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Menezes ACF, Wunderlich ALM, Luiz KG, Frigoli GF, Costa IRD, Stopa LRDS, Souza CF, Guergolette RP, Shishido PK, Aquino ABO, Forcato S, Gerardin DCC, Zaia CTBV, Uchoa ET, Fernandes GSA. Neonatal undernutrition induced by litter size expansion alters testicular parameters in adult Wistar rats. Br J Nutr 2024; 132:862-873. [PMID: 39391932 DOI: 10.1017/s0007114524002149] [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] [Indexed: 10/12/2024]
Abstract
Several models of maternal undernutrition reveal impairment of testicular development and compromise spermatogenesis in male offspring. The expansion of the litter size model, valuable for studying the impact of undernutrition on early development, has not yet been used to evaluate the consequences of early undernutrition in the adult male reproductive system. For this purpose, pups were raised in either normal litter (ten pups/dam) or large litter (LL; sixteen pups/dam). On postnatal day 90, sexual behaviour was evaluated or blood, adipose and reproductive tissues were collected for biochemical, histological and morphological analysis. Adult LL animals were lighter and thinner than controls. They showed increased food intake, but decrease of retroperitoneal white adipose tissue weight, glycaemia after oral glucose overload and plasma concentration of cholesterol. Reproductive organ weights were not altered by undernutrition, but histopathological analysis revealed an increased number of abnormal seminiferous tubules and number of immature spermatids in the tubular lumen of LL animals. These animals also showed reduction in total spermatic reserve and daily sperm production in the testes. Undernutrition decreased the number of Sertoli cells, and testosterone production was increased in the LL group. Mitochondrial activity of spermatozoa remained unchanged between experimental groups, suggesting no significant impact on the energy-related processes associated with sperm function. All animals from both experimental groups were considered sexually competent, with no significant difference in the parameters of sexual behaviour. We conclude that neonatal undernutrition induces histological and physiological testicular changes, without altering sperm quality and sexual behaviour of animals.
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Affiliation(s)
- Ana Camila Ferreira Menezes
- State University of Londrina, Biological Sciences Centre, Department of General Biology, Laboratory of Toxicology and Metabolic Disorders of Reproduction, Londrina, Brazil
| | | | - Karen Gomes Luiz
- State University of Londrina, Biological Sciences Centre, Department of General Biology, Laboratory of Toxicology and Metabolic Disorders of Reproduction, Londrina, Brazil
| | - Giovanna Fachetti Frigoli
- State University of Londrina, Biological Sciences Centre, Department of General Biology, Laboratory of Toxicology and Metabolic Disorders of Reproduction, Londrina, Brazil
| | - Ivana Regina D Costa
- State University of Londrina, Biological Sciences Centre, Department of General Biology, Laboratory of Toxicology and Metabolic Disorders of Reproduction, Londrina, Brazil
| | | | - Camila Franciele Souza
- Multicentre Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
| | | | - Polyana Keiko Shishido
- Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
| | | | - Simone Forcato
- Multicentre Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
| | - Daniela Cristina Ceccatto Gerardin
- Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
- Multicentre Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
- Department of Physiological Sciences, State University of Londrina, Londrina, Brazil
| | - Cássia Thaïs Bussamra Vieira Zaia
- Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
- Multicentre Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
- Department of Physiological Sciences, State University of Londrina, Londrina, Brazil
| | - Ernane Torres Uchoa
- Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
- Multicentre Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
- Department of Physiological Sciences, State University of Londrina, Londrina, Brazil
| | - Glaura Scantamburlo Alves Fernandes
- State University of Londrina, Biological Sciences Centre, Department of General Biology, Laboratory of Toxicology and Metabolic Disorders of Reproduction, Londrina, Brazil
- Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil
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Ghasemi Z, Alizadeh Mogadam Masouleh A, Rashki Ghaleno L, Akbarinejad V, Rezazadeh Valojerdi M, Shahverdi A. Maternal nutrition and fetal imprinting of the male progeny. Anim Reprod Sci 2024; 265:107470. [PMID: 38657462 DOI: 10.1016/j.anireprosci.2024.107470] [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: 12/28/2023] [Revised: 03/28/2024] [Accepted: 03/30/2024] [Indexed: 04/26/2024]
Abstract
The global population as well as the demand for human food is rapidly growing worldwide, which necessitates improvement of efficiency in livestock operations. In this context, environmental factors during fetal and/or neonatal life have been observed to influence normal physical and physiological function of an individual during adulthood, and this phenomenon is called fetal or developmental programming. While numerous studies have reported the impact of maternal factors on development of the female progeny, limited information is available on the potential effects of fetal programming on reproductive function of the male offspring. Therefore, the objective for this review article was to focus on available literature regarding the impact of maternal factors, particularly maternal nutrition, on reproductive system of the male offspring. To this end, we highlighted developmental programming of the male offspring in domestic species (i.e., pig, cow and sheep) as well as laboratory species (i.e., mice and rat) during pregnancy and lactation. In this sense, we pointed out the effects of maternal nutrition on various functions of the male offspring including hypothalamic-pituitary axis, hormonal levels, testicular tissue and semen parameters.
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Affiliation(s)
- Zahrasadat Ghasemi
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Animal Core Facility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - AliReza Alizadeh Mogadam Masouleh
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Gyn-medicum, Center for Reproductive Medicine, Göttingen, Germany; Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany.
| | - Leila Rashki Ghaleno
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Vahid Akbarinejad
- Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Mojtaba Rezazadeh Valojerdi
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Abdolhossein Shahverdi
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
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3
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de Oliveira JS, Silva AADN, Dias FCR, de Oliveira EL, de Oliveira Filho EF, Soares PC, Ferreira CMDO, da Silva Junior VA. Histomorphometric and oxidative evaluation of the offspring's testis from type 2 diabetic female rats treated with metformin and pentoxifylline. Int J Exp Pathol 2022; 103:174-189. [PMID: 35734873 PMCID: PMC9482357 DOI: 10.1111/iep.12446] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/08/2022] [Accepted: 04/09/2022] [Indexed: 11/27/2022] Open
Abstract
Type 2 diabetes mellitus (T2D) during pregnancy is characterized by high levels of reactive oxygen species and pro-inflammatory factors in the placenta. Once these reactive species reach the foetus, they trigger physiological adaptations that allow the foetus to survive, but programme the organism to develop metabolic disorders in adulthood. The male reproductive system is highly susceptible to foetal programming. This study aimed to investigate the effects of intrauterine exposure to T2D on testicular histomorphometry and redox homeostasis of adult rats and evaluate the effects of maternal treatment with metformin and pentoxifylline. Female rats were induced to T2D, then treated with metformin and pentoxifylline, or co-treated with both drugs. The females were mated, the male offspring were sacrificed on postnatal day 90, and the testicles were collected for analysis. Metformin protected the tubular compartment, with the maintenance of the Sertoli cell population and daily sperm production. Pentoxifylline attenuated the effects of diabetes on Leydig cells, in addition to stimulating testosterone production and lowering lipid peroxidation. Intrauterine exposure to T2D results in important testicular alterations that compromise gonadal function, and the co-treatment with metformin and pentoxifylline may represent a promising therapy that attenuates these effects by combining the positive influences in both the tubular and interstitial compartments of the testicular parenchyma.
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Affiliation(s)
| | | | | | | | | | - Pierre Castro Soares
- Department of Veterinary MedicineFederal Rural University of PernambucoRecifePernambucoBrazil
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Bertasso IM, de Moura EG, Pietrobon CB, Cabral SS, Kluck GEG, Atella GC, Manhães AC, Lisboa PC. Low protein diet during lactation programs hepatic metabolism in adult male and female rats. J Nutr Biochem 2022; 108:109096. [PMID: 35779796 DOI: 10.1016/j.jnutbio.2022.109096] [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: 07/03/2021] [Revised: 02/28/2022] [Accepted: 06/08/2022] [Indexed: 10/17/2022]
Abstract
The liver is an essential regulator of energy metabolism, and its function can be disrupted by nutritional alterations. Since liver development continues during breastfeeding nutritional challenges during this period predispose patients to diseases throughout life. A maternal protein-restricted (PR) diet during lactation promotes reductions in the body weight, adiposity, and plasma glucose and insulin, leptin resistance and an increase in corticosterone and catecholamines in adult male rat offspring. Here, we investigated hepatic metabolism in the offspring (both sexes) of PR (8% protein diet during lactation) and control (23% protein diet) dams. Both male and female offspring were evaluated at 6 months of age. PR males had no liver steatosis and manifested a reduction in lipids in hepatocytes adjacent to the vasculature. These animals had lower levels of esterified cholesterol in hepatocytes, suggesting higher biliary excretion, unchanged glycolysis and gluconeogenesis, and lower contents of the markers of mitochondrial redox balance and endoplasmic reticulum (ER) stress response and estrogen receptor alpha. PR females showed normal hepatic morphology associated with higher uptake of cholesterol esters, normal glycolysis and gluconeogenesis, and lower ER stress parameters without changes in the key markers of the redox balance. Additionally, these animals had lower content of estrogen receptor alpha and higher content of androgen receptor. The maternal PR diet during lactation did not program hepatic lipid accumulation in the adult progeny. However, several repair homeostasis pathways were altered in males and females, possibly compromising maintenance of normal liver function.
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Affiliation(s)
- Iala Milene Bertasso
- Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Egberto Gaspar de Moura
- Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carla Bruna Pietrobon
- Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Suelen Silva Cabral
- Laboratory of Lipids and Lipoprotein Biochemistry, Biochemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - George Eduardo Gabriel Kluck
- Laboratory of Lipids and Lipoprotein Biochemistry, Biochemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Georgia Correa Atella
- Laboratory of Lipids and Lipoprotein Biochemistry, Biochemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Alex Christian Manhães
- Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Patrícia Cristina Lisboa
- Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
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5
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Vipin VA, Blesson CS, Yallampalli C. Maternal low protein diet and fetal programming of lean type 2 diabetes. World J Diabetes 2022; 13:185-202. [PMID: 35432755 PMCID: PMC8984567 DOI: 10.4239/wjd.v13.i3.185] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 12/30/2021] [Accepted: 02/10/2022] [Indexed: 02/06/2023] Open
Abstract
Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood. Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy, and impaired nutrition has been an immense issue across the globe. In recent years, type 2 diabetes (T2D) has reached epidemic proportion and is a severe public health problem in many countries. Although plenty of research has already been conducted to tackle T2D which is associated with obesity, little is known regarding the etiology and pathophysiology of lean T2D, a variant of T2D. Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D, although other mechanisms might also contribute to the pathology. Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype. In addition, clear sex-specific disease prevalence was observed in different studies. Consequently, more research is essential for the understanding of the etiology and pathophysiology of lean T2D, which might help to develop better disease prevention and treatment strategies. This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.
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Affiliation(s)
- Vidyadharan Alukkal Vipin
- Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States
| | - Chellakkan Selvanesan Blesson
- Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States
- Family Fertility Center, Texas Children's Hospital, Houston, TX 77030, United States
| | - Chandra Yallampalli
- Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States
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Muranishi Y, Parry L, Vachette-Dit-Martin M, Saez F, Coudy-Gandilhon C, Sauvanet P, Volle DH, Tournayre J, Bottari S, Carpentiero F, Martinez G, Muroňová J, Escoffier J, Bruhat A, Maurin AC, Averous J, Arnoult C, Fafournoux P, Jousse C. When idiopathic male infertility is rooted in maternal malnutrition during the perinatal period in mice. Biol Reprod 2021; 106:463-476. [PMID: 34875016 DOI: 10.1093/biolre/ioab222] [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: 07/22/2021] [Revised: 11/18/2021] [Accepted: 12/02/2021] [Indexed: 11/14/2022] Open
Abstract
Infertility represents a growing burden worldwide, with one in seven couples presenting difficulties conceiving. Amongst these, 10-15% of the men have idiopathic infertility that does not correlate with any defect in the classical sperm parameters measured. In the present study, we used a mouse model to investigate the effects of maternal undernutrition on fertility in male progeny. Our results indicate that mothers fed on a low protein diet during gestation and lactation produce male offspring with normal sperm morphology, concentration and motility but exhibiting an overall decrease of fertility when they reach adulthood. Particularly, in contrast to control, sperm from these offspring show a remarkable lower capacity to fertilize oocytes when copulation occurs early in the estrus cycle relative to ovulation, due to an altered sperm capacitation. Our data demonstrate for the first time that maternal nutritional stress can have long-term consequences on the reproductive health of male progeny by affecting sperm physiology, especially capacitation, with no observable impact on spermatogenesis and classical quantitative and qualitative sperm parameters. Moreover, our experimental model could be of major interest to study, explain, and ultimately treat certain categories of infertilities.
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Affiliation(s)
- Yuki Muranishi
- Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, UMR1019, F-63000 Clermont-Ferrand, France.,Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan
| | - Laurent Parry
- Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, UMR1019, F-63000 Clermont-Ferrand, France
| | | | - Fabrice Saez
- GReD Institute, Université Clermont Auvergne, Inserm, CNRS, Clermont-Ferrand, France
| | - Cécile Coudy-Gandilhon
- Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, UMR1019, F-63000 Clermont-Ferrand, France
| | - Pierre Sauvanet
- UMR 1071 Inserm/Université Clermont Auvergne; USC-INRA 2018, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Clermont-Ferrand, France.,Service de chirurgie et hépatobiliaire, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - David H Volle
- Inserm U1103, CNRS UMR6293-Université Clermont Auvergne, Institute Genetic, Reproduction and Development, Team "Environment, Metabolism, Spermatogenesis and Pathophysiology & Inheritance", Clermont-Ferrand, France
| | - Jérémy Tournayre
- Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, UMR1019, F-63000 Clermont-Ferrand, France
| | | | - Francesca Carpentiero
- Université Grenoble Alpes, Grenoble, France.,Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, Grenoble, France
| | - Guillaume Martinez
- Université Grenoble Alpes, Grenoble, France.,Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, Grenoble, France.,Hôpital Couple-Enfant, Centre Hospitalier Universitaire de Grenoble, UM de Génétique Chromosomique, Grenoble, France
| | - Jana Muroňová
- Université Grenoble Alpes, Grenoble, France.,Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, Grenoble, France
| | - Jessica Escoffier
- Université Grenoble Alpes, Grenoble, France.,Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, Grenoble, France
| | - Alain Bruhat
- Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, UMR1019, F-63000 Clermont-Ferrand, France
| | - Anne-Catherine Maurin
- Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, UMR1019, F-63000 Clermont-Ferrand, France
| | - Julien Averous
- Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, UMR1019, F-63000 Clermont-Ferrand, France
| | - Christophe Arnoult
- Université Grenoble Alpes, Grenoble, France.,Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, Grenoble, France
| | - Pierre Fafournoux
- Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, UMR1019, F-63000 Clermont-Ferrand, France
| | - Céline Jousse
- Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, UMR1019, F-63000 Clermont-Ferrand, France
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7
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Fesser EA, Gianatiempo O, Berardino BG, Alberca CD, Urrutia L, Falasco G, Sonzogni SV, Chertoff M, Cánepa ET. Impaired social cognition caused by perinatal protein malnutrition evokes neurodevelopmental disorder symptoms and is intergenerationally transmitted. Exp Neurol 2021; 347:113911. [PMID: 34767796 DOI: 10.1016/j.expneurol.2021.113911] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 10/05/2021] [Accepted: 11/01/2021] [Indexed: 12/26/2022]
Abstract
Nutritional inadequacy before birth and during postnatal life can seriously interfere with brain development and lead to persistent deficits in learning and behavior. In this work, we asked if protein malnutrition affects domains of social cognition and if these phenotypes can be transmitted to the next generation. Female mice were fed with a normal or hypoproteic diet during pregnancy and lactation. After weaning, offspring were fed with a standard chow. Social interaction, social recognition memory, and dominance were evaluated in both sexes of F1 offspring and in the subsequent F2 generation. Glucose metabolism in the whole brain was analyzed through preclinical positron emission tomography. Genome-wide transcriptional analysis was performed in the medial prefrontal cortex followed by gene-ontology enrichment analysis. Compared with control animals, malnourished mice exhibited a deficit in social motivation and recognition memory and displayed a dominant phenotype. These altered behaviors, except for dominance, were transmitted to the next generation. Positron emission tomography analysis revealed lower glucose metabolism in the medial prefrontal cortex of F1 malnourished offspring. This brain region showed genome-wide transcriptional dysregulation, including 21 transcripts that overlapped with autism-associated genes. Our study cannot exclude that the lower maternal care provided by mothers exposed to a low-protein diet caused an additional impact on social cognition. Our results showed that maternal protein malnutrition dysregulates gene expression in the medial prefrontal cortex, promoting altered offspring behavior that was intergenerationally transmitted. These results support the hypothesis that early nutritional deficiency represents a risk factor for the emergence of symptoms associated with neurodevelopmental disorders.
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Affiliation(s)
- Estefanía A Fesser
- Grupo Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Ciudad de Buenos Aires, Argentina
| | - Octavio Gianatiempo
- Grupo Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Ciudad de Buenos Aires, Argentina
| | - Bruno G Berardino
- Grupo Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Ciudad de Buenos Aires, Argentina
| | - Carolina D Alberca
- Grupo Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Ciudad de Buenos Aires, Argentina
| | - Leandro Urrutia
- Centro de Imágenes Moleculares, Fleni, Escobar, Buenos Aires, Argentina
| | - Germán Falasco
- Centro de Imágenes Moleculares, Fleni, Escobar, Buenos Aires, Argentina
| | - Silvina V Sonzogni
- Grupo Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Ciudad de Buenos Aires, Argentina
| | - Mariela Chertoff
- Grupo Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Ciudad de Buenos Aires, Argentina
| | - Eduardo T Cánepa
- Grupo Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Ciudad de Buenos Aires, Argentina.
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8
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Zambrano E, Nathanielsz PW, Rodríguez-González GL. Developmental programming and ageing of male reproductive function. Eur J Clin Invest 2021; 51:e13637. [PMID: 34107063 DOI: 10.1111/eci.13637] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/25/2021] [Accepted: 06/08/2021] [Indexed: 12/22/2022]
Abstract
Developmental programming predisposes offspring to metabolic, behavioural and reproductive dysfunction in adult life. Evidence is accumulating that ageing phenotype and longevity are in part developmentally programmed in each individual. Unfortunately, there are few studies addressing the effects of developmental programming by maternal nutrition on the rate of ageing of the male reproductive system. This review will discuss effects of foetal exposure to maternal environmental challenges on male offspring fertility and normal ageing of the male reproductive system. We focus on several key factors involved in reproductive ageing such as decreased hormone production, DNA fragmentation, oxidative stress, telomere shortening, epigenetics, maternal lifestyle and nutrition. There is compelling evidence that ageing of the male reproductive system is developmentally programmed. Both maternal over- or undernutrition accelerate ageing of male offspring reproductive function through similar mechanisms such as decreased serum testosterone levels, increase in oxidative stress biomarkers in both the testes and sperm and changes in sperm quality. Importantly, even in adult life, exercise in male offspring of obese mothers improves adverse effects of programming on reproductive function. Maternal consumption of a low-protein diet causes transgenerational effects in progeny via the paternal line. The seminal fluid has effects on the intrauterine environment. Programming by male factors may involve more than just the sperm. Improving knowledge on developmental programming ageing interactions will improve not only male health and life span but also the health of future generations by reducing programming via the paternal line.
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Affiliation(s)
- Elena Zambrano
- Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, México
| | | | - Guadalupe L Rodríguez-González
- Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, México
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9
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Ajuogu PK, Al-Aqbi MAK, Hart RA, McFarlane JR, Smart NA. A low protein maternal diet during gestation has negative effects on male fertility markers in rats - A Systematic Review and Meta-analysis. J Anim Physiol Anim Nutr (Berl) 2020; 105:157-166. [PMID: 32654274 DOI: 10.1111/jpn.13411] [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: 08/29/2019] [Revised: 02/20/2020] [Accepted: 04/08/2020] [Indexed: 12/11/2022]
Abstract
Research indicates that some adult diseases including reproductive pathologies are programmed in utero during foetal development. In particular, maternal low dietary protein, during the most critical developmental periods of male foetal development, may have a detrimental impact on male fertility through direct and epigenetic mechanisms. The aim of our study was to evaluate the impact of a gestational low protein diet on fertility markers in male offspring in rats through a systematic review and meta-analysis. A systematic search using PubMed, and EMBASE databases was performed and two investigators independently screened the 1,703 prospective articles. Eleven articles met the eligibility criteria. Outcome measures were pooled using random-effects models and expressed as mean differences (MDs) at 95% CIs for each study. The results reveal significant reduction in testis weight (MD (mean difference) -0.08 g; -0.12, -0.42; p = .0001), epididymal sperm count (MD -35.34 × 106 cells; -52.15, -18.53; p = .0001), number of Sertoli cells (MD -7.27 × 106 (-13.92, -0.62; p = .03), testosterone (T) concentration (MD -0.29 ng/ml; -0.48, -0.09; p = .004) and luteinising hormone (LH) concentration (MD of -0.24 ng/ml; -0.45, 0.04; p = .02) in comparison with controls. In contrast, follicle-stimulating hormone (FSH) concentration (MD of 0.07 ng/ml; -0.16, 0.29; p = .56) was not significantly different from controls. We conclude that low gestational dietary protein maternal intake potentially negatively impacts fertility in male progeny later in life. The mechanisms of action responsible for these phenomena remain unclear.
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Affiliation(s)
- Peter K Ajuogu
- School of Science and Technology, University of New England, Armidale, NSW, Australia
| | - Mohammed A K Al-Aqbi
- School of Science and Technology, University of New England, Armidale, NSW, Australia.,College of Agriculture, Wasit University, Wasit, Iraq
| | - Robert A Hart
- School of Science and Technology, University of New England, Armidale, NSW, Australia
| | - James R McFarlane
- Centre for Bioactive Discovery in Heath and Ageing, University of New England, Armidale, NSW, Australia
| | - Neil A Smart
- School of Science and Technology, University of New England, Armidale, NSW, Australia
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10
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Ajuogu PK, Al-Aqbi MA, Hart RA, Wolden M, Smart NA, McFarlane JR. The effect of dietary protein intake on factors associated with male infertility: A systematic literature review and meta-analysis of animal clinical trials in rats. Nutr Health 2020; 26:53-64. [PMID: 31992124 DOI: 10.1177/0260106019900731] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Studies have shown that the amount of protein in the diet affects the hypothalamic-pituitary-testis axis and sub-optimal quantity reduces male fertility potential in both animals and humans. However, individual research reports on the factors associated with male infertility are collectively uncharacterized. AIM We systematically reviewed, and meta-analysed animal (rats) studies on the effect of low protein diet on factors associated with male infertility. METHODS PubMed Central, EMBASE and Scopus databases were searched from inception to 30 March 2019 for the study concepts and related keywords in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Data on the outcome measures were extracted and pooled across trials using random-effects model and expressed as mean differences (MD) at a 95% confidence interval (CI). RESULTS Twelve trials identified from 3327 studies, met our inclusion criteria in the comparison of a low protein diet (2-10% protein) vs control protein diet (17-23% protein). The results showed that a low protein diet caused a significant reduction in the body weight (P = 0.0001) testis weight (P = 0.0001), seminal vesicle weight (P = 0.0003), epididymis weight P = 0.02), serum testosterone (P = 0.001) and follicle-stimulating hormone (FSH) concentrations (P = 0.04) compared with the control treatments. No effect on luteinizing hormone (LH) plasma concentration (P = 0.13) was observed. CONCLUSION This study revealed that low protein diet caused significant reductions in body weight, testis, epididymis and seminal vesicle weights, serum testosterone and FSH concentration in rats. We infer that sub-optimal protein consumption reduces the gonadal and endocrine function, and consequently male infertility.
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Affiliation(s)
| | - Mohammed Ak Al-Aqbi
- School of Science and Technology, University of New England, Australia.,College of Agriculture, Wasit University, Iraq
| | - Robert A Hart
- School of Science and Technology, University of New England, Australia
| | | | - Neil A Smart
- School of Science and Technology, University of New England, Australia
| | - James R McFarlane
- School of Science and Technology, University of New England, Australia
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11
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Louvandini H, Corrêa PS, Amorín R, Liu L, Ieda EH, Jimenez CR, Tsai SM, McManus CM, Peñagaricano F. Gestational and lactational exposure to gossypol alters the testis transcriptome. BMC Genomics 2020; 21:59. [PMID: 31952482 PMCID: PMC6969474 DOI: 10.1186/s12864-020-6487-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 01/13/2020] [Indexed: 11/10/2022] Open
Abstract
Background Reproductive capacity can be altered by challenges experienced during critical periods of development, including fetal development and early neonatal life. Gossypol is a polyphenolic compound, commonly found in cotton seeds, that impairs male reproduction. Here, we investigated whether the exposure to gossypol in utero and during lactation alters male reproductive function in sheep. From conception until 60 days postpartum, ewes were randomly assigned to a control diet or a gossypol-rich diet based on cottonseed. Lamb testicles were removed at 60 days of age and subjected to RNA-sequencing. Results Lambs derived from the maternal cottonseed diet showed significantly lower growth and lower testis weight as a proportion of the total body weight, and reduced testosterone levels. In addition, the testis transcriptome was significantly altered by the maternal cottonseed diet. Most of the altered genes are directly implicated in testis development and sperm biology, cell communication, iron ion metabolism, calcium homeostasis and signaling, among other functions. Interestingly, network analysis revealed that exposure to gossypol significantly disturbed coexpression patterns among spermatogenesis-related genes, suggesting a disruption in coregulation mechanisms. Conclusions Our findings provide evidence that maternal exposure to gossypol alters male reproductive function in the offspring, with potential lasting or lifelong negative consequences.
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Affiliation(s)
- Helder Louvandini
- Department of Animal Sciences, University of Florida, Gainesville, FL, 32611, USA.,Laboratory of Animal Nutrition, Centre for Nuclear Energy in Agriculture, University of São Paulo, Piracicaba, SP, 13400-970, Brazil
| | - Patricia S Corrêa
- Department of Animal Sciences, University of Florida, Gainesville, FL, 32611, USA.,Laboratory of Animal Nutrition, Centre for Nuclear Energy in Agriculture, University of São Paulo, Piracicaba, SP, 13400-970, Brazil.,Laboratory of Molecular and Cell Biology, Centre for Nuclear Energy in Agriculture, University of São Paulo, Piracicaba, SP, 13400-970, Brazil
| | - Rocío Amorín
- Department of Animal Sciences, University of Florida, Gainesville, FL, 32611, USA
| | - Lihe Liu
- Department of Animal Sciences, University of Florida, Gainesville, FL, 32611, USA
| | - Egon H Ieda
- Laboratory of Animal Nutrition, Centre for Nuclear Energy in Agriculture, University of São Paulo, Piracicaba, SP, 13400-970, Brazil
| | - Carolina R Jimenez
- Laboratory of Animal Nutrition, Centre for Nuclear Energy in Agriculture, University of São Paulo, Piracicaba, SP, 13400-970, Brazil
| | - Siu M Tsai
- Laboratory of Molecular and Cell Biology, Centre for Nuclear Energy in Agriculture, University of São Paulo, Piracicaba, SP, 13400-970, Brazil
| | - Concepta M McManus
- Institute of Biology, University of Brasília, Brasília, Federal District, 70910-900, Brazil
| | - Francisco Peñagaricano
- Department of Animal Sciences, University of Florida, Gainesville, FL, 32611, USA. .,University of Florida Genetics Institute, University of Florida, Gainesville, FL, 32611, USA.
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12
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Lin Y, Li L, Li Y, Wang K, Wei D, Xu S, Feng B, Che L, Fang Z, Li J, Zhuo Y, Wu D. Interpretation of Fiber Supplementation on Offspring Testicular Development in a Pregnant Sow Model from a Proteomics Perspective. Int J Mol Sci 2019; 20:ijms20184549. [PMID: 31540305 PMCID: PMC6770271 DOI: 10.3390/ijms20184549] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 09/06/2019] [Accepted: 09/10/2019] [Indexed: 12/13/2022] Open
Abstract
To study the effects of maternal fiber supplementation during pregnancy on the testicular development of male offspring and its possible mechanisms, 36 sows (Landrace × Yorkshire) were allocated to either a control diet (n = 18) or a fiber diet (the control diet supplemented with 22.60 g/kg inulin and 181.60 g/kg cellulosic; n = 18) during pregnancy. The body and testes weight of the offspring, 7-day-old piglets, was recorded. Testes were collected for further analyses. Results showed that the testicular organ index and the number of spermatogonia in single seminiferous tubule were higher in piglets from the fiber group than from the control group (p < 0.05). In addition, a significant increase in the concentration of glucose, lactate, and lipids in the testes was found in the fiber group (p < 0.05). Proteomic analysis suggested that there were notable differences in glucolipid transport and metabolism, oxidation, and male reproduction-related proteins expression between the two groups (p < 0.05). Results revealed that the most enriched signaling pathways in the fiber group testes included starch and sucrose metabolism, fatty acid metabolism, glutathione metabolism, and the renin-angiotensin system. mRNA expression analyzes further confirmed the importance of some signaling pathways in maternal fiber nutrition regulating offspring testicular development. Our results shed new light on the underlying molecular mechanisms of maternal fiber nutrition on offspring testicular development and provided a valuable insight for future explorations of the effect of maternal fiber nutrition on man reproduction.
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Affiliation(s)
- Yan Lin
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
- Correspondence: (Y.L.); (D.W.)
| | - Lujie Li
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - Yang Li
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - Ke Wang
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - Dongqin Wei
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - Shengyu Xu
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - Bin Feng
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - Lianqiang Che
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - Zhengfeng Fang
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - Jian Li
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - Yong Zhuo
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
| | - De Wu
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed Science, Ministry of Agriculture, Sichuan Agricultural University, Chengdu 611130, China; (L.L.); (Y.L.); (S.X.); (B.F.); (Y.Z.)
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Wenjiang 611130, China
- Correspondence: (Y.L.); (D.W.)
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13
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LESZCZYNSKI ERICC, VISKER JOSEPHR, FERGUSON DAVIDP. The Effect of Growth Restriction on Voluntary Physical Activity Engagement in Mice. Med Sci Sports Exerc 2019; 51:2201-2209. [DOI: 10.1249/mss.0000000000002040] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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14
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Genovese P, Herrera E, Riaño V, Bielli A. “Subnutrition effects during pregnancy and lactation on mitosis, apoptosis and androgen receptor expression in the rat testis”. Reprod Domest Anim 2018; 54:506-513. [DOI: 10.1111/rda.13385] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 11/18/2018] [Indexed: 01/25/2023]
Affiliation(s)
- Patricia Genovese
- Veterinary Faculty, Department of Morphology and Development, Area of Histology and Embryology University of Uruguay Montevideo Uruguay
| | - Emiliano Herrera
- Veterinary Faculty, Department of Morphology and Development, Area of Histology and Embryology University of Uruguay Montevideo Uruguay
| | - Victoria Riaño
- Veterinary Faculty, Department of Morphology and Development, Area of Histology and Embryology University of Uruguay Montevideo Uruguay
| | - Alejandro Bielli
- Veterinary Faculty, Department of Morphology and Development, Area of Histology and Embryology University of Uruguay Montevideo Uruguay
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15
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Izvolskaia MS, Sharova VS, Ignatiuk VM, Voronova SN, Zakharova LA. Abolition of prenatal lipopolysaccharide-induced reproductive disorders in rat male offspring by fulvestrant. Andrologia 2018; 51:e13204. [DOI: 10.1111/and.13204] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 10/18/2018] [Accepted: 10/29/2018] [Indexed: 01/16/2023] Open
Affiliation(s)
- Marina S. Izvolskaia
- Koltsov Institute of Developmental Biology; Russian Academy of Sciences; Moscow Russia
| | - Victoria S. Sharova
- Koltsov Institute of Developmental Biology; Russian Academy of Sciences; Moscow Russia
| | | | - Svetlana N. Voronova
- Koltsov Institute of Developmental Biology; Russian Academy of Sciences; Moscow Russia
| | - Liudmila A. Zakharova
- Koltsov Institute of Developmental Biology; Russian Academy of Sciences; Moscow Russia
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16
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Santos SAA, Camargo AC, Constantino FB, Colombelli KT, Mani F, Rinaldi JC, Franco S, Portela LMF, Duran BOS, Scarano WR, Hinton BT, Felisbino SL, Justulin LA. Maternal Low-Protein Diet Impairs Prostate Growth in Young Rat Offspring and Induces Prostate Carcinogenesis With Aging. J Gerontol A Biol Sci Med Sci 2018; 74:751-759. [DOI: 10.1093/gerona/gly118] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Indexed: 01/02/2023] Open
Affiliation(s)
- Sergio A A Santos
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | - Ana C Camargo
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | | | - Ketlin T Colombelli
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | - Fernanda Mani
- Department of Chemistry and Biochemistry, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | - Jaqueline C Rinaldi
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | - Suelen Franco
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | - Luiz M F Portela
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | - Bruno O S Duran
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | - Wellerson R Scarano
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | - Barry T Hinton
- Department of Cell Biology, University of Virginia Health System, Charlottesville
| | - Sergio L Felisbino
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
| | - Luis A Justulin
- Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil
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17
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Abstract
Well-controlled intrauterine development is an essential condition for many aspects of normal adult physiology and health. This process is disrupted by poor maternal nutrition status during pregnancy. Indeed, physiological adaptations occur in the fetus to ensure nutrient supply to the most vital organs at the expense of the others, leading to irreversible consequences in tissue formation and differentiation. Evidence indicates that maternal undernutrition in early life promotes changes in key hormones, such as glucocorticoids, growth hormones, insulin-like growth factors, estrogens and androgens, during fetal development. These alterations can directly or indirectly affect hormone release, hormone receptor expression/distribution, cellular function or tissue organization, and impair tissue growth, differentiation and maturation to exert profound long-term effects on the offspring. Within the male reproductive system, maternal protein malnutrition alters development, structure, and function of the gonads, testes and prostate gland. Consequently, these changes impair the reproductive capacity of the male offspring. Further, permanent alterations in the prostate gland occur at the molecular and cellular level and thereby affect the onset of late life diseases such as prostatitis, hyperplasia and even prostate cancer. This review assembles current thoughts on the concepts and mechanisms behind the developmental origins of health and disease as they relate to protein malnutrition, and highlights the effects of maternal protein malnutrition on rat prostate development and homeostasis. Such insights on developmental trajectories of adult-onset prostate disease may help provide a foundation for future studies in this field.
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18
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Zito JB, Hanna A, Kadoo N, Tomaszycki ML. Early life stress increases testosterone and corticosterone and alters stress physiology in zebra finches. Horm Behav 2017; 95:57-64. [PMID: 28782547 DOI: 10.1016/j.yhbeh.2017.08.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 07/31/2017] [Accepted: 08/02/2017] [Indexed: 01/16/2023]
Abstract
Early life stress has enduring effects on behavior and physiology. However, the effects on hormones and stress physiology remain poorly understood. In the present study, parents of zebra finches of both sexes were exposed to an increased foraging paradigm from 3 to 33days post hatching. Plasma and brains were collected from chicks at 3 developmental time points: post hatching days 25, 60 and adulthood. Plasma was assayed for testosterone (T), estradiol (E2), and corticosterone (CORT). The paraventricular nucleus of the hypothalamus was assessed for corticotrophin releasing factor (CRH) and glucocorticoid receptor (GR) expression. As expected, body mass was lower in nutritionally stressed animals compared to controls at multiple ages. Nutritionally stressed animals overall had higher levels of CORT than did control and this was particularly apparent in females at post hatching day 25. Nutritionally stressed animals also had a higher number of cells expressing CRH and GR in the paraventricular nucleus of the hypothalamus than did controls. There was an interaction, such that both measures were higher in control animals at PHD 25, but higher in NS animals by adulthood. Females, regardless of treatment, had higher circulating CORT and a higher number of cells expressing CRH than did males. Nutritionally stressed animals also had higher levels of T than did control animals, and this difference was greatest for males at post hatching day 60. There were no effects of nutritional stress on E2. These findings suggest that nutritional stress during development has long-lasting effects on testosterone and stress physiology.
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Affiliation(s)
- J Bayley Zito
- Department of Psychology, Wayne State University, Detroit, MI 48202, USA
| | - Angy Hanna
- Department of Psychology, Wayne State University, Detroit, MI 48202, USA
| | - Nora Kadoo
- Department of Psychology, Wayne State University, Detroit, MI 48202, USA
| | - Michelle L Tomaszycki
- Department of Psychology, Program in Neuroscience, Lafayette College, Easton, PA 18042, USA.
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19
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OLIVEIRA JSD, SILVA AADN, SOUZA SLD, MORAIS RND, NEVES de MELO E, MAIA FCL, SILVA JUNIOR VAD. Histomorphometric evaluation of the testicular parenchyma of rats submittedto protein restriction during intrauterine and postnatal life. Turk J Biol 2017. [DOI: 10.3906/biy-1610-20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
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20
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Pillay N, Rimbach R, Rymer T. Pre- and postnatal dietary protein deficiency influences anxiety, memory and social behaviour in the African striped mouse Rhabdomys dilectus chakae. Physiol Behav 2016; 161:38-46. [PMID: 27080079 DOI: 10.1016/j.physbeh.2016.04.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Revised: 03/23/2016] [Accepted: 04/08/2016] [Indexed: 12/21/2022]
Abstract
Dietary protein deficiency influences the behavioural phenotypes of mammals. We studied whether protein deficiency during gestation and/or post-weaning heightened anxiety, reduced memory recall and influenced competitive ability in the African striped mouse Rhabdomys dilectus chakae. Mice were subjected to five protein diet treatments, which they received continuously, or were raised on one diet to weaning and switched to an alternate diet post-weaning (Day 16): 1) HP-HP: high protein (24%); first letter pair indicates maternal diet and the second pair indicates offspring diet post-weaning; 2) BP-BP: baseline protein (19%); 3) LP-LP: low protein (10%); 4) HP-LP: switched from high to low protein diet; and 5) LP-HP: switched from low protein to high protein diet. From Day 70, when mice were sexually mature, 20 individuals (10 males, 10 females) per treatment were subjected to three successive experiments, in which we tested their anxiety responses in: 1) an open field arena (time spent in the centre of the open field); 2) novel object recognition (time spent exploring a novel object); and 3) social interactions (excluding BP-BP) in age-matched same-sex dyadic encounters (aggressive, amicable and avoidance behaviours). LP-LP and LP-HP treatment mice spent the least amount of time in the centre of the open field, did not demonstrate object preference compared to the other treatments, and were the most aggressive in dyadic encounters. Our study shows that the systemic effects of protein-deficient diets during early life shapes the behavioural phenotype in R. d. chakae, possibly through early organisation of neuro-biological pathways or competition among littermates.
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Affiliation(s)
- Neville Pillay
- School of Animal, Plant & Environmental Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Rebecca Rimbach
- School of Animal, Plant & Environmental Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Tasmin Rymer
- School of Animal, Plant & Environmental Sciences, University of the Witwatersrand, Johannesburg, South Africa; College of Marine and Environmental Sciences, James Cook University, P. O. Box 6811, Cairns, Queensland 4870, Australia; Centre for Tropical Environmental and Sustainability Sciences, James Cook University, P. O. Box 6811, Cairns, Queensland 4870, Australia.
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21
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Izvolskaia MS, Tillet Y, Sharova VS, Voronova SN, Zakharova LA. Disruptions in the hypothalamic-pituitary-gonadal axis in rat offspring following prenatal maternal exposure to lipopolysaccharide. Stress 2016; 19:198-205. [PMID: 26941006 DOI: 10.3109/10253890.2016.1149695] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Postnatal treatment with bacterial endotoxin lipopolysaccharide (LPS) changes the activity of the hypothalamic-pituitary-gonadal (HPG) axis and the gonadotropin-releasing hormone (GnRH) surge in rats. Exposure to an immune challenge in the critical periods of development has profound and long-lasting effects on the stress response, immune, metabolic, and reproductive functions. Prenatal LPS treatment delays the migration of GnRH neurons associated with increased cytokine release in maternal and fetal compartments. We investigated the effects of a single maternal exposure to LPS (18 μg/kg, i.p.) on day 12 (embryonic day (E)12) of pregnancy on reproductive parameters in rat offspring. Hypothalamic GnRH content, plasma luteinizing hormone (LH), testosterone, and estradiol concentrations were measured in both male and female offsprings at different stages of postnatal development by RIA and ELISA (n = 10 each per group). Body weight and in females day of vaginal opening (VO) were recorded. In offspring exposed to LPS prenatally, compared with controls, body weight was decreased in both sexes at P5 and P30; in females, VO was delayed; hypothalamic GnRH content was decreased at postnatal days 30-60 (P30-P60) in both sexes; plasma LH concentration was decreased at P14-P60 in females; plasma concentrations of testosterone/estradiol were increased at P14 in females, and plasma estradiol was increased at P14 in males. Hence activation of the maternal immune system by LPS treatment at a prenatal critical period leads to decreased GnRH and LH levels in pre- and postpubertal life and sex steroid imbalance in the prepubertal period, and delayed sexual maturation of female offspring.
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Affiliation(s)
- Marina S Izvolskaia
- a Koltsov Institute of Developmental Biology, Russian Academy of Sciences , Moscow , Russia and
| | - Yves Tillet
- b UMR 7247 INRA CNRS, Physiologie de la Reproduction et des Comportements, Universite de Tours PRC INRA , Nouzilly , France
| | - Viktoria S Sharova
- a Koltsov Institute of Developmental Biology, Russian Academy of Sciences , Moscow , Russia and
| | - Svetlana N Voronova
- a Koltsov Institute of Developmental Biology, Russian Academy of Sciences , Moscow , Russia and
| | - Lyudmila A Zakharova
- a Koltsov Institute of Developmental Biology, Russian Academy of Sciences , Moscow , Russia and
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22
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Maternal protein restriction in pregnancy and/or lactation affects seminiferous tubule organization in male rat offspring. J Dev Orig Health Dis 2015; 3:321-6. [PMID: 25102260 DOI: 10.1017/s2040174412000360] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Maternal protein restriction (MPR) during pregnancy impaired the reproduction of male offspring. We investigated, during the first wave of spermatogenesis, whether MPR exerts deleterious effects on germ cell proliferation and differentiation, as well as androgen receptor (AR) protein expression, which was used as a marker for Sertoli cell (SC) maturation. At the beginning of pregnancy (day 0), dams were fed a control diet (C: 20% casein) or a restricted isocaloric diet (R: 10% casein). After birth, four groups were established: CC, RR, CR and RC (first letter diet during pregnancy and second during lactation). Male offspring were studied at postnatal days 14, 21 and 36. At birth, pup body weight was unchanged. Body weight and testis weight were reduced in RR and CR groups at all ages evaluated. MPR delayed the germinal epithelium development at all ages evaluated. On performing Western blot and immunohistochemistry, AR expression was found to be lower in the three restricted groups. The results suggest that MPR during pregnancy and/or lactation delays SC maturation and germ cell differentiation, and affects intratubular organization. These changes might be responsible for the lower fertility rate at older ages.
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23
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Pereyra-Venegas J, Segura-Alegría B, Guadarrama-Olmos JC, Mariscal-Tovar S, Quiróz-González S, Jiménez-Estrada I. Effects provoked by chronic undernourishment on the fibre type composition and contractility of fast muscles in male and female developing rats. J Anim Physiol Anim Nutr (Berl) 2014; 99:974-86. [DOI: 10.1111/jpn.12274] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 10/27/2014] [Indexed: 11/26/2022]
Affiliation(s)
- J. Pereyra-Venegas
- Departamento de Biología; Facultad de Estudios Superiores Iztacala; Universidad Nacional Autónoma de México; Tlalnepantla de Baz Estado de México México
- Instituto de Fisiología Celular; Universidad Nacional Autónoma de México; México City México
| | - B. Segura-Alegría
- Departamento de Biología; Facultad de Estudios Superiores Iztacala; Universidad Nacional Autónoma de México; Tlalnepantla de Baz Estado de México México
| | - J. C. Guadarrama-Olmos
- Departamento de Fisiología, Biofísica y Neurociencias; Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional; San Pedro Zacatenco; Del. Gustavo A. Madero. México City México
| | - S. Mariscal-Tovar
- Departamento de Fisiología, Biofísica y Neurociencias; Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional; San Pedro Zacatenco; Del. Gustavo A. Madero. México City México
| | - S. Quiróz-González
- Departamento de Acupuntura y Rehabilitación; Universidad Estatal del Valle de Ecatepec; Valle de Anáhuac Ecatepec Estado de México México
| | - I. Jiménez-Estrada
- Departamento de Fisiología, Biofísica y Neurociencias; Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional; San Pedro Zacatenco; Del. Gustavo A. Madero. México City México
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Sui S, He B, Jia Y, Li R, Cai D, Li X, Song H, Jia L, Zhao R. Maternal protein restriction during gestation and lactation programs offspring ovarian steroidogenesis and folliculogenesis in the prepubertal gilts. J Steroid Biochem Mol Biol 2014; 143:267-76. [PMID: 24787658 DOI: 10.1016/j.jsbmb.2014.04.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Revised: 04/17/2014] [Accepted: 04/20/2014] [Indexed: 01/28/2023]
Abstract
Maternal malnutrition may disrupt ovarian functions in adult offspring. Steroidogenesis and folliculogenesis in the offspring ovary appear to be the major targets of nutritional programming. Nevertheless, the mechanism by which maternal low-protein diet affects the offspring steroidogenesis and folliculogenesis, and the possible pathway linking these two processes remain unclear. In this study, Landrace×Yorkshire crossbred sows were fed either standard (SP) or low-protein (LP, 50% of the SP) diets throughout gestation and lactation. Female offspring were fed the same diet after weaning until 6 months of age. LP offspring had higher serum 17β-estradiol level (P<0.01), which was accompanied by lower mRNA (P<0.05) but higher protein (P<0.05) expression of cytochrome P450 aromatase (CYP19A1) in the ovary. CYP19A1 protein up-regulation was associated with lower ovarian expression of drosha (P<0.05) and miRNAs targeting CYP19A1 (P<0.05). LP offspring had less graafian follicles with more apoptotic granulosa cells (P<0.05), as well as higher caspase 3 activity (P<0.05) and FasL expression (P<0.05) in the ovary. FasL gene up-regulation was associated with higher ERα protein expression (P<0.05) and binding to FasL gene promoter. These results suggest that a maternal LP diet in pregnancy and lactation elevated serum 17β-estradiol level by activating CYP19A1 through miRNA-mediated mechanism, and induced granulosa apoptosis in graafian follicles through ER-activated Fas/FasL-caspase 3 pathway.
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Affiliation(s)
- Shiyan Sui
- Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Bin He
- Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Yimin Jia
- Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Runsheng Li
- Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Demin Cai
- Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Xi Li
- Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Haogang Song
- Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Longfei Jia
- Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Ruqian Zhao
- Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
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Zambrano E, Guzmán C, Rodríguez-González GL, Durand-Carbajal M, Nathanielsz PW. Fetal programming of sexual development and reproductive function. Mol Cell Endocrinol 2014; 382:538-549. [PMID: 24045010 DOI: 10.1016/j.mce.2013.09.008] [Citation(s) in RCA: 94] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Revised: 09/03/2013] [Accepted: 09/05/2013] [Indexed: 11/15/2022]
Abstract
The recent growth of interest in developmental programming of physiological systems has generally focused on the cardiovascular system (especially hypertension) and predisposition to metabolic dysfunction (mainly obesity and diabetes). However, it is now clear that the full range of altered offspring phenotypes includes impaired reproductive function. In rats, sheep and nonhuman primates, reproductive capacity is altered by challenges experienced during critical periods of development. This review will examine available experimental evidence across commonly studied experimental species for developmental programming of female and male reproductive function throughout an individual's life-course. It is necessary to consider events that occur during fetal development, early neonatal life and prior to and during puberty, during active reproductive life and aging as reproductive performance declines.
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Affiliation(s)
- Elena Zambrano
- Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México.
| | - Carolina Guzmán
- HIPAM, Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM)/Hospital General de México, México
| | - Guadalupe L Rodríguez-González
- Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México
| | - Marta Durand-Carbajal
- Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México
| | - Peter W Nathanielsz
- Center for Pregnancy and Newborn Research, Department of Obstetrics, University of Texas Health Sciences Center San Antonio, TX, United States
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Zhang Y, Piao Y, Li Y, Song M, Tang P, Li C. 4-Nitrophenol induces Leydig cells hyperplasia, which may contribute to the differential modulation of the androgen receptor and estrogen receptor-α and -β expression in male rat testes. Toxicol Lett 2013; 223:228-35. [DOI: 10.1016/j.toxlet.2013.09.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2013] [Revised: 09/15/2013] [Accepted: 09/16/2013] [Indexed: 10/26/2022]
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Toledo FC, Perobelli JE, Pedrosa FPC, Anselmo-Franci JA, Kempinas WDG. In utero protein restriction causes growth delay and alters sperm parameters in adult male rats. Reprod Biol Endocrinol 2011; 9:94. [PMID: 21702915 PMCID: PMC3141647 DOI: 10.1186/1477-7827-9-94] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2010] [Accepted: 06/24/2011] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Recent studies have supported the concept of "fetal programming" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study. METHODS Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t-test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05. RESULTS We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC. CONCLUSIONS In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood.
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Affiliation(s)
- Fabíola C Toledo
- Graduate Program in Cell and Structural Biology, Institute of Biology, University of Campinas - UNICAMP, Campinas, SP, Brazil
- Department of Morphology, Institute of Biosciences, UNESP - Universidade Estadual Paulista, Botucatu, SP, Brazil
| | - Juliana E Perobelli
- Graduate Program in Cell and Structural Biology, Institute of Biology, University of Campinas - UNICAMP, Campinas, SP, Brazil
- Department of Morphology, Institute of Biosciences, UNESP - Universidade Estadual Paulista, Botucatu, SP, Brazil
| | - Flávia PC Pedrosa
- Department of Morphology, Institute of Biosciences, UNESP - Universidade Estadual Paulista, Botucatu, SP, Brazil
| | - Janete A Anselmo-Franci
- Department of Morphology, Stomatology and Physiology, School of Dentistry, University of São Paulo - USP, Ribeirão Preto, SP, Brazil
| | - Wilma DG Kempinas
- Department of Morphology, Institute of Biosciences, UNESP - Universidade Estadual Paulista, Botucatu, SP, Brazil
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Ramos CDF, Lima SS, Rocha MLM, Lotufo BM, Sampaio FJB, Barradas PC, Tenório F. Maternal malnutrition during lactation alters gonadotropin-releasing hormone expression in the hypothalamus of weaned male rat pups. Nutr Neurosci 2010; 13:170-4. [PMID: 20670472 DOI: 10.1179/147683010x12611460764327] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Gonadotropin-releasing hormone (GnRH) is the key hormone regulating reproduction. Its feedback regulation is exercised by estradiol. The early postnatal period is critical for sexual differentiation. Despite the fact that malnutrition-related reproductive suppression in rats is a well-documented phenomenon, we had no knowledge, until now, on how maternal malnutrition affects GnRH expression and estradiol serum concentrations of weaned pups. Six pregnant Wistar rats were separated into three groups at delivery with 6 pups each: control group (C) with free access to a standard diet containing 23% protein; protein energy restricted group (PER) with free access to an isoenergy and 8% protein diet; and an energy-restricted (ER) group receiving a standard diet in restricted quantities, which were calculated according to the mean ingestion of the PER group. At 21 days post partum, the animals were killed and the serum estradiol was evaluated by radioimmunoassay. Immunohistochemistry for GNRH was performed. The serum estradiol concentration was decreased in PER and ER groups compared with C (PER, 34%; ER, 19%;P < 0.01) and the staining of GNRH was restricted to arcuate nucleus and median eminence in the control group while in PER and ER stained processes aligned with the third ventricle wall (periventricular nucleus) were present. In conclusion, our data reinforce the concept that the maternal nutritional state during lactation is critical for sexual maturation since maternal malnutrition resulted in a neuron migration delay evidenced by an altered GnRH expression profile, probably a consequence of low estradiol serum levels.
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Affiliation(s)
- Cristiane da Fonte Ramos
- Departamento de Anatomia, Unidade de Pesquisa Urogenital, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brasil.
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Harding JE, Derraik JG, Bloomfield FH. Maternal undernutrition and endocrine development. Expert Rev Endocrinol Metab 2010; 5:297-312. [PMID: 30764054 DOI: 10.1586/eem.09.62] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Maternal undernutrition, whether it occurs before conception, throughout gestation or during lactation, may lead to physiological adaptations in the fetus that will affect the health of the offspring in adult life. The timing, severity, duration and nature of the maternal nutritional insult may affect the offspring differently. Other factors determining outcome following maternal undernutrition are fetal number and gender. Importantly, effects of maternal undernutrition may be carried over into subsequent generations. This review examines the endocrine pathways disrupted by maternal undernutrition that affect the long-term postnatal health of the offspring. Maternal and childhood undernutrition are highly prevalent in low- and middle-income countries, and, in developed countries, unintentional undernutrition may arise from maternal dieting. It is, therefore, important that we better understand the mechanisms driving the long-term effects of maternal undernutrition, as well as identifying treatments to ameliorate the associated mortality and morbidity.
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Affiliation(s)
- Jane E Harding
- a Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
| | - José Gb Derraik
- b Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
| | - Frank H Bloomfield
- c Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
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Bittencourt Brasil F, Silva Faria T, Barcellos Sampaio FJ, da Fonte Ramos C. The effect of maternal malnutrition during lactation on the endometrial ERalpha expression, collagen type, and blood vessels in the rats offspring at puberty. Anat Rec (Hoboken) 2010; 293:162-70. [PMID: 19899115 DOI: 10.1002/ar.21028] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The aim of this manuscript was to evaluate the effects of maternal protein-energy-restriction and energy restriction during lactation on endometrial collagen and blood vessels, uterus Eralpha expression, and estradiol serum levels in the rats offspring at puberty. At parturition, dams were grouped as: control group (C), with free access to standard rat chow containing 23% protein and 17,038.7 KJ/Kg; protein-energy restricted group (PER), with free access to formulated chow containing 8% protein but made isoenergetic to the C diet (17,038.7 KJ/Kg); and energy-restricted group (ER), which received standard rat chow containing 23% protein based on the mean ingestion of the PER group corresponding to 60% of that consumed by the control group. After weaning, all female pups had free access to standard laboratory chow until puberty, when they were killed at the diestrum stage. The uterine ERalpha expression was determined by Western-Blot and estradiol serum levels by radioimmunoassay. Endometrial collagen and blood vessels were quantified by stereology. The volumetric density of blood vessels (C = 70.7 +/- 2.2; PER = 29.2 +/- 2.4; ER = 32.3 +/- 3.6; P < 0.001) and endometrial collagen (C = 31.1 +/- 1; PER = 26.9 +/- 1.0; ER = 26.5 +/- 0.7; P < 0.05) were significantly reduced in both malnourished groups. The ER group presented higher estradiol serum levels (C = 69.2 +/- 6.4; PER = 73.4 +/- 5.5; ER = 101.0 +/- 5.4; P < 0.01) in relation to C and PER groups. ERalpha expression was greater in both malnourished groups (C = 0.11 +/- 0.02; PER = 0.41 +/- 0.12; ER = 0.35 +/- 0.03; P < 0.05). In conclusion, maternal malnutrition during lactation caused changes in endometrial angiogenesis, collagen deposition, and Eralpha expression in female offspring that will appear in puberty and could affect the reproductive biology of the female offspring.
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da Silva Faria T, de Bittencourt Brasil F, Sampaio FJB, da Fonte Ramos C. Maternal malnutrition during lactation affects folliculogenesis, gonadotropins, and leptin receptors in adult rats. Nutrition 2009; 26:1000-7. [PMID: 20018485 DOI: 10.1016/j.nut.2009.09.026] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2009] [Revised: 09/08/2009] [Accepted: 09/28/2009] [Indexed: 11/15/2022]
Abstract
OBJECTIVE The goal of this study was to evaluate if maternal malnutrition during lactation could possibly program folliculogenesis, the ovarian expression of gonadotropins, leptin, and their receptors. METHODS At parturition, dams were randomly assigned to a control group (C), with free access to a standard laboratory diet containing 23% protein, and a protein-energy-restricted group (PER), with free access to an iso-energy and protein-restricted diet containing 8% protein. After weaning, all female pups had free access to the standard laboratory diet until 90 d of age when they were euthanized in the diestrum stage. RESULTS Maternal malnutrition caused decreases in the number of primordial (C 6.60 ± 0.24, PER 5.20 ± 0.20, P = 0.01), primary (C 5.80 ± 0.66, PER 4.00 ± 0.31, P = 0.04), and Graafian (C 2.18 ± 0.29, PER 1.08 ± 0.37, P = 0.05) follicle numbers. Maternal malnutrition led to a significant decrease in the aromatase mRNA expression (C 0.536 ± 0.008, PER 0.353 ± 0.041, P = 0.01) follicle-stimulating hormone receptor (C 1.25 ± 0.17, PER 0.75 ± 0.02, P = 0.04), luteinizing hormone receptor (C 0.93 ± 0.09, PER 0.54 ± 0.10, P = 0.03), leptin (C 0.55 ± 0.03, PER 0.42 ± 0.03, P = 0.04), Ob-R (C 1.05 ± 0.12, PER 0.64 ± 0.07, P = 0.03), and Ob-Rb (C 1.34 ± 0.21, PER 0.47 ± 0.10, P = 0.02) transcripts when compared with C. CONCLUSION Maternal malnutrition during lactation modulates folliculogenesis and the expression of the different isoforms of leptin and gonadotropin receptors and the aromatase enzyme. This probably is a consequence of alterations in perinatal leptin concentrations that may play a crucial role in determining the occurrence of long-term metabolic changes.
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Ferreira RV, Gombar FM, da Silva Faria T, Costa WS, Sampaio FJB, da Fonte Ramos C. Metabolic programming of ovarian angiogenesis and folliculogenesis by maternal malnutrition during lactation. Fertil Steril 2009; 93:2572-80. [PMID: 19591993 DOI: 10.1016/j.fertnstert.2009.05.050] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2009] [Revised: 04/20/2009] [Accepted: 05/07/2009] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To evaluate whether maternal malnutrition during lactation programs ovarian folliculogenesis and the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and its receptors KDR, Flt-1, and FGFR. DESIGN Experimental study. SETTING University-based research laboratory. ANIMAL(S) Adult female rats from a urogenital research laboratory. INTERVENTION(S) Six rat dams randomly assigned to the following groups: control group (C), with free access to a standard laboratory diet containing 23% protein; and a protein-energy-restricted group (PER), with free access to an isoenergy and protein-restricted diet containing 8% protein. After weaning, the female pups had free access to the standard laboratory diet until 90 days of age, when they were sacrificed at the proestrum stage. MAIN OUTCOME MEASURE(S) Quantification of ovarian follicles, vessels, and expression of growth factors and their receptors. RESULT(S) Maternal malnutrition during lactation caused a significant reduction in the number of primordial (C = 6.60 +/- 0.24, PER = 5.20 +/- 0.20), primary (C = 5.80 +/- 0.66, PER = 4.00 +/- 0.31), and Graafian follicles/section (C = 2.18 +/- 0.29, PER = 1.08 +/- 0.37), in KDR (C = 0.22 +/- 0.04, PER = 0.09 +/- 0.01), Flt-1 (C = 0.28 +/- 0.05, PER = 0.12 +/- 0.02), and FGFR mRNA expression (C = 0.34 +/- 0.05, PER = 0.13 +/- 0.05) and in the vessel density of follicles (C = 17.26 +/- 2.30, PER = 9.96 +/- 0.97). CONCLUSION(S) Maternal malnutrition during lactation programs the follicular development by a reduction of VEGF and FGF mRNA receptors expression, probably from a direct action on the follicular development or a reduction in vasculature resulting in a decreased delivery of folliculotrophic substances in PER animals.
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Hamden K, Silandre D, Delalande C, Elfeki A, Carreau S. Protective effects of estrogens and caloric restriction during aging on various rat testis parameters. Asian J Androl 2009; 10:837-45. [PMID: 18958347 DOI: 10.1111/j.1745-7262.2008.00430.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
AIM To investigate the effects of 17beta-estradiol (E2), Peganum harmala extract (PHE) and caloric restriction (CR) on various testis parameters during aging. METHODS Twelve month-old male rats were treated for 6 months with either E2 or PHE, or submitted to CR (40%). RESULTS Our results show that estrogens and CR are able to protect the male gonad by preventing the decrease of testosterone and E2 levels as well as the decrease of aromatase and estrogen receptor gene expressions. Indeed, E2, PHE and CR treatments induced an increase in the superoxide dismutase activities and decreased the activity of testicular enzymes: gamma-glutamyl transferase, alkaline phosphatase, lactate deshydrogenase as well as the aspartate and lactate transaminases in aged animals. In addition, the testicular catalase and gluthatione peroxidase activities were enhanced in E2, PHE and CR-treated rats compared to untreated animals at 18 months of age. Moreover, the positive effects of estradiol, PHE and CR were further supported by a lower level of lipid peroxidation. Recovery of spermatogenesis was recorded in treated rats. CONCLUSION Besides a low caloric diet which is beneficial for spermatogenesis, a protective antioxydant role of estrogens is suggested. Estrogens delay testicular cell damage, which leads to functional senescence and, therefore, estrogens are helpful in protecting the reproductive functions from the adverse effects exerted by reactive oxygen species (ROS) produced in large quantities in the aged testis.
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Affiliation(s)
- Khaled Hamden
- Department of Animal Ecophysiology, Faculty of Sciences, University of Sfax, PB 802, Sfax 3018, Tunisia
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Govic A, Levay EA, Hazi A, Penman J, Kent S, Paolini AG. Alterations in male sexual behaviour, attractiveness and testosterone levels induced by an adult-onset calorie restriction regimen. Behav Brain Res 2008; 190:140-6. [DOI: 10.1016/j.bbr.2008.02.013] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2007] [Revised: 01/25/2008] [Accepted: 02/11/2008] [Indexed: 11/30/2022]
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Ojeda NB, Grigore D, Alexander BT. Developmental programming of hypertension: insight from animal models of nutritional manipulation. Hypertension 2008; 52:44-50. [PMID: 18474830 DOI: 10.1161/hypertensionaha.107.092890] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Norma B Ojeda
- Department of Physiology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505, USA
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Govic A, Kent S, Levay EA, Hazi A, Penman J, Paolini AG. Testosterone, social and sexual behavior of perinatally and lifelong calorie restricted offspring. Physiol Behav 2008; 94:516-22. [PMID: 18456293 DOI: 10.1016/j.physbeh.2008.03.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2007] [Revised: 02/22/2008] [Accepted: 03/12/2008] [Indexed: 11/17/2022]
Abstract
Calorie restriction (CR) during sensitive perinatal periods has consistently been demonstrated to alter the development of a variety of physiological systems, which consequently affect behavior. This study compared the social behavior and sexual behavior of the adult male offspring of mothers administered a 25% CR at one of four times in the perinatal period: a brief period preconception, during gestation, during lactation, or a lifelong restriction (beginning at conception and continuing throughout life). Levels of serum testosterone were also determined in these animals. Social interaction increased in the gestation and lifelong CR groups. The lifelong group also exhibited more dominant type behaviors. CR during preconception and lactation resulted in offspring that displayed an enhanced and more efficient copulatory pattern compared to all other conditions. This was demonstrated by a reduced frequency of intromissions, shorter latency to ejaculation, and a greater frequency of ejaculations by the preconception and lactation group compared to some, if not all of the other CR groups and controls. Serum testosterone was significantly higher in the preconception group compared to controls. These findings indicate that CR during specific periods of development can differentially alter the social behavioral phenotype and hormone levels in adulthood.
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Affiliation(s)
- Antonina Govic
- School of Psychological Science, La Trobe University, Bundoora, VIC 3086, Australia
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37
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Carreau S, Silandre D, Bourguiba S, Hamden K, Said L, Lambard S, Galeraud-Denis I, Delalande C. Estrogens and male reproduction: a new concept. Braz J Med Biol Res 2008; 40:761-8. [PMID: 17581673 DOI: 10.1590/s0100-879x2007000600003] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2007] [Accepted: 05/04/2007] [Indexed: 01/30/2023] Open
Abstract
The mammalian testis serves two main functions: production of spermatozoa and synthesis of steroids; among them estrogens are the end products obtained from the irreversible transformation of androgens by a microsomal enzymatic complex named aromatase. The aromatase is encoded by a single gene (cyp19) in humans which contains 18 exons, 9 of them being translated. In rats, the aromatase activity is mainly located in Sertoli cells of immature rats and then in Leydig cells of adult rats. We have demonstrated that germ cells represent an important source of estrogens: the amount of P450arom transcript is 3-fold higher in pachytene spermatocytes compared to gonocytes or round spermatids; conversely, aromatase activity is more intense in haploid cells. Male germ cells of mice, bank voles, bears, and monkeys express aromatase. In humans, we have shown the presence of a biologically active aromatase and of estrogen receptors (alpha and ss) in ejaculated spermatozoa and in immature germ cells in addition to Leydig cells. Moreover, we have demonstrated that the amount of P450arom transcripts is 30% lower in immotile than in motile spermatozoa. Alterations of spermatogenesis in terms of number and motility of spermatozoa have been described in men genetically deficient in aromatase. These last observations, together with our data showing a significant decrease of aromatase in immotile spermatozoa, suggest that aromatase could be involved in the acquisition of sperm motility. Thus, taking into account the widespread localization of aromatase and estrogen receptors in testicular cells, it is obvious that, besides gonadotrophins and androgens, estrogens produced locally should be considered to be physiologically relevant hormones involved in the regulation of spermatogenesis and spermiogenesis.
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Affiliation(s)
- S Carreau
- Department of Biochemistry, University of Caen, Caen, France.
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