Epigenetics and the Fetal Origins of Adult Health and Disease

Abundant evidence exists linking maternal and paternal environments from pericopconception through the postnatal period to later risk to offspring diseases. This concept was first articulated by the late Sir David Barker and as such coined the Barker Hypothesis. The term was then mutated to Fetal Origins of Adult Disease and finally broadened to developmental origins of adult health and disease (DOHaD) in recognition that the perinatal environment can shape both health and disease in resulting offspring. Developmental exposure to various factors, including stress, obesity, caloric-rich diets and environmental chemicals can lead to detrimental offspring health outcomes. However, less attention has been paid to date on measures that parents can take to promote the long-term health of their offspring. In essence, have we neglected to consider the ‘H’ in DOHaD? It is the ‘H’ component that should be of primary concern to expecting mothers and fathers and those seeking to have children. While it may not be possible to eliminate exposure to all pernicious factors, prevention/remediation strategies may tip the scale to health rather than disease. By understanding disruptive DOHaD mechanisms, it may also illuminate behavioral modifications that parents can adapt before fertilization and throughout the neonatal period to promote the lifelong health of their male and female offspring. Three possibilities will be explored in the current review: parental exercise, probiotic supplementation and breastfeeding in the case of mothers. The ‘H’ paradigm should be the focus going forward as a healthy start can indeed last a lifetime.

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Fetal Origins of Adult Health and Disease

Genetic Disorders and the Fetus ◽

10.1002/9781119676980.ch5 ◽

2021 ◽

pp. 214-239

Author(s):

Michael G. Ross ◽

Mina Desai

Keyword(s):

Adult Health ◽

Fetal Origins ◽

Health And Disease

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Perinatal Genomics

Annual Review of Nursing Research ◽

10.1891/0739-6686.29.331 ◽

2011 ◽

Vol 29 (1) ◽

pp. 331-351 ◽

Cited By ~ 1

Author(s):

Gwen Latendresse

Keyword(s):

Gene Expression ◽

Preterm Birth ◽

Regulation Of Gene Expression ◽

Tobacco Smoke Exposure ◽

Adult Health ◽

Perinatal Complications ◽

Fetal Origins ◽

Health And Disease ◽

The Impact ◽

Pathophysiologic Mechanisms

Significant maternal, fetal, and newborn morbidity and mortality can be attributed to complications of pregnancy. There are direct links between perinatal complications and poor fetal/newborn development and impaired cognitive function, as well as fetal, newborn, and maternal death. Many perinatal complications have pathophysiologic mechanisms with a genetic basis. The objective of this chapter is to focus on perinatal genomics and the occurrence of two specific complications: preterm birth and dysfunctional placental phenotype. This chapter includes discussions of genetic variation, mutation and inheritance, gene expression, and genetic biomarkers in relation to preterm birth, in addition to the impact of maternal tobacco smoke exposure on placental phenotype. The concept of epigenetics is also addressed, specifically the regulation of gene expression in the placenta and fetal origins of adult health and disease. There is great potential for nurse-researchers to make valuable contributions to perinatal genomics investigations, but this requires perseverance, increased genetics-based understanding and skills, as well as multidisciplinary mentorship.

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Epigenetics and the Fetal Origins of Adult Health and Disease

The Rise of Fetal and Neonatal Physiology ◽

10.1007/978-1-4939-7483-2_16 ◽

2018 ◽

pp. 501-534

Author(s):

Lawrence D. Longo

Keyword(s):

Adult Health ◽

Fetal Origins ◽

Health And Disease

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Self-reported physical health status of donor sperm-conceived adults

Journal of Developmental Origins of Health and Disease ◽

10.1017/s204017442000080x ◽

2020 ◽

pp. 1-14

Author(s):

Damian H. Adams ◽

Adam Gerace ◽

Michael J. Davies ◽

Sheryl de Lacey

Keyword(s):

Health Outcomes ◽

Acute Bronchitis ◽

Sleep Apnoea ◽

Developmental Origins ◽

Adult Health ◽

Physical Health Status ◽

Donor Sperm ◽

Health And Disease

Abstract Donor-conceived neonates have poorer birth outcomes, including low birth weight and preterm delivery that are associated with poorer long-term health in adulthood through the developmental origins of health and disease (DOHaD) theory. The aim of this study was to conduct the first investigation of the adult health outcomes of donor-conceived people. An online health survey was completed by 272 donor sperm-conceived adults and 877 spontaneously conceived adults from around the world. Donor and spontaneously conceived groups were matched for age, sex, height, smoking, alcohol consumption, exercise, own fertility and maternal smoking. Donor sperm-conceived adults had significantly higher reports of being diagnosed with type 1 diabetes (P = 0.031), thyroid disease (P = 0.031), acute bronchitis (P = 0.008), environmental allergies (P = 0.046), sleep apnoea (P = 0.037) and having ear tubes/grommets surgically implanted (P = 0.046). This is the first study to investigate the health outcomes of adult donor sperm-conceived people. Donor sperm-conceived adults self-reported elevated frequencies of various health conditions. The outcomes are consistent with birth defect data from donor sperm treatment and are consistent with the DOHaD linking perturbed early growth and chronic disease in adulthood.

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Prenatal Developmental Origins of Future Psychopathology: Mechanisms and Pathways

Annual Review of Clinical Psychology ◽

10.1146/annurev-clinpsy-050718-095539 ◽

2019 ◽

Vol 15 (1) ◽

pp. 317-344 ◽

Cited By ~ 38

Author(s):

Catherine Monk ◽

Claudia Lugo-Candelas ◽

Caroline Trumpff

Keyword(s):

Maternal Distress ◽

Developmental Origins ◽

Neurodevelopmental Outcomes ◽

Fetal Origins ◽

Behavior Development ◽

Increased Risk ◽

Health And Disease ◽

Brain And Behavior ◽

And Behavior ◽

The Impact

The developmental origins of health and disease hypothesis applied to neurodevelopmental outcomes asserts that the fetal origins of future development are relevant to mental health. There is a third pathway for the familial inheritance of risk for psychiatric illness beyond shared genes and the quality of parental care: the impact of pregnant women's distress—defined broadly to include perceived stress, life events, depression, and anxiety—on fetal and infant brain–behavior development. We discuss epidemiological and observational clinical data demonstrating that maternal distress is associated with children's increased risk for psychopathology: For example, high maternal anxiety is associated with a twofold increase in the risk of probable mental disorder in children. We review several biological systems hypothesized to be mechanisms by which maternal distress affects fetal and child brain and behavior development, as well as the clinical implications of studies of the developmental origins of health and disease that focus on maternal distress. Development and parenting begin before birth.

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The Roles of PPARs in the Fetal Origins of Metabolic Health and Disease

PPAR Research ◽

10.1155/2008/459030 ◽

2008 ◽

Vol 2008 ◽

pp. 1-8 ◽

Cited By ~ 35

Author(s):

William D. Rees ◽

Christopher J. McNeil ◽

Christopher A. Maloney

Keyword(s):

Epigenetic Modification ◽

Fetal Liver ◽

Maternal Diet ◽

Subsequent Development ◽

Adaptive Responses ◽

Fetal Origins ◽

Methylation Of Dna ◽

Health And Disease ◽

Cell Growth And Differentiation

Beyond the short-term effects on fertility, there is increasing evidence that obesity or the consumption of an inappropriate diet by the mother during pregnancy adversely affects the long-term health of her offspring. PPAR and RXR isotypes are widely expressed in reproductive tissues and in the developing fetus. Through their interactions with fatty acids, they may mediate adaptive responses to the changes in the maternal diet. In the maturing follicle, PPAR-γhas an important role in the granulosa cells that surround the maturing oocyte. After fertilisation, PPAR-γand PPAR-β/δare essential regulators of placentation and the subsequent development of key metabolic tissues such as skeletal muscle and adipose cells. Activation of PPAR-γand PPAR-β/δduring fetal development has the potential to modify the growth and development of these tissues. PPAR-αis expressed at low levels in the fetal liver, however, this expression may be important, as changes in the methylation of DNA in its promoter region are reported to take place during this period of development. This epigenetic modification then programmes subsequent expression. These findings suggest that two separate PPAR-dependent mechanisms may be involved in the fetal adaptations to the maternal diet, one, mediated by PPAR-γand PPAR-β/δ, regulating cell growth and differentiation; and another adapting long-term lipid metabolism via epigenetic changes in PPAR-αto optimise postnatal survival.

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Killing Me Softly: The Fetal Origins Hypothesis

The Journal of Economic Perspectives ◽

10.1257/jep.25.3.153 ◽

2011 ◽

Vol 25 (3) ◽

pp. 153-172 ◽

Cited By ~ 539

Author(s):

Douglas Almond ◽

Janet Currie

Keyword(s):

Type 2 Diabetes ◽

Heart Disease ◽

Educational Attainment ◽

Test Scores ◽

Later Life ◽

Observational Evidence ◽

Adult Health ◽

Fetal Origins ◽

Fetal Origins Hypothesis

In the epidemiological literature, the fetal origins hypothesis associated with David J. Barker posits that chronic, degenerative conditions of adult health, including heart disease and type 2 diabetes, may be triggered by circumstances decades earlier, particularly, by in utero nutrition. Economists have expanded on this hypothesis, investigating a broader range of fetal shocks and circumstances and have found a wealth of later-life impacts on outcomes including test scores, educational attainment, and income, along with health. In the process, they have provided some of the most credible observational evidence in support of the hypothesis. The magnitude of the impacts is generally large. Thus, the fetal origins hypothesis has not only survived contact with economics, but has flourished.

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Transcriptional sexual dimorphism during preimplantation embryo development and its consequences for developmental competence and adult health and disease

Reproduction ◽

10.1530/rep-10-0482 ◽

2011 ◽

Vol 141 (5) ◽

pp. 563-570 ◽

Cited By ~ 75

Author(s):

P Bermejo-Alvarez ◽

D Rizos ◽

P Lonergan ◽

A Gutierrez-Adan

Keyword(s):

Sexual Dimorphism ◽

Sex Chromosome ◽

Developmental Competence ◽

Preimplantation Embryos ◽

Adult Health ◽

Long Term Effects ◽

Preimplantation Embryo Development ◽

Phenotypic Differences ◽

Hormone Effects ◽

Health And Disease

In adult tissues, sexual dimorphism is largely attributed to sex hormone effects, although there is increasing evidence for a major role of sex chromosome dosage. During preimplantation development, male and female embryos can display phenotypic differences that can only be attributed to the transcriptional differences resulting from their different sex chromosome complements. Thus, all expressed Y-linked genes and those X-linked genes that totally or partially escape X-chromosome inactivation at each specific developmental stage display transcriptional sexual dimorphism. Furthermore, these differentially expressed sex chromosome transcripts can regulate the transcription of autosomal genes, leading to a large transcriptional sexual dimorphism. The sex-dependent transcriptional differences may affect several molecular pathways such as glucose metabolism, DNA methylation and epigenetic regulation, and protein metabolism. These molecular differences may have developmental consequences, including sex-selective embryo loss and sex-specific epigenetic responses to environmental hazards, leading to long-term effects. This review discusses transcriptional sexual dimorphism in preimplantation embryos, its consequences on sex ratio biases and on the developmental origin of health and disease, and its significance for transcriptional studies and adult sexual dimorphism.

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