adrenal steroid hormones, COR and NE were upregulated, while levels of DHT and serum ACRH and CRH decreased. CONCLUSION Our results indicated that adrenal gland, prostate, and seminal vesicles could also be the target organs of FP-induced toxicity. Abnormal enzyme and hormone production related to the hypothalamic pituitary adrenal (HPA) axis caused by the EEFP may be the potential toxic mechanism for changes in the adrenal gland and secondary sex organs of male rats.
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Affiliation(s)
- Yu Wang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China
| | - Hong Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China
| | - Jia-Ming Jiang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China
| | - Dan Zheng
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China
| | - Hong-Sheng Tan
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China
| | - Li-Ming Tang
- Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, PR China.
| | - Hong-Xi Xu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China.
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Schuetze P, Zhao J, Eiden RD, Shisler S, Huestis MA. Prenatal exposure to tobacco and marijuana and child autonomic regulation and reactivity: An analysis of indirect pathways via maternal psychopathology and parenting. Dev Psychobiol 2019; 61:1022-1034. [PMID: 30868568 DOI: 10.1002/dev.21844] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 01/16/2019] [Accepted: 01/30/2019] [Indexed: 11/08/2022]
Abstract
We examined a conceptual model for the associations of prenatal exposure to tobacco (PTE) and marijuana with child reactivity/regulation at 16 months of age. We hypothesized that PTE would be associated with autonomic reactivity and regulation that these associations would be indirect via maternal anger/hostility, depression/stress, or harsh parenting assessed at 2 months and that these effects would be most pronounced among children exposed to both tobacco and marijuana (PTME). Participants were 247 dyads (81 PTE, 97 PTME, and 69 nonexposed) who were followed up at 2 (N = 247) and 16 months (N = 238) of child age. Results from model testing indicated an indirect association between PTME and autonomic functioning during the second year of life, which was mediated by harsh parenting during caregiver-infant interactions. This study fills an important gap in the literature on PTE, PTME, and autonomic regulation during the toddler years, highlighting the role of maternal parenting as important intervening variables.
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Affiliation(s)
- Pamela Schuetze
- Department of Psychology, State University of New York Buffalo State, Buffalo, New York.,Clinical and Research Institute on Addictions, University at Buffalo, Buffalo, New York
| | - Junru Zhao
- Clinical and Research Institute on Addictions, University at Buffalo, Buffalo, New York
| | - Rina D Eiden
- Department of Psychology, University at Buffalo, Buffalo, New York
| | - Shannon Shisler
- Department of Psychology, University at Buffalo, Buffalo, New York
| | - Marilyn A Huestis
- The Lambert Center for the Study of Medicinal Cannabis and Hemp, Thomas Jefferson, Philadelphia, PA
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48
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Liu CH, Doan SN. Innovations in biological assessments of chronic stress through hair and nail cortisol: Conceptual, developmental, and methodological issues. Dev Psychobiol 2019; 61:465-476. [PMID: 30740655 DOI: 10.1002/dev.21830] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 11/12/2018] [Accepted: 12/10/2018] [Indexed: 12/20/2022]
Abstract
Much of the existing research on biological mechanisms underlying the stress experience has focused largely on moment-to-moment stress, rather than on chronic stress, an arguably more powerful predictor of long-term outcomes. Recent methodological innovations have paved the way for new lines of research on chronic stress, with promising implications for developmental researchers and for those who study health and adversity. In particular, there are increasing studies that have focused on chronic stress assessments by relying on cortisol derived from hair and nails as a biomarker for chronic stress. In this paper, we provide an overview of their use, describe how hair and nail cortisol ought to be conceptualized differently across the lifespan, how developmental factors may impact its interpretation, and the circumstances under which its use may be more methodologically sensible. The purpose of this review is to provoke further discussion and encourage careful research designs that utilize hair and nail cortisol for understanding the effects of chronic stress exposure from the early developmental period, across adverse contexts, and in association with psychological and physical health outcomes.
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Affiliation(s)
- Cindy H Liu
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Stacey N Doan
- Department of Psychology, Claremont McKenna College, Claremont, CA
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Huang K, Yan S, Wu X, Zhu P, Tao F. Elective caesarean section on maternal request prior to 39 gestational weeks and childhood psychopathology: a birth cohort study in China. BMC Psychiatry 2019; 19:22. [PMID: 30642307 PMCID: PMC6332907 DOI: 10.1186/s12888-019-2012-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 01/04/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND The recommendation of non-indicated caesarean section (CS) after 39 gestational weeks has been announced based on evidence of maternal and infant physiological effects. The potential psychological risks have not been acknowledged. This study aims to investigate emotional and behavioral problems in pre-school children born with elective CS (ECS) on maternal request prior to 39 weeks. METHODS Pregnant women within 12 gestational weeks between November 2008 and October 2010 were invited to participate in the China-Anhui Birth Cohort Study (C-ABCS). They were asked to complete a self-administered questionnaire respectively in 1st and 3rd trimester of pregnancy to collect basic maternal characteristics. Pregnant complications and delivery modes were abstracted from medical notes. Their singleton live births were followed up at preschool age. Strengths and Difficulties Questionnaires (SDQ) were completed by parents to assess children's emotional and behavioral problems. A total of 3319 mother-child pairs were put into the final analysis. Descriptive analysis and binary logistic regression analysis were used to assess the impact of delivery modes on abnormalities in SDQ dimensions at various gestational ages. RESULTS The prevalence of ECS on maternal request prior to 39 weeks, at 39-40 weeks, and after 41 weeks was 16.6, 23.7 and 15.9%, respectively. Compared with those born vaginally, children born with ECS on maternal request were more likely to have total difficult problems (RR 1.519, 95% confidence interval 1.077 to 2.142). ECS on maternal request was the independent predictor of emotional problems (3.479, 1.676 to 7.222) and total difficult problems (2.172, 1.175 to 4.016) in children born prior to 39 gestational weeks. CONCLUSION Children delivered by ECS on maternal request have an increased risk to have emotional and behavioral problems prior to 39 gestational weeks at preschool age. The potential psychological implication prior to 39 weeks has been added to the roster of impacts of ECS on maternal request. Further research is needed to probe the potential biological mechanisms.
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Affiliation(s)
- Kun Huang
- School of Public Health, Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui Province China
| | - Shuangqin Yan
- Ma’anshan Maternal and Child Health Center, No 72 Jiashan Road, Ma’anshan, Anhui Province China
| | - Xiaoyan Wu
- School of Public Health, Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui Province China
| | - Peng Zhu
- School of Public Health, Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui Province China
| | - Fangbiao Tao
- School of Public Health, Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui Province China
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Huang K, Hu Y, Sun Y, Yu Z, Liu W, Zhu P, Tao F. Elective caesarean delivery and offspring’s cognitive impairment: Implications of methylation alteration in hippocampus glucocorticoid signaling genes. Brain Res Bull 2019; 144:108-121. [DOI: 10.1016/j.brainresbull.2018.11.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 11/09/2018] [Accepted: 11/21/2018] [Indexed: 12/16/2022]
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