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Dufault RJ. Biomarkers for tracking metabolic changes pre-post nutritional epigenetics diet/intervention to prevent autism and attention deficit/hyperactivity disorders in children. World J Exp Med 2025; 15:101555. [DOI: 10.5493/wjem.v15.i2.101555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/20/2025] [Accepted: 02/06/2025] [Indexed: 04/16/2025] Open
Abstract
The prevalence of autism and attention deficit/hyperactivity disorders is increasing worldwide. Recent studies suggest the excessive intake of ultra-processed food plays a role in the inheritance of these disorders via heavy metal exposures and nutritional deficits that impact the expression of genes. In the case of the metallothionein (MT) gene, biomarker studies show dietary zinc (Zn) deficits impact MT protein levels in children with autism and are associated with the bioaccumulation of lead and/or mercury in children exhibiting autism/attention deficit/hyperactivity disorders symptomology. The impact of dietary changes on lead and mercury exposures and MT gene behavior could be determined using a randomized test and control group design. Pregnant women serving in the test-group would participate in a nutritional epigenetics education intervention/course designed to reduce ultra-processed food intake and heavy metal levels in blood while increasing whole food intake and MT and Zn levels. Changes in maternal diet would be measured using data derived from an online diet survey administered to the test and control groups pre-post intervention. Changes in maternal lead, mercury, Zn, and MT levels would be measured via blood sample analyses prior to the intervention and after childbirth via cord blood analyses to determine infant risk factors.
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Affiliation(s)
- Renee J Dufault
- College of Graduate Health Studies, A.T. Still University, Kirksville, MO 63501, United States
- Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
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Vasquez LS, Stack S, Taylor WW, Dias BG. Intergenerational Effects of Stress - A Focus on Learning and Memory. Curr Top Behav Neurosci 2025. [PMID: 40119217 DOI: 10.1007/7854_2025_578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2025]
Abstract
Stress is a ubiquitous facet of life. Ranging in form (e.g., psychosocial, physical, nutritional, economic) and longevity (e.g., acute, chronic), stressors affect the biology of those directly in their line of attack. As is becoming increasingly appreciated, the pernicious effects of stress echo across generations (Dias et al. 2015; Yehuda and Lehrner 2018; Jawaid et al. 2021; Dion et al. 2022; Zhou and Ryan 2023; Dias 2024). With a focus on learning and memory, this chapter addresses how stressors derail learning and memory in the generation directly exposed to them andin future generations. To do so, with a specific emphasis on associative fear conditioning in humans and rodents, we touch upon the relevance of extinction training in the aftermath of such conditioning and the recall of such extinction training as windows into normative and disrupted learning. Next, we briefly discuss underlying neuroanatomical substrates mediating these processes. We then draw attention to influences of postnatal, in utero, and pre-conceptional stress on learning and memory across generations. Finally, we briefly outline biological factors that underlie how learning and memory is derailed by these stressors.
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Affiliation(s)
- L S Vasquez
- Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA
- Developmental Neuroscience and Neurogenetics Program, The Saban Research Institute, Los Angeles, CA, USA
| | - S Stack
- Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA
- Developmental Neuroscience and Neurogenetics Program, The Saban Research Institute, Los Angeles, CA, USA
| | - W W Taylor
- Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA
- Developmental Neuroscience and Neurogenetics Program, The Saban Research Institute, Los Angeles, CA, USA
| | - B G Dias
- Developmental Neuroscience and Neurogenetics Program, The Saban Research Institute, Los Angeles, CA, USA.
- Division of Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, USA.
- Department of Pediatrics, Keck School of Medicine of USC, Los Angeles, CA, USA.
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Charney E, Darity W, Hubbard L. How epigenetic inheritance fails to explain the Black-White health gap. Soc Sci Med 2025; 366:117697. [PMID: 39827685 DOI: 10.1016/j.socscimed.2025.117697] [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: 07/02/2024] [Revised: 12/19/2024] [Accepted: 01/10/2025] [Indexed: 01/22/2025]
Abstract
Slavery, legal segregation, and ongoing discrimination have exacted an unfathomable toll on the black population in the United States, particularly with respect to the impact on health outcomes. In recent years, various researchers and activists have suggested that racial disparities in the modern era can be attributed directly to the trauma of slavery, postulating that these unspeakable traumas led to epigenetic changes in slaves-changes that have since been passed down to subsequent generations. Investigating those claims in this paper, we comprise a review of previous literature that considers the potential for transgenerational epigenetic transmission of trauma in humans. However, we find that there is little evidence to indicate the presence of transgenerational epigenetic transmission of trauma in humans. We find no prior evidence that supports (or is relevant to) the notion that the black-white health gap stems from the inherited trauma of slavery. We conclude that, given the ongoing traumas black Americans are exposed to in modern America, it is much more likely that present-day racial health disparities are due to more direct and current mechanisms than transgenerational transmission of slavery-era trauma.
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Affiliation(s)
| | - William Darity
- Samuel DuBois Cook Center on Social Equity at Duke University, Durham, NC, USA.
| | - Lucas Hubbard
- Samuel DuBois Cook Center on Social Equity at Duke University, Durham, NC, USA.
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Poblacion A, Ettinger de Cuba S, Black MM, Weijer I, Giudice C, Esteves G, Fabian P, Zanobetti A, Cutts DB, Lê-Scherban F, Sandel M, Ochoa ER, Frank DA. Food Insecurity and Weight Faltering: US Multisite Analysis of Young Children's Weight Trajectory. J Acad Nutr Diet 2024:S2212-2672(24)01005-0. [PMID: 39644920 DOI: 10.1016/j.jand.2024.12.004] [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: 12/11/2023] [Revised: 11/25/2024] [Accepted: 12/03/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND Food insecurity is associated with poor health and development among young children, with inconsistent findings related to longitudinal growth. OBJECTIVE The aim of this study was to investigate associations between household and child food insecurity and young children's weight trajectory during ages 0 to 2 years. DESIGN Longitudinal survey data were analyzed for years 2009 to 2018. PARTICIPANTS/SETTING Racially diverse mothers of 814 children ≤24 months interviewed twice (interval >6 months, mean 11 months) in emergency departments of 4 US cities. Children were included if born at term, with birth weight within 2500 to 4500 g, and weight-for-age z score within ±2 SD at first interview. MAIN OUTCOME MEASURES Weight-for-age z score difference between 2 visits was defined as "expected weight gain" (within ±1.34 SD), "slow weight gain" (< -1.34 SD), or "rapid weight gain" (> +1.34 SD). STATISTICAL ANALYSES PERFORMED Multinomial logistic regression was conducted to examine adjusted associations between household or child food insecurity and weight-for-age z score differences. RESULTS Of 814 children, 83.5% had expected weight gain, 7% had slow weight gain, and 9.5% had rapid weight gain, with mean ± SD of 11 ± 4 months between visits. Child food insecurity, but not household food insecurity, was associated with slow weight gain (adjusted relative risk ratio 2.44; 95% CI 1.16 to 5.13 and adjusted relative risk ratio 1.30; 95% CI 0.69 to 2.51, respectively). Neither exposure was associated with rapid weight gain. CONCLUSIONS The association between child food insecurity and slow weight gain during the first 2 years of life raises clinical concern. Tracking child food insecurity in addition to household food insecurity can be an effective strategy to prevent weight faltering and to support optimal child growth.
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Affiliation(s)
- Ana Poblacion
- Children's HealthWatch, Boston Medical Center, Boston, Massachusetts.
| | - Stephanie Ettinger de Cuba
- Children's HealthWatch, Boston Medical Center, Boston, Massachusetts; Department of Health Law, Policy & Management, School of Public Health, Boston University, Boston, Massachusetts
| | - Maureen M Black
- Division of Growth & Nutrition, Department of Pediatrics, School of Medicine, University of Maryland, Baltimore, Maryland; RTI International, Research Triangle Park, North Carolina
| | - Ian Weijer
- Boston Children's Hospital, Boston, Massachusetts
| | | | - Georgiana Esteves
- School of Public Health, University of Nevada Las Vegas, Las Vegas, Nevada
| | - Patricia Fabian
- Department of Environmental Health, School of Public Health, Boston University, Boston, Massachusetts
| | - Antonella Zanobetti
- Department of Environmental Health, TH Chan School of Public Health, Harvard University, Boston, Massachusetts
| | - Diana B Cutts
- Department of Pediatrics, Hennepin County Medical Center, Minneapolis, Minnesota
| | - Félice Lê-Scherban
- Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania
| | - Megan Sandel
- Department of Pediatrics, School of Medicine, Boston University, Boston, Massachusetts
| | - Eduardo R Ochoa
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Deborah A Frank
- Department of Pediatrics, School of Medicine, Boston University, Boston, Massachusetts
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Richards-Steed R, Wan N, Bakian A, Medina RM, Brewer SC, Smith KR, VanDerslice JA. Observational methods for human studies of transgenerational effects. Epigenetics 2024; 19:2366065. [PMID: 38870389 PMCID: PMC11178273 DOI: 10.1080/15592294.2024.2366065] [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: 02/02/2024] [Accepted: 06/05/2024] [Indexed: 06/15/2024] Open
Abstract
There are substantial challenges in studying human transgenerational epigenetic outcomes resulting from environmental conditions. The task requires specialized methods and tools that incorporate specific knowledge of multigenerational relationship combinations of probands and their ancestors, phenotype data for individuals, environmental information of ancestors and their descendants, which can span historical to present datasets, and informative environmental data that chronologically aligns with ancestors and descendants over space and time. As a result, there are few epidemiologic studies of potential transgenerational effects in human populations, thus limiting the knowledge of ancestral environmental conditions and the potential impacts we face with modern human health outcomes. In an effort to overcome some of the challenges in studying human transgenerational effects, we present two transgenerational study designs: transgenerational space-time cluster detection and transgenerational case-control study design. Like other epidemiological methods, these methods determine whether there are statistical associations between phenotypic outcomes (e.g., adverse health outcomes) among probands and the shared environments and environmental factors facing their ancestors. When the ancestor is a paternal grandparent, a statistically significant association provides some evidence that a transgenerational inheritable factor may be involved. Such results may generate useful hypotheses that can be explored using epigenomic data to establish conclusive evidence of transgenerational heritable effects. Both methods are proband-centric: They are designed around the phenotype of interest in the proband generation for case selection and family pedigree creation. In the examples provided, we incorporate at least three generations of paternal lineage in both methods to observe a potential transgenerational effect.
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Affiliation(s)
| | - Neng Wan
- Geography, University of Utah Department of Geography, Salt Lake City, UT, USA
| | - Amanda Bakian
- Psychiatry, University of Utah Health, Salt Lake City, UT, USA
| | - Richard M. Medina
- Geography, University of Utah Department of Geography, Salt Lake City, UT, USA
| | - Simon C. Brewer
- Geography, University of Utah Department of Geography, Salt Lake City, UT, USA
| | - Ken R. Smith
- Child and Consumer Studies, University of Utah Health, Salt Lake City, UT, USA
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Hippman C, Nitschke AS, Hanley GE. Paternal medication dispensation around conception: A call to answer many unanswered questions. Paediatr Perinat Epidemiol 2024; 38:467-469. [PMID: 39198019 DOI: 10.1111/ppe.13111] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 07/22/2024] [Accepted: 07/26/2024] [Indexed: 09/01/2024]
Affiliation(s)
- Catriona Hippman
- Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Amanda S Nitschke
- Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Gillian E Hanley
- Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada
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De Jonge CJ, Barratt CLR, Aitken RJ, Anderson RA, Baker P, Chan DYL, Connolly MP, Eisenberg ML, Garrido N, Jørgensen N, Kimmins S, Krausz C, McLachlan RI, Niederberger C, O’Bryan MK, Pacey A, Priskorn L, Rautakallio-Hokkanen S, Serour G, Veltman JA, Vogel DL, Vazquez-Levin MH. Current global status of male reproductive health. Hum Reprod Open 2024; 2024:hoae017. [PMID: 38699533 PMCID: PMC11065475 DOI: 10.1093/hropen/hoae017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 02/22/2024] [Indexed: 05/05/2024] Open
Abstract
BACKGROUND The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline in sperm counts, has intensified concerns about the status of MRH. Consequently, there is a pressing requirement for a strategic, systematic approach to identifying critical questions, collecting pertinent information, and utilizing these data to develop evidence-based strategies. The methods for addressing these questions and the pathways toward their answers will inevitably vary based on the variations in cultural, geopolitical, and health-related contexts. To address these issues, a conjoint ESHRE and Male Reproductive Health Initiative (MRHI) Campus workshop was convened. OBJECTIVE AND RATIONALE The three objectives were: first, to assess the current state of MRH around the world; second, to identify some of the key gaps in knowledge; and, third, to examine how MRH stakeholders can collaboratively generate intelligent and effective paths forward. SEARCH METHODS Each expert reviewed and summarized the current literature that was subsequently used to provide a comprehensive overview of challenges related to MRH. OUTCOMES This narrative report is an overview of the data, opinions, and arguments presented during the workshop. A number of outcomes are presented and can be summarized by the following overarching themes: MRH is a serious global issue and there is a plethora of gaps in our understanding; there is a need for widespread international collaborative networks to undertake multidisciplinary research into fundamental issues, such as lifestyle/environmental exposure studies, and high-quality clinical trials; and there is an urgent requirement for effective strategies to educate young people and the general public to safeguard and improve MRH across diverse population demographics and resources. LIMITATIONS REASONS FOR CAUTION This was a workshop where worldwide leading experts from a wide range of disciplines presented and discussed the evidence regarding challenges related to MRH. While each expert summarized the current literature and placed it in context, the data in a number of areas are limited and/or sparse. Equally, important areas for consideration may have been missed. Moreover, there are clear gaps in our knowledge base, which makes some conclusions necessarily speculative and warranting of further study. WIDER IMPLICATIONS Poor MRH is a global issue that suffers from low awareness among the public, patients, and heathcare professionals. Addressing this will require a coordinated multidisciplinary approach. Addressing the significant number of knowledge gaps will require policy makers prioritizing MRH and its funding. STUDY FUNDING/COMPETING INTERESTS The authors would like to extend their gratitude to ESHRE for providing financial support for the Budapest Campus Workshop, as well as to Microptic S.L. (Barcelona) for kindly sponsoring the workshop. P.B. is the Director of the not-for-profit organization Global Action on Men's Health and receives fees and expenses for his work, (which includes the preparation of this manuscript). Conflicts of interest: C.J.D.J., C.L.R.B., R.A.A., P.B., M.P.C., M.L.E., N.G., N.J., C.K., AAP, M.K.O., S.R.-H., M.H.V.-L.: ESHRE Campus Workshop 2022 (Travel support-personal). C.J.D.J.: Cambridge University Press (book royalties-personal). ESHRE Annual Meeting 2022 and Yale University Panel Meeting 2023 (Travel support-personal). C.L.R.B.: Ferring and IBSA (Lecture), RBMO editor (Honorarium to support travel, etc.), ExSeed and ExScentia (University of Dundee), Bill & Melinda Gates Foundation (for research on contraception). M.P.C.: Previously received funding from pharmaceutical companies for health economic research. The funding was not in relation to this work and had no bearing on the contents of this work. No funding from other sources has been provided in relation to this work (funding was provided to his company Global Market Access Solutions). M.L.E.: Advisor to Ro, Doveras, Next, Hannah, Sandstone. C.K.: European Academy of Andrology (Past president UNPAID), S.K.: CEO of His Turn, a male fertility Diagnostic and Therapeutic company (No payments or profits to date). R.I.M.: www.healthymale.org.au (Australian Government funded not for profit in men's health sector (Employed as Medical Director 0.2 FET), Monash IVF Pty Ltd (Equity holder)). N.J.: Merck (consulting fees), Gedeon Richter (honoraria). S.R.-H.: ESHRE (Travel reimbursements). C.N.: LLC (Nursing educator); COMMIT (Core Outcomes Measures for Infertility Trials) Advisor, meeting attendee, and co-author; COMMA (Core Outcomes in Menopause) Meeting attendee, and co-author; International Federation of Gynecology and Obstetrics (FIGO) Delegate Letters and Sciences; ReproNovo, Advisory board; American Board of Urology Examiner; American Urological Association Journal subsection editor, committee member, guidelines co-author Ferring Scientific trial NexHand Chief Technology Officer, stock ownership Posterity Health Board member, stock ownership. A.P.: Economic and Social Research Council (A collaborator on research grant number ES/W001381/1). Member of an advisory committee for Merck Serono (November 2022), Member of an advisory board for Exceed Health, Speaker fees for educational events organized by Mealis Group; Chairman of the Cryos External Scientific Advisory Committee: All fees associated with this are paid to his former employer The University of Sheffield. Trustee of the Progress Educational Trust (Unpaid). M.K.O.: National Health and Medical Research Council and Australian Research Council (Funding for research of the topic of male fertility), Bill and Melinda Gates Foundation (Funding aimed at the development of male gamete-based contraception), Medical Research Future Fund (Funding aimed at defining the long-term consequences of male infertility). M.H.V.-L.: Department of Sexual and Reproductive Health and Research (SRH)/Human Reproduction Programme (HRP) Research Project Panel RP2/WHO Review Member; MRHI (Core Group Member), COMMIT (member), EGOI (Member); Human Reproduction (Associate Editor), Fertility and Sterility (Editor), AndroLATAM (Founder and Coordinator).
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Affiliation(s)
- Christopher J De Jonge
- Department of Urology, University of Minnesota Medical Center, University of Minnesota, Minneapolis, MN, USA
| | - Christopher L R Barratt
- Division of Systems Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - R John Aitken
- Discipline of Biological Sciences, School of Environment and Life Sciences, College of Engineering, Science and Environment, University of Newcastle, Newcastle, Australia
| | - Richard A Anderson
- MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
| | | | - David Y L Chan
- Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Mark P Connolly
- Health Economics, Global Market Access Solutions LLC, Mooresville, NC, USA
- University Medical Center Groningen, Groningen, The Netherlands
| | - Michael L Eisenberg
- Department of Urology and Obstetrics & Gynecology, Stanford University, Stanford, CA, USA
| | - Nicolas Garrido
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
| | - Niels Jørgensen
- Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Sarah Kimmins
- Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada
- Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, QC, Canada
| | - Csilla Krausz
- Department of Experimental and Clinical Biomedical Sciences, ‘Mario Serio’, University of Florence, University Hospital of Careggi (AOUC), Florence, Italy
| | - Robert I McLachlan
- Hudson Institute of Medical Research, Monash University, Melbourne, Australia
- Monash IVF Group, Cremorne, Australia
| | - Craig Niederberger
- Clarence C. Department of Urology, University of Illinois Chicago (UIC), College of Medicine, Department of Bioengineering, UIC College of Engineering, Chicago, IL,USA
| | - Moira K O’Bryan
- School of BioSciences and Bio21 Institute, The University of Melbourne, Parkville, Australia
| | - Allan Pacey
- Faculty of Biology, Medicine and Health, Core Technology Facility, University of Manchester, Manchester, UK
| | - Lærke Priskorn
- Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | | | - Gamal Serour
- The International Islamic Center for Population Studies and Research, Al-Azhar University, Maadi, Cairo, Egypt
- Egyptian IVF Center, Maadi, Cairo, Egypt
| | - Joris A Veltman
- Faculty of Medical Sciences, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Donna L Vogel
- School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Mónica H Vazquez-Levin
- Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina—Fundación IBYME, Buenos Aires, Argentina
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Grivas TB, Vasiliadis E, Mazioti C, Papagianni D, Mamzeri A, Chandrinos M, Vynichakis G, Athanasopoulos K, Christodoulides P, Jevtic N, Pjanic S, Ljubojevic D, Savvidou O, Kaspiris A, Grunstein J. Are the Spinal Changes in the Course of Scoliogeny Primary but Secondary? J Clin Med 2024; 13:2163. [PMID: 38673436 PMCID: PMC11051170 DOI: 10.3390/jcm13082163] [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: 03/05/2024] [Revised: 04/03/2024] [Accepted: 04/07/2024] [Indexed: 04/28/2024] Open
Abstract
In this opinion article, there is an analysis and discussion regarding the effects of growth on the spinal and rib cage deformities, the role of the rib cage in scoliogeny, the lateral spinal profile in adolescent idiopathic scoliosis (AIS), the genetics and epigenetics of AIS, and the interesting and novel field investigating the sleep impact at nighttime on AIS in relation to the sequence of the scoliogenetic changes in scoliotics. The expressed opinions are mainly based on the published peer-reviewed research of the author and his team of co-authors. Based on the analysis noted above, it can be postulated that the vertebral growth changes in the spine during initial idiopathic scoliosis (IS) development are not primary-intrinsic but secondary changes. The primary cause starting the deformity is not located within the vertebral bodies. Instead, the deformations seen in the vertebral bodies are the secondary effects of asymmetrical loads exerted upon them, due to muscular loads, growth, and gravity.
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Affiliation(s)
- Theodoros B. Grivas
- Trauma and Orthopaedic Department, Former Head, “Tzaneio” General Hospital of Piraeus, 185 36 Piraeus, Greece
| | - Elias Vasiliadis
- 3rd Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, KAT Hospital, 145 61 Athens, Greece; (E.V.); (A.K.)
| | | | | | | | - Michail Chandrinos
- Orthopedic Department, Gen. Hospital of Argolida-N.M. Argous, 212 00 Argos, Greece; (M.C.); (G.V.)
| | - George Vynichakis
- Orthopedic Department, Gen. Hospital of Argolida-N.M. Argous, 212 00 Argos, Greece; (M.C.); (G.V.)
| | | | | | - Nikola Jevtic
- Scolio Centar, 403916 Novi Sad, Serbia; (N.J.); (D.L.)
| | - Samra Pjanic
- Department of Paediatric Rehabilitation, Institute for Physical, Rehabilitation Medicine and Orthopaedic Surgery “Dr Miroslav Zotovic”, 78000 Banja Luka, Bosnia and Herzegovina;
| | | | - Olga Savvidou
- First Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, “ATTIKON” University General Hospital, Rimini 1, 124 62 Athens, Greece;
| | - Angelos Kaspiris
- 3rd Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, KAT Hospital, 145 61 Athens, Greece; (E.V.); (A.K.)
- Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Health Sciences, University of Patras, 265 04 Patras, Greece
| | - Jarrett Grunstein
- Chiropractic Center Livingston, 340 E Northfield Rd # 2E, Livingston, NJ 07039, USA;
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9
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Costa DL. Grandchildren's Longevity and Their Grandfathers' POW Trauma in the U.S. Civil War. Demography 2024; 61:337-361. [PMID: 38393987 PMCID: PMC11813633 DOI: 10.1215/00703370-11191183] [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] [Indexed: 02/25/2024]
Abstract
I document the transmission of a grandfather's net nutritional deprivation and psychosocial stress in young adulthood across multiple generations using the grandfather's ex-prisoner of war (ex-POW) status in the U.S. Civil War (1861-1865). Using a newly created dataset, I uncover an association between a grandfather's ex-POW status and the longevity after age 45 of his sons and male-line grandsons but not of his daughters, granddaughters, female-line grandsons, children-in-law, or grandchildren-in-law. Male-line grandsons lost roughly a year of life at age 45 (4% of remaining life expectancy) if descended from ex-POWs who suffered severe captivity conditions than if descended from non-POWs. If their grandfathers faced a less harsh captivity, male-line grandsons lost less than a year of life compared with those descended from non-POWs. I find that the grandfather's age at exposure and the grandson's education, as well as the son's and the grandson's poor late gestational conditions (proxied by season of birth), mediate this relationship. I rule out socioeconomic status, marriage and mortality selection, and cultural or psychological transmission from grandfathers to grandsons as explanations. I cannot rule out an epigenetic explanation.
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Affiliation(s)
- Dora L Costa
- Department of Economics, University of California, Los Angeles, Los Angeles, CA, USA
- National Bureau of Economic Research, Cambridge, MA, USA
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10
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Rice RC, Gil DV, Baratta AM, Frawley RR, Hill SY, Farris SP, Homanics GE. Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior. Neurobiol Stress 2024; 29:100603. [PMID: 38234394 PMCID: PMC10792982 DOI: 10.1016/j.ynstr.2023.100603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 12/18/2023] [Accepted: 12/19/2023] [Indexed: 01/19/2024] Open
Abstract
Chronic stress and alcohol (ethanol) use are highly interrelated and can change an individual's behavior through molecular adaptations that do not change the DNA sequence, but instead change gene expression. A recent wealth of research has found that these nongenomic changes can be transmitted across generations, which could partially account for the "missing heritability" observed in genome-wide association studies of alcohol use disorder and other stress-related neuropsychiatric disorders. In this review, we summarize the molecular and behavioral outcomes of nongenomic inheritance of chronic stress and ethanol exposure and the germline mechanisms that could give rise to this heritability. In doing so, we outline the need for further research to: (1) Investigate individual germline mechanisms of paternal, maternal, and biparental nongenomic chronic stress- and ethanol-related inheritance; (2) Synthesize and dissect cross-generational chronic stress and ethanol exposure; (3) Determine cross-generational molecular outcomes of preconception ethanol exposure that contribute to alcohol-related disease risk, using cancer as an example. A detailed understanding of the cross-generational nongenomic effects of stress and/or ethanol will yield novel insight into the impact of ancestral perturbations on disease risk across generations and uncover actionable targets to improve human health.
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Affiliation(s)
- Rachel C. Rice
- Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA
| | - Daniela V. Gil
- Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA
| | - Annalisa M. Baratta
- Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA
| | - Remy R. Frawley
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Shirley Y. Hill
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Sean P. Farris
- Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Gregg E. Homanics
- Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA
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11
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Zhang S, Luo Q, Meng R, Yan J, Wu Y, Huang H. Long-term health risk of offspring born from assisted reproductive technologies. J Assist Reprod Genet 2024; 41:527-550. [PMID: 38146031 PMCID: PMC10957847 DOI: 10.1007/s10815-023-02988-5] [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: 06/29/2023] [Accepted: 11/02/2023] [Indexed: 12/27/2023] Open
Abstract
Since the world's first in vitro fertilization baby was born in 1978, there have been more than 8 million children conceived through assisted reproductive technologies (ART) worldwide, and a significant proportion of them have reached puberty or young adulthood. Many studies have found that ART increases the risk of adverse perinatal outcomes, including preterm birth, low birth weight, small size for gestational age, perinatal mortality, and congenital anomalies. However, data regarding the long-term outcomes of ART offspring are limited. According to the developmental origins of health and disease theory, adverse environments during early life stages may induce adaptive changes and subsequently result in an increased risk of diseases in later life. Increasing evidence also suggests that ART offspring are predisposed to an increased risk of non-communicable diseases, such as malignancies, asthma, obesity, metabolic syndrome, diabetes, cardiovascular diseases, and neurodevelopmental and psychiatric disorders. In this review, we summarize the risks for long-term health in ART offspring, discuss the underlying mechanisms, including underlying parental infertility, epigenetic alterations, non-physiological hormone levels, and placental dysfunction, and propose potential strategies to optimize the management of ART and health care of parents and children to eliminate the associated risks. Further ongoing follow-up and research are warranted to determine the effects of ART on the long-term health of ART offspring in later life.
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Affiliation(s)
- Siwei Zhang
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, No. 419, Fangxie Rd, Shanghai, 200011, China
| | - Qinyu Luo
- Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University School of Medicine, Hangzhou, China
| | - Renyu Meng
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, No. 419, Fangxie Rd, Shanghai, 200011, China
| | - Jing Yan
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, No. 419, Fangxie Rd, Shanghai, 200011, China
| | - Yanting Wu
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, No. 419, Fangxie Rd, Shanghai, 200011, China.
- Research Unit of Embryo Original Diseases (No. 2019RU056), Chinese Academy of Medical Sciences, Shanghai, China.
| | - Hefeng Huang
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, No. 419, Fangxie Rd, Shanghai, 200011, China.
- Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University School of Medicine, Hangzhou, China.
- Research Unit of Embryo Original Diseases (No. 2019RU056), Chinese Academy of Medical Sciences, Shanghai, China.
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12
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Costa DL, Lewis C, Yetter N. Children and Grandchildren of Union Army Veterans: New Data Collections to Study the Persistence of Longevity and Socioeconomic Status Across Generations. HISTORICAL METHODS 2024; 56:223-239. [PMID: 38742179 PMCID: PMC11090407 DOI: 10.1080/01615440.2023.2301578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
This paper introduces four new intergenerational and multigenerational datasets which follow both sons and daughters and which can be used to study the persistence of longevity, socioeconomic status, family structure, and geographic mobility across generations. The data follow the children of Black and White Union Army (US Civil War, 1861-5) veterans from birth to death, linking them to the available censuses. The White samples include an over-sample of children of ex-POWs. A separate collection links grandchildren of White Union Army veterans to their death records. The data were created with high quality manual linkage procedures utilizing a wide variety of records to establish links.
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13
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Mason W, Levin AM, Buhl K, Ouchi T, Parker B, Tan J, Ashammakhi N, Jones LR. Translational Research Techniques for the Facial Plastic Surgeon: An Overview. Facial Plast Surg 2023; 39:466-473. [PMID: 37339663 DOI: 10.1055/a-2113-5023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/22/2023] Open
Abstract
The field of facial plastic and reconstructive surgery (FPRS) is an incredibly diverse, multispecialty field that seeks innovative and novel solutions for the management of physical defects on the head and neck. To aid in the advancement of medical and surgical treatments for these defects, there has been a recent emphasis on the importance of translational research. With recent technological advancements, there are now a myriad of research techniques that are widely accessible for physician and scientist use in translational research. Such techniques include integrated multiomics, advanced cell culture and microfluidic tissue models, established animal models, and emerging computer models generated using bioinformatics. This study discusses these various research techniques and how they have and can be used for research in the context of various important diseases within the field of FPRS.
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Affiliation(s)
- William Mason
- Department of Otolaryngology, Henry Ford Hospital, Detroit, Michigan
| | - Albert M Levin
- Department of Public Health Science, Henry Ford Health, Detroit, Michigan
- Center for Bioinformatics, Henry Ford Health, Detroit, Michigan
| | - Katherine Buhl
- Department of Otolaryngology, Henry Ford Hospital, Detroit, Michigan
| | - Takahiro Ouchi
- Department of Otolaryngology, Henry Ford Hospital, Detroit, Michigan
| | - Bianca Parker
- Department of Otolaryngology, Henry Ford Hospital, Detroit, Michigan
| | - Jessica Tan
- Department of Otolaryngology, Henry Ford Hospital, Detroit, Michigan
| | - Nureddin Ashammakhi
- Institute for Quantitative Health Science and Engineering, Michigan State University, Michigan
- Department of Biomedical Engineering, College of Engineering, Michigan State University, Michigan
- College of Human Medicine, Michigan State University, Michigan
| | - Lamont R Jones
- Department of Otolaryngology, Henry Ford Hospital, Detroit, Michigan
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14
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Costa DL. Overweight grandsons and grandfathers' starvation exposure. JOURNAL OF HEALTH ECONOMICS 2023; 91:102796. [PMID: 37541079 PMCID: PMC10593129 DOI: 10.1016/j.jhealeco.2023.102796] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 07/08/2023] [Accepted: 07/10/2023] [Indexed: 08/06/2023]
Abstract
Much of the increase in the prevalence of overweight and obesity has been in developing countries with a history of famines and malnutrition. This paper is the first to examine overweight among adult grandsons of grandfathers exposed to starvation during developmental ages. I study grandsons born to grandfathers who served in the Union Army during the US Civil War (1861-5) where some grandfathers experienced severe net malnutrition because they suffered a harsh POW experience. I find that male-line but not female-line grandsons of grandfathers who survived a severe captivity during their growing years faced a 21% increase in mean overweight and a 2% increase in mean BMI compared to grandsons of non-POWs. Male-line grandsons descended from grandfathers who experienced a harsh captivity faced a 22%-28% greater risk of dying every year after age 45 relative to grandsons descended from non-POWs, with overweight accounting for 9%-14% of the excess risk.
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Affiliation(s)
- Dora L Costa
- University of California, Los Angeles, United States of America; National Bureau of Economic Research, United States of America.
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15
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Mc Auley MT. An evolutionary perspective of lifespan and epigenetic inheritance. Exp Gerontol 2023; 179:112256. [PMID: 37460026 DOI: 10.1016/j.exger.2023.112256] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 07/04/2023] [Accepted: 07/12/2023] [Indexed: 07/21/2023]
Abstract
In the last decade epigenetics has come to the fore as a discipline which is central to biogerontology. Age associated epigenetic changes are routinely linked with pathologies, including cardiovascular disease, cancer, and Alzheimer's disease; moreover, epigenetic clocks are capable of correlating biological age with chronological age in many species including humans. Recent intriguing empirical observations also suggest that inherited epigenetic effects could influence lifespan/longevity in a variety of organisms. If this is the case, an imperative exists to reconcile lifespan/longevity associated inherited epigenetic processes with the evolution of ageing. This review will critically evaluate inherited epigenetic effects from an evolutionary perspective. The overarching aim is to integrate the evidence which suggests epigenetic inheritance modulates lifespan/longevity with the main evolutionary theories of ageing.
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16
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Zhu H, Ding G, Liu X, Huang H. Developmental origins of diabetes mellitus: Environmental epigenomics and emerging patterns. J Diabetes 2023. [PMID: 37190864 DOI: 10.1111/1753-0407.13403] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 01/09/2023] [Accepted: 04/22/2023] [Indexed: 05/17/2023] Open
Abstract
Mounting epidemiological evidence indicates that environmental exposures in early life have roles in diabetes susceptibility in later life. Additionally, environmentally induced diabetic susceptibility could be transmitted to subsequent generations. Epigenetic modifications provide a potential association with the environmental factors and altered gene expression that might cause disease phenotypes. Here, we bring the increasing evidence that environmental exposures early in development are linked to diabetes through epigenetic modifications. This review first summarizes the epigenetic targets, including metastable epialleles and imprinting genes, by which the environmental factors can modify the epigenome. Then we review the epigenetics changes in response to environmental challenge during critical developmental windows, gametogenesis, embryogenesis, and fetal and postnatal period, with the specific example of diabetic susceptibility. Although the mechanisms are still largely unknown, especially in humans, the new research methods are now gradually available, and the animal models can provide more in-depth study of mechanisms. These have implications for investigating the link of the phenomena to human diabetes, providing a new perspective on environmentally triggered diabetes risk.
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Affiliation(s)
- Hong Zhu
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China
| | - Guolian Ding
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China
| | - Xinmei Liu
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China
| | - Hefeng Huang
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China
- Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University School of Medicine, Hangzhou, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
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17
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Lismer A, Kimmins S. Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development. Nat Commun 2023; 14:2142. [PMID: 37059740 PMCID: PMC10104880 DOI: 10.1038/s41467-023-37820-2] [Citation(s) in RCA: 59] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 03/31/2023] [Indexed: 04/16/2023] Open
Abstract
Although more studies are demonstrating that a father's environment can influence child health and disease, the molecular mechanisms underlying non-genetic inheritance remain unclear. It was previously thought that sperm exclusively contributed its genome to the egg. More recently, association studies have shown that various environmental exposures including poor diet, toxicants, and stress, perturbed epigenetic marks in sperm at important reproductive and developmental loci that were associated with offspring phenotypes. The molecular and cellular routes that underlie how epigenetic marks are transmitted at fertilization, to resist epigenetic reprogramming in the embryo, and drive phenotypic changes are only now beginning to be unraveled. Here, we provide an overview of the state of the field of intergenerational paternal epigenetic inheritance in mammals and present new insights into the relationship between embryo development and the three pillars of epigenetic inheritance: chromatin, DNA methylation, and non-coding RNAs. We evaluate compelling evidence of sperm-mediated transmission and retention of paternal epigenetic marks in the embryo. Using landmark examples, we discuss how sperm-inherited regions may escape reprogramming to impact development via mechanisms that implicate transcription factors, chromatin organization, and transposable elements. Finally, we link paternally transmitted epigenetic marks to functional changes in the pre- and post-implantation embryo. Understanding how sperm-inherited epigenetic factors influence embryo development will permit a greater understanding related to the developmental origins of health and disease.
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Affiliation(s)
- Ariane Lismer
- Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, H3G 1Y6, Canada
| | - Sarah Kimmins
- Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, H3G 1Y6, Canada.
- Department of Pathology and Cell Biology, Faculty of Medicine, University of Montreal Hospital Research Centre, Montreal, QC, H2X 0A9, Canada.
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18
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González-Rodríguez P, Füllgrabe J, Joseph B. The hunger strikes back: an epigenetic memory for autophagy. Cell Death Differ 2023:10.1038/s41418-023-01159-4. [PMID: 37031275 DOI: 10.1038/s41418-023-01159-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 03/24/2023] [Accepted: 03/28/2023] [Indexed: 04/10/2023] Open
Abstract
Historical and demographical human cohorts of populations exposed to famine, as well as animal studies, revealed that exposure to food deprivation is associated to lasting health-related effects for the exposed individuals, as well as transgenerational effects in their offspring that affect their diseases' risk and overall longevity. Autophagy, an evolutionary conserved catabolic process, serves as cellular response to cope with nutrient starvation, allowing the mobilization of an internal source of stored nutrients and the production of energy. We review the evidence obtained in multiple model organisms that support the idea that autophagy induction, including through dietary regimes based on reduced food intake, is in fact associated to improved health span and extended lifespan. Thereafter, we expose autophagy-induced chromatin remodeling, such as DNA methylation and histone posttranslational modifications that are known heritable epigenetic marks, as a plausible mechanism for transgenerational epigenetic inheritance of hunger.
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Affiliation(s)
- Patricia González-Rodríguez
- Division of Biochemistry, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
- Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Jens Füllgrabe
- Cambridge Epigenetix Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK
| | - Bertrand Joseph
- Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden.
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19
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Abstract
BACKGROUND Autoimmune hepatitis has an unknown cause and genetic associations that are not disease-specific or always present. Clarification of its missing causality and heritability could improve prevention and management strategies. AIMS Describe the key epigenetic and genetic mechanisms that could account for missing causality and heritability in autoimmune hepatitis; indicate the prospects of these mechanisms as pivotal factors; and encourage investigations of their pathogenic role and therapeutic potential. METHODS English abstracts were identified in PubMed using multiple key search phases. Several hundred abstracts and 210 full-length articles were reviewed. RESULTS Environmental induction of epigenetic changes is the prime candidate for explaining the missing causality of autoimmune hepatitis. Environmental factors (diet, toxic exposures) can alter chromatin structure and the production of micro-ribonucleic acids that affect gene expression. Epistatic interaction between unsuspected genes is the prime candidate for explaining the missing heritability. The non-additive, interactive effects of multiple genes could enhance their impact on the propensity and phenotype of autoimmune hepatitis. Transgenerational inheritance of acquired epigenetic marks constitutes another mechanism of transmitting parental adaptations that could affect susceptibility. Management strategies could range from lifestyle adjustments and nutritional supplements to precision editing of the epigenetic landscape. CONCLUSIONS Autoimmune hepatitis has a missing causality that might be explained by epigenetic changes induced by environmental factors and a missing heritability that might reflect epistatic gene interactions or transgenerational transmission of acquired epigenetic marks. These unassessed or under-evaluated areas warrant investigation.
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Affiliation(s)
- Albert J Czaja
- Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
- Professor Emeritus of Medicine, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN, 55905, USA.
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20
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Ribas-Aulinas F, Ribo S, Casas E, Mourin-Fernandez M, Ramon-Krauel M, Diaz R, Lerin C, Kalko SG, Vavouri T, Jimenez-Chillaron JC. Intergenerational Inheritance of Hepatic Steatosis in a Mouse Model of Childhood Obesity: Potential Involvement of Germ-Line microRNAs. Nutrients 2023; 15:nu15051241. [PMID: 36904241 PMCID: PMC10005268 DOI: 10.3390/nu15051241] [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: 01/10/2023] [Revised: 02/23/2023] [Accepted: 02/27/2023] [Indexed: 03/05/2023] Open
Abstract
Childhood obesity increases the risk of developing metabolic syndrome later in life. Moreover, metabolic dysfunction may be inherited into the following generation through non-genomic mechanisms, with epigenetics as a plausible candidate. The pathways involved in the development of metabolic dysfunction across generations in the context of childhood obesity remain largely unexplored. We have developed a mouse model of early adiposity by reducing litter size at birth (small litter group, SL: 4 pups/dam; control group, C: 8 pups/dam). Mice raised in small litters (SL) developed obesity, insulin resistance and hepatic steatosis with aging. Strikingly, the offspring of SL males (SL-F1) also developed hepatic steatosis. Paternal transmission of an environmentally induced phenotype strongly suggests epigenetic inheritance. We analyzed the hepatic transcriptome in C-F1 and SL-F1 mice to identify pathways involved in the development of hepatic steatosis. We found that the circadian rhythm and lipid metabolic process were the ontologies with highest significance in the liver of SL-F1 mice. We explored whether DNA methylation and small non-coding RNAs might be involved in mediating intergenerational effects. Sperm DNA methylation was largely altered in SL mice. However, these changes did not correlate with the hepatic transcriptome. Next, we analyzed small non-coding RNA content in the testes of mice from the parental generation. Two miRNAs (miR-457 and miR-201) appeared differentially expressed in the testes of SL-F0 mice. They are known to be expressed in mature spermatozoa, but not in oocytes nor early embryos, and they may regulate the transcription of lipogenic genes, but not clock genes, in hepatocytes. Hence, they are strong candidates to mediate the inheritance of adult hepatic steatosis in our murine model. In conclusion, litter size reduction leads to intergenerational effects through non-genomic mechanisms. In our model, DNA methylation does not seem to play a role on the circadian rhythm nor lipid genes. However, at least two paternal miRNAs might influence the expression of a few lipid-related genes in the first-generation offspring, F1.
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Affiliation(s)
| | - Sílvia Ribo
- Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues, 08950 Barcelona, Spain
| | - Eduard Casas
- Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Spain
| | | | - Marta Ramon-Krauel
- Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues, 08950 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Ruben Diaz
- Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues, 08950 Barcelona, Spain
| | - Carles Lerin
- Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues, 08950 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Susana G. Kalko
- Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain
| | - Tanya Vavouri
- Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Spain
| | - Josep C. Jimenez-Chillaron
- Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues, 08950 Barcelona, Spain
- School of Medicine, University of Barcelona, L’Hospitalet, 08907 Barcelona, Spain
- Correspondence: or ; Tel.: +34-934024267
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21
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Yao WY, Li L, Jiang HR, Yu YF, Xu WH. Transgenerational associations of parental famine exposure in early life with offspring risk of adult obesity in China. Obesity (Silver Spring) 2023; 31:279-289. [PMID: 36507560 DOI: 10.1002/oby.23593] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 08/08/2022] [Accepted: 08/31/2022] [Indexed: 12/14/2022]
Abstract
OBJECTIVE The aim of this study was to investigate the transgenerational associations between exposure to famine in early life and obesity. METHODS This study used the longitudinal data from the China Health and Nutrition Survey from 1989 to 2015. A total of 1113 fathers and 1207 mothers (946 mother-father pairs) born in 1955 to 1966 and 1895 adult offspring were included. Offspring were classified into subgroups according to the famine exposure of their parents (unexposed, maternal exposed, paternal exposed, parental exposed) and exposure timing (during fetal development, childhood). RESULTS Maternal exposure to famine in early life was associated with elevated levels of BMI, waist circumference, overweight, and central obesity of their children, whereas paternal exposure was inversely associated with these measurements. Compared with children of unexposed parents (P0M0), the maternal exposed group (P0M1) had higher mean BMI, by 1.3 kg/m2 (95% CI: 0.3 to 2.4); waist circumference, by 1.5 cm (-1.0 to 3.9); overweight (odds ratio [OR] [95% CI]: 3.1 [1.6 to 6.1]); and central obesity (OR [95% CI]: 1.9 [1.02 to 3.7]). No significant heterogeneity was observed in the associations by sex of offspring. CONCLUSIONS Fetal and early childhood exposure to famine in parents may be associated with their children's risk of obesity during adulthood. A better understanding of the transgenerational associations is important for developing strategies to reduce obesity risk in future generations.
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Affiliation(s)
- Wei-Yuan Yao
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China
- Yiwu Research Institite, Fudan University, Yiwu, China
| | - Leah Li
- Population, Policy and Practice Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Hui-Ru Jiang
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China
| | - Yong-Fu Yu
- Department of Biostatistics, School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China
| | - Wang-Hong Xu
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China
- Yiwu Research Institite, Fudan University, Yiwu, China
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22
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Food abundance in men before puberty predicts a range of cancers in grandsons. Nat Commun 2022; 13:7507. [PMID: 36473854 PMCID: PMC9726939 DOI: 10.1038/s41467-022-35217-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 11/23/2022] [Indexed: 12/12/2022] Open
Abstract
Nutritional conditions early in human life may influence phenotypic characteristics in later generations. A male-line transgenerational pathway, triggered by the early environment, has been postulated with support from animal and a small number of human studies. Here we analyse individuals born in Uppsala Sweden 1915-29 with linked data from their children and parents, which enables us to explore the hypothesis that pre-pubertal food abundance may trigger a transgenerational effect on cancer events. We used cancer registry and cause-of-death data to analyse 3422 cancer events in grandchildren (G2) by grandparental (G0) food access. We show that variation in harvests and food access in G0 predicts cancer occurrence in G2 in a specific way: abundance among paternal grandfathers, but not any other grandparent, predicts cancer occurrence in grandsons but not in granddaughters. This male-line response is observed for several groups of cancers, suggesting a general susceptibility, possibly acquired in early embryonic development. We observed no transgenerational influence in the middle generation.
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23
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Comas-Armangue G, Makharadze L, Gomez-Velazquez M, Teperino R. The Legacy of Parental Obesity: Mechanisms of Non-Genetic Transmission and Reversibility. Biomedicines 2022; 10:biomedicines10102461. [PMID: 36289722 PMCID: PMC9599218 DOI: 10.3390/biomedicines10102461] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 09/21/2022] [Accepted: 09/23/2022] [Indexed: 11/27/2022] Open
Abstract
While a dramatic increase in obesity and related comorbidities is being witnessed, the underlying mechanisms of their spread remain unresolved. Epigenetic and other non-genetic mechanisms tend to be prominent candidates involved in the establishment and transmission of obesity and associated metabolic disorders to offspring. Here, we review recent findings addressing those candidates, in the context of maternal and paternal influences, and discuss the effectiveness of preventive measures.
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Affiliation(s)
- Gemma Comas-Armangue
- German Research Center for Environmental Health Neuherberg, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany
- German Center for Diabetes Research (DZD) Neuherberg, 85764 Neuherberg, Germany
| | - Lela Makharadze
- German Research Center for Environmental Health Neuherberg, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany
- German Center for Diabetes Research (DZD) Neuherberg, 85764 Neuherberg, Germany
| | - Melisa Gomez-Velazquez
- German Research Center for Environmental Health Neuherberg, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany
- German Center for Diabetes Research (DZD) Neuherberg, 85764 Neuherberg, Germany
- Correspondence: (M.G.-V.); (R.T.)
| | - Raffaele Teperino
- German Research Center for Environmental Health Neuherberg, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany
- German Center for Diabetes Research (DZD) Neuherberg, 85764 Neuherberg, Germany
- Correspondence: (M.G.-V.); (R.T.)
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24
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Alt KW, Al-Ahmad A, Woelber JP. Nutrition and Health in Human Evolution-Past to Present. Nutrients 2022; 14:3594. [PMID: 36079850 PMCID: PMC9460423 DOI: 10.3390/nu14173594] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 11/23/2022] Open
Abstract
Anyone who wants to understand the biological nature of humans and their special characteristics must look far back into evolutionary history. Today's way of life is drastically different from that of our ancestors. For almost 99% of human history, gathering and hunting have been the basis of nutrition. It was not until about 12,000 years ago that humans began domesticating plants and animals. Bioarchaeologically and biochemically, this can be traced back to our earliest roots. Modern living conditions and the quality of human life are better today than ever before. However, neither physically nor psychosocially have we made this adjustment and we are paying a high health price for it. The studies presented allow us to reconstruct food supply, lifestyles, and dietary habits: from the earliest primates, through hunter-gatherers of the Paleolithic, farming communities since the beginning of the Anthropocene, to the Industrial Age and the present. The comprehensive data pool allows extraction of all findings of medical relevance. Our recent lifestyle and diet are essentially determined by our culture rather than by our millions of years of ancestry. Culture is permanently in a dominant position compared to natural evolution. Thereby culture does not form a contrast to nature but represents its result. There is no doubt that we are biologically adapted to culture, but it is questionable how much culture humans can cope with.
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Affiliation(s)
- Kurt W. Alt
- Center of Natural and Cultural Human History, Danube Private University, 3500 Krems, Austria
- Integrative Prehistory and Archaeological Science, University of Basel, 4055 Basel, Switzerland
| | - Ali Al-Ahmad
- Department of Operative Dentistry and Periodontology, Faculty of Medicine, University of Freiburg, 71906 Freiburg, Germany
| | - Johan Peter Woelber
- Department of Operative Dentistry and Periodontology, Faculty of Medicine, University of Freiburg, 71906 Freiburg, Germany
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25
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Liu Y, Liu Y, Lu Y, Li J, He S. Association of Parental Famine Exposure With Offspring Depression and Cognition Function. Front Psychiatry 2022; 13:812805. [PMID: 35449569 PMCID: PMC9016118 DOI: 10.3389/fpsyt.2022.812805] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 03/09/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The effect of early exposure to famine on depression and cognition in adulthood has been shown, but the intergenerational association of famine remain to be explored. This study focused on exploring the association of parental famine exposure with depression and cognition in the offspring. METHODS Based on the Chinese Family Panel Studies database, which is a longitudinal survey, we included 5,150 individuals born between 1959 and 1961 and divided them into fetal-exposed, infancy-exposed (birth year = 1957-1958), school-age-exposed (birth year = 1949-1956), adolescent-exposed (birth year = 1946-1948), and unexposed groups. We used one-way analysis of variance, multiple linear regression, and one follow-up measurement to analyze the association between parental famine exposure and offspring depression and cognitive function. RESULTS Compared with the unexposed group, the correlations between parental famine exposure during fetal period and their cognitive function (mother: β = -1.614, 95% CI: -2.535, -0.693; p = 0.001; father: β = -2.153, 95% CI: -3.104, -1.202, p < 0.001) were significant. For the offspring, there was a negative correlation between famine exposure of fathers during the fetal period and depression in their offspring (β = -0.477, 95% CI: -0.907, -0.047; p = 0.030). There was a negative correlation between maternal famine exposure during the infant and adolescent period and cognitive function in the offspring (math test: β = -0.730, 95% CI: -1.307, -0.153; p = 0.013; word test: β = -2.346, 95% CI: -4.067, -0.625; p = 0.008). LIMITATIONS Not all variables related to depression and cognition function were included in the CFPS database, and the other unknown or unmeasured confounders may explain our results.
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Affiliation(s)
- Ye Liu
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Ningxia Medical University, Yinchuan, China
| | - Yu Liu
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Ningxia Medical University, Yinchuan, China
| | - Yuzhu Lu
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Ningxia Medical University, Yinchuan, China
| | - Jiangping Li
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Ningxia Medical University, Yinchuan, China.,Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan, China
| | - Shulan He
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Ningxia Medical University, Yinchuan, China.,Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan, China
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26
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Pool KR, Chazal F, Smith JT, Blache D. Estrogenic Pastures: A Source of Endocrine Disruption in Sheep Reproduction. Front Endocrinol (Lausanne) 2022; 13:880861. [PMID: 35574027 PMCID: PMC9097266 DOI: 10.3389/fendo.2022.880861] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 03/25/2022] [Indexed: 11/13/2022] Open
Abstract
Phytoestrogens can impact on reproductive health due to their structural similarity to estradiol. Initially identified in sheep consuming estrogenic pasture, phytoestrogens are known to influence reproductive capacity in numerous species. Estrogenic pastures continue to persist in sheep production systems, yet there has been little headway in our understanding of the underlying mechanisms that link phytoestrogens with compromised reproduction in sheep. Here we review the known and postulated actions of phytoestrogens on reproduction, with particular focus on competitive binding with nuclear and non-nuclear estrogen receptors, modifications to the epigenome, and the downstream impacts on normal physiological function. The review examines the evidence that phytoestrogens cause reproductive dysfunction in both the sexes, and that outcomes depend on the developmental period when an individual is exposed to phytoestrogen.
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27
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Lin PZ, Meissner CM. Persistent Pandemics. ECONOMICS AND HUMAN BIOLOGY 2021; 43:101044. [PMID: 34371338 PMCID: PMC8285223 DOI: 10.1016/j.ehb.2021.101044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 04/22/2021] [Accepted: 07/06/2021] [Indexed: 06/13/2023]
Abstract
We ask whether mortality from historical pandemics has any predictive content for mortality in the Covid-19 pandemic. We find strong persistence in public health performance. Places that performed worse in terms of mortality in the 1918 influenza pandemic also have higher Covid-19 mortality today. This is true across countries as well as across a sample of large US cities. Experience with SARS in 2003 is associated with slightly lower mortality today. We discuss some socio-political factors that may account for persistence including distrust of expert advice, lack of cooperation, over-confidence, and health care supply shortages. Multi-generational effects of past pandemics may also matter.
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Affiliation(s)
- Peter Z Lin
- California Center for Population Research, University of California, Los Angeles, United States.
| | - Christopher M Meissner
- Department of Economics, University of California, Davis and National Bureau of Economic Research (NBER), United States.
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28
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Brown SG, Brenman-Suttner DB, McInnes AG, Lew K, Moehring AJ, Bauer JH, Simon AF. Inheritance of pheromone profiles from aged D. melanogaster. MICROPUBLICATION BIOLOGY 2021; 2021:10.17912/micropub.biology.000459. [PMID: 34723148 PMCID: PMC8553430 DOI: 10.17912/micropub.biology.000459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/24/2021] [Accepted: 09/24/2021] [Indexed: 12/02/2022]
Abstract
Through aging, D. melanogaster males and females change their social spacing. Flies are initially more social, but reduce sociability as they grow older. This preferred social space is inherited in their progeny. Here, we report that in females, the profiles of cuticular hydrocarbons (CHC), which are known to promote social interaction between individuals, similarly are affected by age. Importantly, for a subset of those CHC, the progeny's CHC levels are comparable to those of their parents, suggesting that parental age influences offspring CHC expression. Those data establish a foundation to identify the relationship between CHC levels and social spacing, and to understand the mechanisms of the inheritance of complex traits.
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Affiliation(s)
- Samuel G Brown
- Department of Chemistry, California State University Sacramento, CA, USA
| | - Dova B Brenman-Suttner
- Current: Department of Biology, York University, Toronto, ON, Canada,
Department of Biology, University of Western Ontario, London, ON, Canada
| | - Abigail G McInnes
- Department of Chemistry, California State University Sacramento, CA, USA
| | - Katlynn Lew
- Department of Chemistry, California State University Sacramento, CA, USA
| | - Amanda J Moehring
- Department of Biology, University of Western Ontario, London, ON, Canada
| | - Johannes H Bauer
- Department of Chemistry, California State University Sacramento, CA, USA
| | - Anne F Simon
- Department of Biology, University of Western Ontario, London, ON, Canada,
Correspondence to: Anne F Simon ()
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29
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Tavares RS, Ramalho-Santos J. The role of sperm and oocyte in fetal programming: Is Lamarck making a comeback? Eur J Clin Invest 2021; 51:e13521. [PMID: 33587759 DOI: 10.1111/eci.13521] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/21/2021] [Accepted: 02/09/2021] [Indexed: 12/23/2022]
Abstract
Compelling evidence has shown that parental experiences and age at conception may potentially shape the future health of the next generation(s). Certain factors may affect both the female and, strikingly, the male gametes potentially causing the transmission of acquired traits, which was strongly defended by Jean-Baptiste Lamarck. Neurodevelopmental psychiatric disorders, trinucleotide repeat-associated diseases, cardiovascular pathologies, diabetes, obesity and cancer in the offspring, among others, have now been associated with events occurring at the preconception level. The potential implications of a (trans)generational inheritance of parental disease and exposure effects should be taken into account in counselling and public policy. Further research into how exactly gametes apparently deliver more than DNA to a new generation is warranted.
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Affiliation(s)
- Renata Santos Tavares
- CNC-Center for Neuroscience and Cell Biology, CIBB, Azinhaga de Santa Comba, Polo 3, University of Coimbra, Coimbra, Portugal.,IIIUC-Institute for Interdisciplinary Research, Casa Costa Alemão, University of Coimbra, Coimbra, Portugal
| | - João Ramalho-Santos
- CNC-Center for Neuroscience and Cell Biology, CIBB, Azinhaga de Santa Comba, Polo 3, University of Coimbra, Coimbra, Portugal.,Department of Life Sciences, University of Coimbra, Coimbra, Portugal
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30
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Martynyuk AE, Ju LS, Morey TE. The potential role of stress and sex steroids in heritable effects of sevoflurane†. Biol Reprod 2021; 105:735-746. [PMID: 34192761 PMCID: PMC8444702 DOI: 10.1093/biolre/ioab129] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/17/2021] [Accepted: 06/25/2021] [Indexed: 12/11/2022] Open
Abstract
Most surgical procedures require general anesthesia, which is a reversible deep sedation state lacking all perception. The induction of this state is possible because of complex molecular and neuronal network actions of general anesthetics (GAs) and other pharmacological agents. Laboratory and clinical studies indicate that the effects of GAs may not be completely reversible upon anesthesia withdrawal. The long-term neurocognitive effects of GAs, especially when administered at the extremes of ages, are an increasingly recognized health concern and the subject of extensive laboratory and clinical research. Initial studies in rodents suggest that the adverse effects of GAs, whose actions involve enhancement of GABA type A receptor activity (GABAergic GAs), can also extend to future unexposed offspring. Importantly, experimental findings show that GABAergic GAs may induce heritable effects when administered from the early postnatal period to at least young adulthood, covering nearly all age groups that may have children after exposure to anesthesia. More studies are needed to understand when and how the clinical use of GAs in a large and growing population of patients can result in lower resilience to diseases in the even larger population of their unexposed offspring. This minireview is focused on the authors' published results and data in the literature supporting the notion that GABAergic GAs, in particular sevoflurane, may upregulate systemic levels of stress and sex steroids and alter expressions of genes that are essential for the functioning of these steroid systems. The authors hypothesize that stress and sex steroids are involved in the mediation of sex-specific heritable effects of sevoflurane.
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Affiliation(s)
- Anatoly E Martynyuk
- Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA
- McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA
| | - Ling-Sha Ju
- Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA
| | - Timothy E Morey
- Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA
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31
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Merrill SM, Moore SR, Gladish N, Giesbrecht GF, Dewey D, Konwar C, MacIssac JL, Kobor MS, Letourneau NL. Paternal adverse childhood experiences: Associations with infant DNA methylation. Dev Psychobiol 2021; 63:e22174. [PMID: 34333774 DOI: 10.1002/dev.22174] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 06/17/2021] [Accepted: 06/24/2021] [Indexed: 12/14/2022]
Abstract
Adverse childhood experiences (ACEs), or cumulative childhood stress exposures, such as abuse, neglect, and household dysfunction, predict later health problems in both the exposed individuals and their offspring. One potential explanation suggests exposure to early adversity predicts epigenetic modification, especially DNA methylation (DNAm), linked to later health. Stress experienced preconception by mothers may associate with DNAm in the next generation. We hypothesized that fathers' exposure to ACEs also associates with their offspring DNAm, which, to our knowledge, has not been previously explored. An epigenome-wide association study (EWAS) of blood DNAm (n = 45) from 3-month-old infants was regressed onto fathers' retrospective ACEs at multiple Cytosine-phosphate-Guanosine (CpG) sites to discover associations. This accounted for infants' sex, age, ethnicity, cell type proportion, and genetic variability. Higher ACE scores associated with methylation values at eight CpGs. Post-hoc analysis found no contribution of paternal education, income, marital status, and parental postpartum depression, but did with paternal smoking and BMI along with infant sleep latency. These same CpGs also contributed to the association between paternal ACEs and offspring attention problems at 3 years. Collectively, these findings suggested there were biological associations with paternal early life adversity and offspring DNAm in infancy, potentially affecting offspring later childhood outcomes.
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Affiliation(s)
- Sarah M Merrill
- BC Children's Hospital Research Institute Vancouver, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
| | - Sarah R Moore
- BC Children's Hospital Research Institute Vancouver, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
| | - Nicole Gladish
- BC Children's Hospital Research Institute Vancouver, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
| | - Gerald F Giesbrecht
- Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.,Owerko Centre at the Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Deborah Dewey
- Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.,Owerko Centre at the Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.,Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Chaini Konwar
- BC Children's Hospital Research Institute Vancouver, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
| | - Julia L MacIssac
- BC Children's Hospital Research Institute Vancouver, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
| | - Michael S Kobor
- BC Children's Hospital Research Institute Vancouver, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.,Program in Child and Brain Development, CIFAR, Toronto, Ontario, Canada
| | - Nicole L Letourneau
- Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.,Owerko Centre at the Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.,Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.,Faculty of Nursing, University of Calgary, Calgary, Alberta, Canada
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32
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Gagliardi L, Williams TC. Commentary: Descent from the aerial palace. Int J Epidemiol 2021; 49:1870-1873. [PMID: 33279998 DOI: 10.1093/ije/dyaa206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2020] [Indexed: 11/14/2022] Open
Affiliation(s)
- Luigi Gagliardi
- Division of Neonatology and Pediatrics, Ospedale Versilia, Viareggio, Azienda USL Toscana Nord Ovest, Pisa, Italy
| | - Thomas C Williams
- MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, UK
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33
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Griñán-Ferré C, Bellver-Sanchis A, Izquierdo V, Corpas R, Roig-Soriano J, Chillón M, Andres-Lacueva C, Somogyvári M, Sőti C, Sanfeliu C, Pallàs M. The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer's disease pathology: From antioxidant to epigenetic therapy. Ageing Res Rev 2021; 67:101271. [PMID: 33571701 DOI: 10.1016/j.arr.2021.101271] [Citation(s) in RCA: 139] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 02/03/2021] [Accepted: 02/03/2021] [Indexed: 12/12/2022]
Abstract
While the elderly segment of the population continues growing in importance, neurodegenerative diseases increase exponentially. Lifestyle factors such as nutrition, exercise, and education, among others, influence ageing progression, throughout life. Notably, the Central Nervous System (CNS) can benefit from nutritional strategies and dietary interventions that prevent signs of senescence, such as cognitive decline or neurodegenerative diseases such as Alzheimer's disease and Parkinson's Disease. The dietary polyphenol Resveratrol (RV) possesses antioxidant and cytoprotective effects, producing neuroprotection in several organisms. The oxidative stress (OS) occurs because of Reactive oxygen species (ROS) accumulation that has been proposed to explain the cause of the ageing. One of the most harmful effects of ROS in the cell is DNA damage. Nevertheless, there is also evidence demonstrating that OS can produce other molecular changes such as mitochondrial dysfunction, inflammation, apoptosis, and epigenetic modifications, among others. Interestingly, the dietary polyphenol RV is a potent antioxidant and possesses pleiotropic actions, exerting its activity through various molecular pathways. In addition, recent evidence has shown that RV mediates epigenetic changes involved in ageing and the function of the CNS that persists across generations. Furthermore, it has been demonstrated that RV interacts with gut microbiota, showing modifications in bacterial composition associated with beneficial effects. In this review, we give a comprehensive overview of the main mechanisms of action of RV in different experimental models, including clinical trials and discuss how the interconnection of these molecular events could explain the neuroprotective effects induced by RV.
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Affiliation(s)
- Christian Griñán-Ferré
- Pharmacology Section, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona (NeuroUB), Av Joan XXIII 27-31, 08028, Barcelona, Spain.
| | - Aina Bellver-Sanchis
- Pharmacology Section, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona (NeuroUB), Av Joan XXIII 27-31, 08028, Barcelona, Spain
| | - Vanessa Izquierdo
- Pharmacology Section, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona (NeuroUB), Av Joan XXIII 27-31, 08028, Barcelona, Spain
| | - Rubén Corpas
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC, IDIBAPS and CIBERESP, Barcelona, Spain
| | - Joan Roig-Soriano
- Department of Biochemistry and Molecular Biology, Universitat Autònoma Barcelona, Institut de Neurociènces (INc), Universitat Autònoma Barcelona, Bellaterra, Spain
| | - Miguel Chillón
- Department of Biochemistry and Molecular Biology, Universitat Autònoma Barcelona, Institut de Neurociènces (INc), Universitat Autònoma Barcelona, Bellaterra, Spain; Vall d'Hebron Institut de Recerca (VHIR), Research Group on Gene Therapy at Nervous System, Passeig de la Vall d'Hebron, Barcelona, Spain; Unitat producció de Vectors (UPV), Universitat Autònoma Barcelona, Bellaterra, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
| | - Cristina Andres-Lacueva
- Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Xarta, INSA, Faculty of Pharmacy and Food Sciences, Campus Torribera, University of Barcelona, Spain; CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salut Carlos III, Barcelona, Spain
| | - Milán Somogyvári
- Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
| | - Csaba Sőti
- Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
| | - Coral Sanfeliu
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC, IDIBAPS and CIBERESP, Barcelona, Spain
| | - Mercè Pallàs
- Pharmacology Section, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona (NeuroUB), Av Joan XXIII 27-31, 08028, Barcelona, Spain
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Maurice C, Dalvai M, Lambrot R, Deschênes A, Scott-Boyer MP, McGraw S, Chan D, Côté N, Ziv-Gal A, Flaws JA, Droit A, Trasler J, Kimmins S, Bailey JL. Early-Life Exposure to Environmental Contaminants Perturbs the Sperm Epigenome and Induces Negative Pregnancy Outcomes for Three Generations via the Paternal Lineage. EPIGENOMES 2021; 5:epigenomes5020010. [PMID: 34968297 PMCID: PMC8594730 DOI: 10.3390/epigenomes5020010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 04/27/2021] [Indexed: 12/13/2022] Open
Abstract
Due to the grasshopper effect, the Arctic food chain in Canada is contaminated with persistent organic pollutants (POPs) of industrial origin, including polychlorinated biphenyls and organochlorine pesticides. Exposure to POPs may be a contributor to the greater incidence of poor fetal growth, placental abnormalities, stillbirths, congenital defects and shortened lifespan in the Inuit population compared to non-Aboriginal Canadians. Although maternal exposure to POPs is well established to harm pregnancy outcomes, paternal transmission of the effects of POPs is a possibility that has not been well investigated. We used a rat model to test the hypothesis that exposure to POPs during gestation and suckling leads to developmental defects that are transmitted to subsequent generations via the male lineage. Indeed, developmental exposure to an environmentally relevant Arctic POPs mixture impaired sperm quality and pregnancy outcomes across two subsequent, unexposed generations and altered sperm DNA methylation, some of which are also observed for two additional generations. Genes corresponding to the altered sperm methylome correspond to health problems encountered in the Inuit population. These findings demonstrate that the paternal methylome is sensitive to the environment and that some perturbations persist for at least two subsequent generations. In conclusion, although many factors influence health, paternal exposure to contaminants plays a heretofore-underappreciated role with sperm DNA methylation contributing to the molecular underpinnings involved.
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Affiliation(s)
- Clotilde Maurice
- Research Centre on Reproduction and Intergenerational Health, Department of Animal Sciences, Université Laval, Quebec City, QC G1V 0A6, Canada; (C.M.); (M.D.)
| | - Mathieu Dalvai
- Research Centre on Reproduction and Intergenerational Health, Department of Animal Sciences, Université Laval, Quebec City, QC G1V 0A6, Canada; (C.M.); (M.D.)
| | - Romain Lambrot
- Department of Animal Sciences, McGill University, Ste. Anne de Bellevue, Quebec, QC H9X 3V9, Canada; (R.L.); (S.K.)
- Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada
| | - Astrid Deschênes
- Department of Molecular Medicine, Research Center of CHU of Quebec City, Université Laval, Quebec City, QC G1V 4G, Canada; (A.D.); (M.-P.S.-B.); (A.D.)
| | - Marie-Pier Scott-Boyer
- Department of Molecular Medicine, Research Center of CHU of Quebec City, Université Laval, Quebec City, QC G1V 4G, Canada; (A.D.); (M.-P.S.-B.); (A.D.)
| | - Serge McGraw
- Research Center of CHU Sainte-Justine, Department of Biochemistry and Molecular Medicine, Université de Montral, Montreal, QC H3T 1C5, Canada;
| | - Donovan Chan
- Research Institute of the McGill University Health Centre, Montreal, QC H3Z 2Z3, Canada; (D.C.); (J.T.)
- Departments of Pediatrics, Human Genetics and Pharmacology & Therapeutics, McGill University, Montreal, QC H3Z 2Z3, Canada
| | - Nancy Côté
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC G1V 4G5, Canada;
| | - Ayelet Ziv-Gal
- Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, IL 61802, USA; (A.Z.-G.); (J.A.F.)
| | - Jodi A. Flaws
- Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, IL 61802, USA; (A.Z.-G.); (J.A.F.)
| | - Arnaud Droit
- Department of Molecular Medicine, Research Center of CHU of Quebec City, Université Laval, Quebec City, QC G1V 4G, Canada; (A.D.); (M.-P.S.-B.); (A.D.)
| | - Jacquetta Trasler
- Research Institute of the McGill University Health Centre, Montreal, QC H3Z 2Z3, Canada; (D.C.); (J.T.)
- Departments of Pediatrics, Human Genetics and Pharmacology & Therapeutics, McGill University, Montreal, QC H3Z 2Z3, Canada
| | - Sarah Kimmins
- Department of Animal Sciences, McGill University, Ste. Anne de Bellevue, Quebec, QC H9X 3V9, Canada; (R.L.); (S.K.)
- Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada
| | - Janice L. Bailey
- Research Centre on Reproduction and Intergenerational Health, Department of Animal Sciences, Université Laval, Quebec City, QC G1V 0A6, Canada; (C.M.); (M.D.)
- Correspondence: ; Tel.: +1-418-643-3230
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35
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Lecoutre S, Maqdasy S, Breton C. Maternal obesity as a risk factor for developing diabetes in offspring: An epigenetic point of view. World J Diabetes 2021; 12:366-382. [PMID: 33889285 PMCID: PMC8040079 DOI: 10.4239/wjd.v12.i4.366] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 01/30/2021] [Accepted: 02/19/2021] [Indexed: 02/06/2023] Open
Abstract
According to the developmental origin of health and disease concept, the risk of many age-related diseases is not only determined by genetic and adult lifestyle factors but also by factors acting during early development. In particular, maternal obesity and neonatal accelerated growth predispose offspring to overweight and type 2 diabetes (T2D) in adulthood. This concept mainly relies on the developmental plasticity of adipose tissue and pancreatic β-cell programming in response to suboptimal milieu during the perinatal period. These changes result in unhealthy hypertrophic adipocytes with decreased capacity to store fat, low-grade inflammation and loss of insulin-producing pancreatic β-cells. Over the past years, many efforts have been made to understand how maternal obesity induces long-lasting adipose tissue and pancreatic β-cell dysfunction in offspring and what are the molecular basis of the transgenerational inheritance of T2D. In particular, rodent studies have shed light on the role of epigenetic mechanisms in linking maternal nutritional manipulations to the risk for T2D in adulthood. In this review, we discuss epigenetic adipocyte and β-cell remodeling during development in the progeny of obese mothers and the persistence of these marks as a basis of obesity and T2D predisposition.
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Affiliation(s)
- Simon Lecoutre
- Department of Medicine (H7), Karolinska Institutet, Stockholm 141-86, Sweden
- University of Lille, EA4489, Maternal Malnutrition and Programming of Metabolic Diseases, Lille 59000, France
| | - Salwan Maqdasy
- Department of Medicine (H7), Karolinska Institutet, Stockholm 141-86, Sweden
- Clermont-Ferrand CHU, Department of Endocrinology, Diabetology and Metabolic Diseases, Clermont-Ferrand 63003, France
| | - Christophe Breton
- University of Lille, EA4489, Maternal Malnutrition and Programming of Metabolic Diseases, Lille 59000, France
- U1283-UMR8199-EGID, University of Lille, Institut National de la Santé Et de la Recherche Médicale, Centre National de la Recherche Scientifique, Lille 59000, France
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Zhu L, Marjani SL, Jiang Z. The Epigenetics of Gametes and Early Embryos and Potential Long-Range Consequences in Livestock Species-Filling in the Picture With Epigenomic Analyses. Front Genet 2021; 12:557934. [PMID: 33747031 PMCID: PMC7966815 DOI: 10.3389/fgene.2021.557934] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 02/04/2021] [Indexed: 12/31/2022] Open
Abstract
The epigenome is dynamic and forged by epigenetic mechanisms, such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA species. Increasing lines of evidence support the concept that certain acquired traits are derived from environmental exposure during early embryonic and fetal development, i.e., fetal programming, and can even be "memorized" in the germline as epigenetic information and transmitted to future generations. Advances in technology are now driving the global profiling and precise editing of germline and embryonic epigenomes, thereby improving our understanding of epigenetic regulation and inheritance. These achievements open new avenues for the development of technologies or potential management interventions to counteract adverse conditions or improve performance in livestock species. In this article, we review the epigenetic analyses (DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs) of germ cells and embryos in mammalian livestock species (cattle, sheep, goats, and pigs) and the epigenetic determinants of gamete and embryo viability. We also discuss the effects of parental environmental exposures on the epigenetics of gametes and the early embryo, and evidence for transgenerational inheritance in livestock.
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Affiliation(s)
- Linkai Zhu
- AgCenter, School of Animal Sciences, Louisiana State University, Baton Rouge, LA, United States
| | - Sadie L. Marjani
- Department of Biology, Central Connecticut State University, New Britain, CT, United States
| | - Zongliang Jiang
- AgCenter, School of Animal Sciences, Louisiana State University, Baton Rouge, LA, United States
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tRNA Biology in the Pathogenesis of Diabetes: Role of Genetic and Environmental Factors. Int J Mol Sci 2021; 22:ijms22020496. [PMID: 33419045 PMCID: PMC7825315 DOI: 10.3390/ijms22020496] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/02/2021] [Accepted: 01/03/2021] [Indexed: 02/07/2023] Open
Abstract
The global rise in type 2 diabetes results from a combination of genetic predisposition with environmental assaults that negatively affect insulin action in peripheral tissues and impair pancreatic β-cell function and survival. Nongenetic heritability of metabolic traits may be an important contributor to the diabetes epidemic. Transfer RNAs (tRNAs) are noncoding RNA molecules that play a crucial role in protein synthesis. tRNAs also have noncanonical functions through which they control a variety of biological processes. Genetic and environmental effects on tRNAs have emerged as novel contributors to the pathogenesis of diabetes. Indeed, altered tRNA aminoacylation, modification, and fragmentation are associated with β-cell failure, obesity, and insulin resistance. Moreover, diet-induced tRNA fragments have been linked with intergenerational inheritance of metabolic traits. Here, we provide a comprehensive review of how perturbations in tRNA biology play a role in the pathogenesis of monogenic and type 2 diabetes.
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Dixon G, Matz M. Benchmarking DNA methylation assays in a reef-building coral. Mol Ecol Resour 2020; 21:464-477. [PMID: 33058551 DOI: 10.1111/1755-0998.13282] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 09/17/2020] [Accepted: 10/02/2020] [Indexed: 11/28/2022]
Abstract
Interrogation of chromatin modifications, such as DNA methylation, has the potential to improve forecasting and conservation of marine ecosystems. The standard method for assaying DNA methylation (whole genome bisulphite sequencing), however, is currently too costly to apply at the scales required for ecological research. Here, we evaluate different methods for measuring DNA methylation for ecological epigenetics. We compare whole genome bisulphite sequencing (WGBS) with methylated CpG binding domain sequencing (MBD-seq), and a modified version of MethylRAD we term methylation-dependent restriction site-associated DNA sequencing (mdRAD). We evaluate these three assays in measuring variation in methylation across the genome, between genotypes, and between polyp types in the reef-building coral Acropora millepora. We find that all three assays measure absolute methylation levels similarly for gene bodies (gbM), as well as exons and 1 Kb windows with a minimum Pearson correlation 0.66. Differential gbM estimates were less correlated, but still concurrent across assays. We conclude that MBD-seq and mdRAD are reliable and cost-effective alternatives to WGBS. The considerably lower sequencing effort required for mdRAD to produce comparable methylation estimates makes it particularly useful for ecological epigenetics.
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Affiliation(s)
- Groves Dixon
- Department of Integrative Biology, University of Texas, Austin, TX, USA
| | - Mikhail Matz
- Department of Integrative Biology, University of Texas, Austin, TX, USA
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Fitzgerald E, Hor K, Drake AJ. Maternal influences on fetal brain development: The role of nutrition, infection and stress, and the potential for intergenerational consequences. Early Hum Dev 2020; 150:105190. [PMID: 32948364 PMCID: PMC7481314 DOI: 10.1016/j.earlhumdev.2020.105190] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
An optimal early life environment is crucial for ensuring ideal neurodevelopmental outcomes. Brain development consists of a finely tuned series of spatially and temporally constrained events, which may be affected by exposure to a sub-optimal intra-uterine environment. Evidence suggests brain development may be particularly vulnerable to factors such as maternal nutrition, infection and stress during pregnancy. In this review, we discuss how maternal factors such as these can affect brain development and outcome in offspring, and we also identify evidence which suggests that the outcome can, in many cases, be stratified by socio-economic status (SES), with individuals in lower brackets typically having a worse outcome. We consider the relevant epidemiological evidence and draw parallels to mechanisms suggested by preclinical work where appropriate. We also discuss possible transgenerational effects of these maternal factors and the potential mechanisms involved. We conclude that modifiable factors such as maternal nutrition, infection and stress are important contributors to atypical brain development and that SES also likely has a key role.
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Affiliation(s)
- Eamon Fitzgerald
- University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
| | - Kahyee Hor
- University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
| | - Amanda J Drake
- University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
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Gentile F, Doneddu PE, Riva N, Nobile-Orazio E, Quattrini A. Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration. Int J Mol Sci 2020; 21:E7471. [PMID: 33050475 PMCID: PMC7590163 DOI: 10.3390/ijms21207471] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/05/2020] [Accepted: 10/07/2020] [Indexed: 02/06/2023] Open
Abstract
Increasing evidence gives support for the idea that extra-neuronal factors may affect brain physiology and its predisposition to neurodegenerative diseases. Epidemiological and experimental studies show that nutrition and metabolic disorders such as obesity and type 2 diabetes increase the risk of Alzheimer's and Parkinson's diseases after midlife, while the relationship with amyotrophic lateral sclerosis is uncertain, but suggests a protective effect of features of metabolic syndrome. The microbiota has recently emerged as a novel factor engaging strong interactions with neurons and glia, deeply affecting their function and behavior in these diseases. In particular, recent evidence suggested that gut microbes are involved in the seeding of prion-like proteins and their spreading to the central nervous system. Here, we present a comprehensive review of the impact of metabolism, diet and microbiota in neurodegeneration, by affecting simultaneously several aspects of health regarding energy metabolism, immune system and neuronal function. Advancing technologies may allow researchers in the future to improve investigations in these fields, allowing the buildup of population-based preventive interventions and development of targeted therapeutics to halt progressive neurologic disability.
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Affiliation(s)
- Francesco Gentile
- Experimental Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy; (F.G.); (N.R.)
- Neuromuscular and Neuroimmunology Service, Humanitas Clinical and Research Institute IRCCS, 20089 Milan, Italy; (P.E.D.); (E.N.-O.)
| | - Pietro Emiliano Doneddu
- Neuromuscular and Neuroimmunology Service, Humanitas Clinical and Research Institute IRCCS, 20089 Milan, Italy; (P.E.D.); (E.N.-O.)
| | - Nilo Riva
- Experimental Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy; (F.G.); (N.R.)
- Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Eduardo Nobile-Orazio
- Neuromuscular and Neuroimmunology Service, Humanitas Clinical and Research Institute IRCCS, 20089 Milan, Italy; (P.E.D.); (E.N.-O.)
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy
| | - Angelo Quattrini
- Experimental Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy; (F.G.); (N.R.)
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Marrocco J, Einhorn NR, McEwen BS. Environmental epigenetics of sex differences in the brain. HANDBOOK OF CLINICAL NEUROLOGY 2020; 175:209-220. [PMID: 33008526 DOI: 10.1016/b978-0-444-64123-6.00015-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Experiences throughout the life course lead to unique phenotypes even among those with the same genotype. Genotype sets the substrate on which physiologic processes, which communicate with the brain, mediate the effects of life experiences via epigenetics. Epigenetics modify the expression of genes in the brain and body in response to circulating hormones and other mediators, which are activated to facilitate survival responses through a process called allostasis. Epigenetic signatures can even be inherited, resulting in transgenerational effects. This chapter addresses epigenetics in the context of sex differences, discussing the intersection between genetics and gonadal hormones and their effect in the brain at discrete developmental periods.
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Affiliation(s)
- Jordan Marrocco
- Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, NY, United States.
| | - Nathan R Einhorn
- Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, NY, United States
| | - Bruce S McEwen
- Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, NY, United States
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Senaldi L, Smith-Raska M. Evidence for germline non-genetic inheritance of human phenotypes and diseases. Clin Epigenetics 2020; 12:136. [PMID: 32917273 PMCID: PMC7488552 DOI: 10.1186/s13148-020-00929-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 08/26/2020] [Indexed: 12/20/2022] Open
Abstract
It is becoming increasingly apparent that certain phenotypes are inherited across generations independent of the information contained in the DNA sequence, by factors in germ cells that remain largely uncharacterized. As evidence for germline non-genetic inheritance of phenotypes and diseases continues to grow in model organisms, there are fewer reports of this phenomenon in humans, due to a variety of complications in evaluating this mechanism of inheritance in humans. This review summarizes the evidence for germline-based non-genetic inheritance in humans, as well as the significant challenges and important caveats that must be considered when evaluating this process in human populations. Most reports of this process evaluate the association of a lifetime exposure in ancestors with changes in DNA methylation or small RNA expression in germ cells, as well as the association between ancestral experiences and the inheritance of a phenotype in descendants, down to great-grandchildren in some cases. Collectively, these studies provide evidence that phenotypes can be inherited in a DNA-independent manner; the extent to which this process contributes to disease development, as well as the cellular and molecular regulation of this process, remain largely undefined.
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Affiliation(s)
- Liana Senaldi
- Division of Newborn Medicine, Department of Pediatrics, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
| | - Matthew Smith-Raska
- Division of Newborn Medicine, Department of Pediatrics, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA. .,Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, USA.
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Ben Maamar M, Beck D, Nilsson E, McCarrey JR, Skinner MK. Developmental origins of transgenerational sperm histone retention following ancestral exposures. Dev Biol 2020; 465:31-45. [PMID: 32628935 PMCID: PMC7484192 DOI: 10.1016/j.ydbio.2020.06.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 06/16/2020] [Accepted: 06/19/2020] [Indexed: 12/16/2022]
Abstract
Numerous environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. Alterations in the germline epigenome are necessary to transmit transgenerational phenotypes. In previous studies, the pesticide DDT (dichlorodiphenyltrichloroethane) and the agricultural fungicide vinclozolin were shown to promote the transgenerational inheritance of sperm differential DNA methylation regions, non-coding RNAs and histone retention, which are termed epimutations. These epimutations are able to mediate this epigenetic inheritance of disease and phenotypic variation. The current study was designed to investigate the developmental origins of the transgenerational differential histone retention sites (called DHRs) during gametogenesis of the sperm. Vinclozolin and DDT were independently used to promote the epigenetic transgenerational inheritance of these DHRs. Male control lineage, DDT lineage and vinclozolin lineage F3 generation rats were used to isolate round spermatids, caput epididymal spermatozoa, and caudal sperm. The DHRs distinguishing the control versus DDT lineage or vinclozolin lineage samples were determined at these three developmental stages. DHRs and a reproducible core of histone H3 retention sites were observed using an H3 chromatin immunoprecipitation-sequencing (ChIP-Seq) analysis in each of the germ cell populations. The chromosomal locations and genomic features of the DHRs were analyzed. A cascade of epigenetic histone retention site alterations was found to be initiated in the round spermatids and then further modified during epididymal sperm maturation. Observations show that in addition to alterations in sperm DNA methylation and ncRNA expression previously identified, the induction of differential histone retention sites (DHRs) in the later stages of spermatogenesis also occurs. This novel component of epigenetic programming during spermatogenesis can be environmentally altered and transmitted to subsequent generations through epigenetic transgenerational inheritance.
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Affiliation(s)
- Millissia Ben Maamar
- Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA
| | - Daniel Beck
- Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA
| | - Eric Nilsson
- Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA
| | - John R McCarrey
- Department of Biology, University of Texas at San Antonio, San Antonio, TX, 78249, USA
| | - Michael K Skinner
- Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA.
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da Cruz RS, Chen E, Smith M, Bates J, de Assis S. Diet and Transgenerational Epigenetic Inheritance of Breast Cancer: The Role of the Paternal Germline. Front Nutr 2020; 7:93. [PMID: 32760734 PMCID: PMC7373741 DOI: 10.3389/fnut.2020.00093] [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: 04/06/2020] [Accepted: 05/21/2020] [Indexed: 12/13/2022] Open
Abstract
The past decade has made evident that in addition to passing their genetic material at conception, parents also transmit a molecular memory of past environmental experiences, including nutritional status, to their progeny through epigenetic mechanisms. In the 1990s, it was proposed that breast cancer originates in utero. Since then, an overwhelming number of studies in human cohorts and animal models have provided support for that hypothesis. It is becoming clear, however, that exposure in the parent generation can lead to multigenerational and transgenerational inheritance of breast cancer. Importantly, recent data from our lab and others show that pre-conception paternal diets reprogram the male germline and modulate breast cancer development in offspring. This review explores the emerging evidence for transgenerational epigenetic inheritance of breast cancer focusing on studies associated with ancestral nutritional factors or related markers such as birth weight. We also explore paternal factors and the epigenetic mechanisms of inheritance through the male germline while also reviewing the existing literature on maternal exposures in pregnancy and its effects on subsequent generations. Finally, we discuss the importance of this mode of inheritance in the context of breast cancer prevention, the challenges, and outstanding research questions in the field.
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Affiliation(s)
- Raquel Santana da Cruz
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, United States
| | - Elaine Chen
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, United States
| | - Megan Smith
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, United States
| | - Jaedus Bates
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, United States
| | - Sonia de Assis
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, United States
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45
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Schellong K, Melchior K, Ziska T, Rancourt RC, Henrich W, Plagemann A. Maternal but Not Paternal High-Fat Diet (HFD) Exposure at Conception Predisposes for 'Diabesity' in Offspring Generations. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E4229. [PMID: 32545776 PMCID: PMC7345576 DOI: 10.3390/ijerph17124229] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 06/09/2020] [Accepted: 06/10/2020] [Indexed: 01/02/2023]
Abstract
While environmental epigenetics mainly focuses on xenobiotic endocrine disruptors, dietary composition might be one of the most important environmental exposures for epigenetic modifications, perhaps even for offspring generations. We performed a large-scale rat study on key phenotypic consequences from parental (F0) high-caloric, high-fat diet (HFD) food intake, precisely and specifically at mating/conception, focusing on 'diabesity' risk in first- (F1) and second- (F2) generation offspring of both sexes. F0 rats (maternal or paternal, respectively) received HFD overfeeding, starting six weeks prior to mating with normally fed control rats. The maternal side F1 offspring of both sexes developed a 'diabesity' predisposition throughout life (obesity, hyperleptinemia, hyperglycemia, insulin resistance), while no respective alterations occurred in the paternal side F1 offspring, neither in males nor in females. Mating the maternal side F1 females with control males under standard feeding conditions led, again, to a 'diabesity' predisposition in the F2 generation, which, however, was less pronounced than in the F1 generation. Our observations speak in favor of the critical impact of maternal but not paternal metabolism around the time frame of reproduction for offspring metabolic health over generations. Such fundamental phenotypic observations should be carefully considered in front of detailed molecular epigenetic approaches on eventual mechanisms.
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Affiliation(s)
- Karen Schellong
- Division of ‘Experimental Obstetrics’, Clinic of Obstetrics, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, 13353 Berlin, Germany; (K.S.); (K.M.); (T.Z.); (R.C.R.)
| | - Kerstin Melchior
- Division of ‘Experimental Obstetrics’, Clinic of Obstetrics, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, 13353 Berlin, Germany; (K.S.); (K.M.); (T.Z.); (R.C.R.)
| | - Thomas Ziska
- Division of ‘Experimental Obstetrics’, Clinic of Obstetrics, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, 13353 Berlin, Germany; (K.S.); (K.M.); (T.Z.); (R.C.R.)
| | - Rebecca C. Rancourt
- Division of ‘Experimental Obstetrics’, Clinic of Obstetrics, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, 13353 Berlin, Germany; (K.S.); (K.M.); (T.Z.); (R.C.R.)
| | - Wolfgang Henrich
- Clinic of Obstetrics, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, 13353 Berlin, Germany;
| | - Andreas Plagemann
- Division of ‘Experimental Obstetrics’, Clinic of Obstetrics, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, 13353 Berlin, Germany; (K.S.); (K.M.); (T.Z.); (R.C.R.)
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Lecoutre S, Kwok KHM, Petrus P, Lambert M, Breton C. Epigenetic Programming of Adipose Tissue in the Progeny of Obese Dams. Curr Genomics 2020; 20:428-437. [PMID: 32477000 PMCID: PMC7235387 DOI: 10.2174/1389202920666191118092852] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 10/08/2019] [Accepted: 10/21/2019] [Indexed: 01/13/2023] Open
Abstract
According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and the resulting accelerated growth in neonates predispose offspring to obesity and associated metabolic diseases that may persist across generations. In this context, the adipose tissue has emerged as an important player due to its involvement in metabolic health, and its high potential for plasticity and adaptation to environmental cues. Recent years have seen a growing interest in how maternal obesity induces long-lasting adipose tissue remodeling in offspring and how these modifications could be transmitted to subsequent generations in an inter- or transgenerational manner. In particular, epigenetic mechanisms are thought to be key players in the developmental programming of adipose tissue, which may partially mediate parts of the transgenerational inheritance of obesity. This review presents data supporting the role of maternal obesity in the developmental programming of adipose tissue through epigenetic mechanisms. Inter- and transgenerational effects on adipose tissue expansion are also discussed in this review.
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Affiliation(s)
- Simon Lecoutre
- University of Lille, EA4489, Equipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F-59000 Lille, France.,Department of Medicine (H7), Karolinska Institutet, 141 86 Stockholm, Sweden
| | - Kelvin H M Kwok
- Department of Biosciences and Nutrition, Karolinska Insitutet, 141 86 Stockholm, Sweden
| | - Paul Petrus
- Department of Medicine (H7), Karolinska Institutet, 141 86 Stockholm, Sweden
| | - Mélanie Lambert
- Department of Medicine (H7), Karolinska Institutet, 141 86 Stockholm, Sweden
| | - Christophe Breton
- University of Lille, EA4489, Equipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F-59000 Lille, France
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Pei Y, Forstmeier W, Kempenaers B. Offspring performance is well buffered against stress experienced by ancestors. Evolution 2020; 74:1525-1539. [PMID: 32463119 DOI: 10.1111/evo.14026] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 05/14/2020] [Accepted: 05/17/2020] [Indexed: 11/27/2022]
Abstract
Evolution should render individuals resistant to stress and particularly to stress experienced by ancestors. However, many studies report negative effects of stress experienced by one generation on the performance of subsequent generations. To assess the strength of such transgenerational effects we propose a strategy aimed at overcoming the problem of type I errors when testing multiple proxies of stress in multiple ancestors against multiple offspring performance traits, and we apply it to a large observational dataset on captive zebra finches (Taeniopygia guttata). We combine clear one-tailed hypotheses with steps of validation, meta-analytic summary of mean effect sizes, and independent confirmatory testing. We find that drastic differences in early growth conditions (nestling body mass 8 days after hatching varied sevenfold between 1.7 and 12.4 g) had only moderate direct effects on adult morphology (95% confidence interval [CI]: r = 0.19-0.27) and small direct effects on adult fitness traits (r = 0.02-0.12). In contrast, we found no indirect effects of parental or grandparental condition (r = -0.017 to 0.002; meta-analytic summary of 138 effect sizes), and mixed evidence for small benefits of matching environments between parents and offspring, as the latter was not robust to confirmatory testing in independent datasets. This study shows that evolution has led to a remarkable robustness of zebra finches against undernourishment. Our study suggests that transgenerational effects are absent in this species, because CIs exclude all biologically relevant effect sizes.
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Affiliation(s)
- Yifan Pei
- Department of Behavioural Ecology and Evolutionary Genetics, Max Planck Institute for Ornithology, Seewiesen, 82319, Germany
| | - Wolfgang Forstmeier
- Department of Behavioural Ecology and Evolutionary Genetics, Max Planck Institute for Ornithology, Seewiesen, 82319, Germany
| | - Bart Kempenaers
- Department of Behavioural Ecology and Evolutionary Genetics, Max Planck Institute for Ornithology, Seewiesen, 82319, Germany
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Risk of eating disorders in international adoptees: a cohort study using Swedish national population registers. Epidemiol Psychiatr Sci 2020; 29:e131. [PMID: 32452335 PMCID: PMC7264708 DOI: 10.1017/s2045796020000451] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
AIMS Compared to the general population, adoptees are more often referred to specialist psychiatric treatment, exhibit increased risk of suicide and display more symptoms of attention-deficit/hyperactivity-disorder. However, little is known about the impact of being an adoptee on the risk of developing an eating disorder. The aim of the present study was to assess whether international adoptees have a higher risk for eating disorders than native Swedes. METHODS In the present retrospective cohort study, data from the Swedish total population registers on individuals born between 1979 and 2005 were used to assess whether international adoptees residing in Sweden (n = 25 287) have a higher risk for anorexia nervosa (AN) and other eating disorders (OED) than non-adoptees with Swedish-born parents from the general population (n = 2 046 835). The patterns of these results were compared to those for major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and anxiety disorders to determine whether any observed effects were unique to eating disorders or reflected a more general impact on mental health outcomes. RESULTS A survival analysis adjusting for relevant demographic covariates revealed an elevated risk of all examined psychiatric disorders in international adoptees: hazard ratios (95% confidence intervals) are 1.21 (1.04-1.41) for AN, 1.60 (1.44-1.79) for OED, 1.90 (1.81-2.00) for MDD, 1.25 (1.09-1.44) for OCD, and 1.69 (1.60-1.78) for anxiety disorders. CONCLUSIONS Elevated risk of eating disorders as well as of MDD, OCD, and anxiety disorders was found in international adoptees. A parallel pattern between AN and OCD was observed, which both display less elevated rates than the other diagnoses. A considerable number of biological, environmental, and societal factors have been suggested to explain the observed differences in mental health between adoptees and non-adoptees, but they remain primarily theoretical.
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Franzago M, Santurbano D, Vitacolonna E, Stuppia L. Genes and Diet in the Prevention of Chronic Diseases in Future Generations. Int J Mol Sci 2020; 21:ijms21072633. [PMID: 32290086 PMCID: PMC7178197 DOI: 10.3390/ijms21072633] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 03/30/2020] [Accepted: 04/08/2020] [Indexed: 12/21/2022] Open
Abstract
Nutrition is a modifiable key factor that is able to interact with both the genome and epigenome to influence human health and fertility. In particular, specific genetic variants can influence the response to dietary components and nutrient requirements, and conversely, the diet itself is able to modulate gene expression. In this context and the era of precision medicine, nutrigenetic and nutrigenomic studies offer significant opportunities to improve the prevention of metabolic disturbances, such as Type 2 diabetes, gestational diabetes, hypertension, and cardiovascular diseases, even with transgenerational effects. The present review takes into account the interactions between diet, genes and human health, and provides an overview of the role of nutrigenetics, nutrigenomics and epigenetics in the prevention of non-communicable diseases. Moreover, we focus our attention on the mechanism of intergenerational or transgenerational transmission of the susceptibility to metabolic disturbances, and underline that the reversibility of epigenetic modifications through dietary intervention could counteract perturbations induced by lifestyle and environmental factors.
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Affiliation(s)
- Marica Franzago
- Department of Medicine and Aging, School of Medicine and Health Sciences, ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy
| | | | - Ester Vitacolonna
- Department of Medicine and Aging, School of Medicine and Health Sciences, ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy
- Correspondence:
| | - Liborio Stuppia
- Center for Advanced Studies and Technology (CAST), ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy
- Department of Psychological, Health and Territorial Sciences, School of Medicine and Health Sciences, ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy
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