Sex, Gender, and Epigenetics

From Molecule to Bedside

1st Edition - May 23, 2023
Editors: Marianne Legato J, Dov Feldberg, Marek Glezerman
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 2 3 9 3 7 - 7
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 3 9 3 8 - 4

Sex, Gender, and Epigenetics: From Molecule to Bedside explores our expanding knowledge of the science of epigenetics in which gene expression is modified as a consequence of sma… Read more

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Sex, Gender, and Epigenetics: From Molecule to Bedside explores our expanding knowledge of the science of epigenetics in which gene expression is modified as a consequence of small chemical additions to various components of the genome. The book provides an overview of the field, describing the epigenetic phenomena that unite biological sex and environmental experience to create the unique phenome of each individual. The book also analyzes the impact of ancestors’ environmental experience on subsequent generations through the sex-specific transmission of environmentally induced epigenetic modifications.

Here, international leaders in the field discuss both sex-specific normal physiology and the experience of disease, with chapters dedicated to fetal programming, the microbiome, cancer, bipolar disorder and schizophrenia, embryogenesis, and oocyte aging, among other topics.

Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Chapter 1: Exploring how we become what we are
Abstract
1.1: Introduction
1.2: Lamarck, Darwin, and Waddington: Developing the concept of the impact of environment on the phenotype
1.3: Moving into and past the 20th century: Meloni's concept of “hard heredity”
1.4: The 21st century ushers in the postgenomic era and the period of “soft heredity”
1.5: What underlies the swell of interest in epigenetics?
1.6: The Gordian knot of sex and gender
1.7: Symposium: Aims and composition
1.8: The exposome
1.9: Conclusion
References
Chapter 2: A critical view of the revolution of precision medicine: genetics, epigenetics, sex, and gender
Abstract
Acknowledgments
2.1: The increase in age-related disorders
2.2: Recent developments in biomedical sciences
2.3: A brief look at the history of drugs
2.4: Personalized medicine versus precision medicine
2.5: Accessibility and affordability
2.6: Privacy of biomedical data
2.7: Gender- and sex-conscious medicine
References
Chapter 3: Genetic and epigenetic contributions to female-biased lupus disease: X-chromosome inactivation in immune cells
Abstract
3.1: Introduction
3.2: X-chromosome inactivation (XCI): An epigenetic mechanism for dosage compensation in mammals
3.3: “Dynamic XCI maintenance” in female lymphocytes
3.4: Dynamic XCI maintenance during lymphocyte development and other immune cells
3.5: Mislocalization of Xist RNA and heterochromatic marks at the Xi is a feature of female-biased lupus disease
References
Chapter 4: Genetic, molecular, and cellular determinations of sex-specific cardiovascular traits
Abstract
4.1: Introduction
4.2: Hormones—The classical explanation for physiological sex differences
4.3: Women-specific risk factors
4.4: CVD sex differences in DNA
4.5: Epigenetic sex differences
4.6: Moving forward
References
Chapter 5: Epigenetics and mental and physical health of children born after ART
Abstract
5.1: Introduction
5.2: Major malformations
5.3: Epigenetic and genetic abnormalities
5.4: Outcome regarding timing of transfer
5.5: Cognitive and mental health of children born after ART
5.6: New techniques
5.7: Neoplasms in children born after ART
References
Chapter 6: Epigenetic aspects of male infertility treatment
Abstract
6.1: Background
6.2: Epigenetics of fertilization
6.3: Embryo developmental competence of the male gamete
6.4: Genomic profiling of the spermatozoon
6.5: Epigenetic predictor of spermatogenesis
6.6: Conclusion
References
Chapter 7: Evidence for assisted reproductive technology associated epigenetic variation in humans
Abstract
7.1: Introduction to assisted reproductive technology
7.2: Epigenetic processes
7.3: Unanswered questions
7.4: Conclusion
References
Chapter 8: Deconvoluting the functional role of DNA methylation in trauma; Implications for epigenetic therapy and prospects of targeted “epigenetic therapy”
Abstract
8.1: Introduction
8.2: Differential methylation profiles between resilient and susceptible animals
8.3: Differences in expression of the DNA methylating enzyme DNMT3A in NAc between the susceptible and resilient animals
8.4: RORA is an upstream regulator of pathways enriched with differentially methylated genes between susceptible and resilient animals
8.5: Overexpression of Dnmt3a and Rora in the NAc converts susceptible animals to resilient while knockdown of Dnmt3a and Rora converts “resilient” animals to “susceptible”
8.6: A combination of retinoic acid and SAMe supplementation reverses PTSD-like behaviors
8.7: The methylation profile of a fetus is altered in a sex specific manner by genetic depletion of the glucocorticoid receptor gene (Nr3c1)
8.8: Developing new tools to determine causality of DNA methylation alteration in PTSD; Prospects for directed epigenetic therapy
8.9: Prospects
8.10: Summary
References
Chapter 9: Antenatal Origins of Health and Disease—A clinician's perspective
Abstract
9.1: Successful aging may start before conception
9.2: The concept of fetal programming
9.3: From gametes to the embryo
9.4: Antenatal origins of health and disease
9.5: The epigenome as target for diagnosis and treatment
9.6: Outlook
References
Chapter 10: Maternal anxiety during pregnancy and the lack of fetal DNA methylation in cord blood
Abstract
Acknowledgments
10.1: Introduction
10.2: Methods
10.3: Results
10.4: Discussion
10.5: Future direction
10.6: Conclusion
References
Chapter 11: DNA methylation and other epigenetic modifications mediating the transgenerational impacts of paternal exposures on offspring phenotypes
Abstract
11.1: Introduction
11.2: Epigenetic re-programming and regulation of genomic DNA methylation
11.3: Methylation-based epigenetic mechanisms potentially influencing offspring phenotypes
11.4: Topologically associated domains
11.5: Focus studies of paternal stress-associated epigenetic inheritance
11.6: Conclusion
References
Chapter 12: Epigenetics and psychiatry
Abstract
Acknowledgments
12.1: Introduction
12.2: Outline of history of epigenetics and psychiatry
12.3: Potential role for epigenetics in psychiatric disorders
12.4: Environmental factors and epigenetics and psychiatry
12.5: Current status of molecular data in epigenetics and psychiatry
12.6: Dual role for genetics and epigenetics in psychiatric disorders
12.7: New developments in epigenetics and psychiatry
12.8: Clinical implications of epigenetics and psychiatry
12.9: Transgenerational inheritance and epigenetics and psychiatry
12.10: Taking epigenetics and psychiatry forward
12.11: Conclusions
References
Further reading
Chapter 13: Integrative transcriptomics reveals sexually dimorphic control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder
Abstract
13.1: Introduction
13.2: Methodological approach
13.3: Results
13.4: Discussion
References
Chapter 14: Gender specific neurobehavioral and gene expression changes in a valproic acid (VPA)–induced mouse model of autistic like behavior and correction by S-adenosylmethionine (SAMe)
Abstract
14.1: Autism spectrum disorder in human and animal models: Gender differences and pathophysiology
14.2: Epidemiology of ASD
14.3: Clinical presentation and gender differences of ASD
14.4: Animal models of ASD
14.5: The mechanisms of VPA teratogenicity
14.6: Postnatal studies
14.7: Studies of gene expression in the brain
14.8: Prenatal studies
14.9: Conclusions
References
Chapter 15: Genetics and epigenetics of the one-carbon metabolism pathway in autism spectrum disorder: Role of a sex-specific brain epigenome
Abstract
15.1: Introduction
15.2: Developmental origin of health and disease theory
15.3: Genomic imprinting
15.4: X-chromosome inactivation (XCI)
15.5: Conflict hypothesis of genomic imprinting
15.6: Methylation mechanisms by one-carbon units and involved genes
15.7: Autism spectrum disorder (ASD) and brain epigenome
15.8: Conclusions
References
Chapter 16: Novel mechanisms for gene regulation: Chemical tags on RNA molecules
Abstract
16.1: Introduction
16.2: Writer, erasers, and readers of m6A
16.3: Misregulation of neuronal development by m6A and associated neuropathologies
16.4: Regulation of glial development by m6A and associated pathologies
16.5: Regulation of behavior by m6A
16.6: Conclusion and future directions
References
Chapter 17: Genes, environments, and epigenetics
Abstract
Acknowledgments
17.1: Introduction
17.2: Individual differences and the foraging gene
17.3: The foraging gene and a mechanistic basis for pleiotropy
17.4: Epigenetics
17.5: Conclusion
References
Chapter 18: Epigenetic mechanisms linking poor maternal nutrition during pregnancy to the cardio-metabolic health of offspring
Abstract
1: Introduction to programming
2: Obesity during pregnancy and its short-term consequences
3: Programming by maternal obesity during pregnancy
4: Intervention strategies to prevent programming by maternal obesity
5: Mechanisms that could underly sex differences in developmental programming
6: Conclusion
References
Chapter 19: Epigenetic aspects of human reproduction and early pregnancy
Abstract
19.1: Definition and mechanisms
19.2: Epigenetic impact in molar pregnancy
19.3: Epigenetic changes and trisomy and monosomy in humans
19.4: The impact of epigenetics on antiphospholipid syndrome
19.5: Antiepigenetic impact of drugs
19.6: Types of epigenetic processes
19.7: Clinical epigenetics
19.8: Epigenetics and ART
19.9: Resolvement of epigenetic marks
19.10: Psychological stress in pregnancy and the impact on fetal development
19.11: Long-term impact of folic acid in pregnancy on offspring DNA methylation
19.12: Epigenetics and placenta
References
Chapter 20: Sex-specific impact of maternal metabolic environment on the development of the offspring, from gametogenesis to infancy and beyond
Abstract
20.1: Sex-specific impact of maternal metabolic environment
20.2: Sex-specific impact of maternal obesity on the feto-placental development
20.3: Conclusion
References
Chapter 21: Mitochondria as epigenetic regulators of reproductive aging
Abstract
Acknowledgments
21.1: Introduction
21.2: Results
21.3: Future direction
21.4: Conclusion
References
Chapter 22: The fetal programming of telomere biology hypothesis
Abstract
Acknowledgments
22.1: Introduction
22.2: How does maternal stress during pregnancy affect fetal development and susceptibility to disease?
22.3: What mechanisms drive the association between maternal stress and the offspring's susceptibility to disease in later life?
22.4: How, if at all, can the adverse effects of maternal stress on fetal development be prevented or reversed?
22.5: Conclusion
References
Chapter 23: Brain organoids modeling of genetic and environmental impact on neurodevelopmental traits
Abstract
23.1: Introduction
23.2: Neurodevelopmental disorders: Clinical and molecular convergences
23.3: Environmental factors associated with NDDs: The role of EDCs
23.4: Reprogramming and brain organoid technologies
23.5: From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
23.6: Multiplexing strategies to study the effects of chemicals on multiple genetic backgrounds
23.7: Investigating epigenetic inheritance with human in vitro models
References
Index

Marianne Legato J

Dr. Marianne Legato, Emerita Professor of Clinical Medicine at Columbia University, is an internationally known academic physician, author, lecturer, and specialist in gender-specific medicine. She is founding member of the International Society for Gender Medicine and the founder and director of The Partnership for Gender-Specific Medicine at Columbia University and its next iteration, The Foundation for Gender-Specific Medicine. She has published extensively on gender and sex specific medicine, both for the scientific community and for the lay public. She is also the founding editor of the Journal Gender Medicine, and the journal Gender and the Genome. In 1992, Dr. Legato won the American Heart Association’s Blakeslee Award for the best book written for the lay public on cardiovascular disease. The third edition of her textbook, Principles of Gender-Specific Medicine and her most recent book, The Plasticity of Sex., both won Prose awards from the American Association of Editors in 2021 and 2022 respectively. She is a practicing internist in New York City and has been listed each year in New York Magazine and Castle Connolly’s lists "Best Doctors" since their inception in 1993.

Affiliations and expertise

Emerita Professor, Clinical Medicine, Columbia University College of Physicians & Surgeons and Adjunct Professor, Medicine at Johns Hopkins Medical School

Dov Feldberg

Dr. Dov Feldberg, MD is a very active clinically and academically Ob/Gyn specialist mainly in the field of reproductive medicine for 37 years. He obtained his expertise in Reproductive Medicine at the Yale and Cornell Hospitals and Universities in USA and became one of the pioneers in the field of ART in Israel. He was an Acting Chairman and Vice Chairman of the Ob/Gyn Division at the Rabin Medical Center in Israel. For many years he was the secretary and treasurer of the The Israel Society for Gender-and Sex Conscious Medicine (IsraGem) and the treasurer of the International Society of Gender Medicine (IGM). He is the president of the Israeli Society of Psychosomatics in Ob/Gyn. He published about 130 scientific articles in the field of Reproductive Medicine and many chapters in books. He organizes national and international meetings in the field of his interest and activities.

Affiliations and expertise

Professor, Department of Obstetrics & Gynecology, Tel Aviv University School of Medicine, Tel Aviv, Israel

Marek Glezerman

Dr. Marek Glezerman, MD has chaired for 25 years in succession three large departments of Obstetrics and Gynecology at major health care centers in Israel. He has also acted for 14 years as chairman of the National Steering Committee of ObGyn at the Maccabi Health Care Services in Israel. Since 20108, he has been deeply involved in research and promotion of Gender and Sex Conscious Medicine and is regarded as one of its pioneers on a national and international level. Prof. Glezerman is founding president of the Israel Society for Gender- and Sex-Conscious Medicine and past-president of the International Society for Gender Medicine. He is currently Head of Gender- and Sex-Conscious Medicine at Tel Aviv University. He has written/edited 6 books and published more than 340 scientific articles in professional journals and chapters in textbooks.

Affiliations and expertise

Professor (emeritus) of Obstetrics and Gynecology, Faculty of Medicine, Tel Aviv University, Isreal Current Head of Gender and Sex Conscious Medicine , Chairman of the Ethics Committee, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel