Epigenetics and Reproductive Health (Volume 21) (Translational Epigenetics, Volume 21)

Translational Epigenetics Series
Epigenetics and Reproductive Health
Dedication
Copyright
Contributors
Acknowledgment_2021_Epigenetics-and-Reproductive-Health
Introduction to epigenetics: basic concepts and advancements in the field
	Introduction
	Epigenetics
		Definition
		DNA methylation
			DNA methylation: establishment and erasure
		Histone modifications
		Higher-order chromatin organization
			Histone acetylation
			Histone methylation
			Other histone modifications
		The “Histone Code”- its writers, readers and erasers
		Non-coding RNAs
		RNA modifications
	Techniques for epigenetic analysis
		DNA methylation
		Histone modifications and chromatin remodelling
		Methods to analyze methylation of RNA and ncRNA-species
		Analysis of epigenetic modulating enzymes and their functions
	Single cell epigenomics
		Methodologies for single cell epigenetic analysis
		DNA methylation and other modification
		Histone modifications and transcription factor binding
		Chromatin structure and chromosome organization
	Epigenome manipulation and editing
		Epigenetic manipulation techniques
		Small-molecule inhibitors
		Targeted epigenome manipulations
			Zinc finger proteins
			TALEs
			CRISPR/Cas9 system
	References
1. Epigenome reprogramming in the male and female germ line
	Introduction
	Reprogramming of mouse germ cells
		Primordial germ cell development in mice
		Induction of PGCs from mouse pluripotent stem cells
		Epigenome reprogramming of mouse PGCs
			Transcriptional program for the mPGC fate
			Remodeling of histone modification during mPGC development
			Outline of DNA methylation reprogramming during mPGC development
			Details of DNA methylation reprogramming
			DNA hydroxymethylation
			Interplay between UHRF1 and H3K9me2 reduction
			Interplay between DNA demethylation and H3K9me3
			Interplay between DNA demethylation and histone remodeling
		Epigenome in sexually differentiated germ cells in mice
			Epigenome reprogramming and female germ cell pathway
			Androgenic epigenome programming in male embryonic germ cells
			Epigenome aberration during in vitro differentiation of male germ cells
		Summary of the epigenome reprogramming of embryonic germ cell development
		Oocytes form a unique epigenome during oogenesis
			De novo DNA methylation and genomic imprinting during oogenesis
			Interplay between histone modification and de novo DNA methylation
			Broad domains of H3K4me3 during oogenesis
			Histone replacement during oogenesis
			Three-dimensional organization during oogenesis
	Epigenome reprogramming during the development of human germ cells
		PGC specification and migration in human embryos
		Reconstitution of early human PGCs and epigenome reprogramming in vitro
			Human pluripotent stem cells
			Induction of human PGC-like cells and their signaling and transcriptional regulation
			Reprogramming of human PGCs reconstituted in vitro
		Sex-specific differentiation of human germ cells
			Differentiation of female germ cells
			Differentiation of male germ cells
		Epigenome reprogramming during development of human germ cells in genital ridges
		Epigenome reprogramming in human oogonia reconstituted in vitro
	Concluding remarks
	Glossary
	Acknowledgments
	References
2. Genomic imprinting
	Introduction
		Characteristics of imprinted genes
		The life cycle of imprints
		Genomic imprinting in embryogenesis
	Genomic imprinting in placentation
	Genomic imprinting in post-natal development
	Genomic imprinting in disease conditions
		Infertility
	Pregnancy-related disorders
	Genetic and environmental influences on genomic imprinting
	Genetic influences
	Environmental influences
		Endocrine disruptors
	Assisted reproductive technologies induced defects
	Concluding remarks
	References
3. Chromatin remodeling of the male genome during spermiogenesis and embryo development
	Introduction
	Nuclear remodeling in sperm
		Eviction of somatic histones and accompanying events
			Hyperacetylation of histones
			DNA strand breaks
			Transcriptional surge
		Incorporation of testis specific histone variants
		Histone replacement by protamines
	From being sperm nucleus to paternal pronucleus
		Genome-wide reprogramming at fertilization
			Zygotic Genome Activation
			Methylation - demethylation
	Is sperm merely a vector for the paternal genome?
		The “not-so-small” importance of sperm small RNA population
		Sperm miRNAs
			Sperm non-coding RNAs
	Father\'s extra-genomic contribution to the zygote
	References
4. Epigenetic regulation in stem cells
	History of stem cell research
	Types of stem cells
	Induced pluripotent stem cells (iPSCs)
	Mechanism on the self-renewal of PSCs
	Core transcription factors
		OCT4
		Nanog
	Signal transduction pathways
	LIF-STAT pathway
	Wnt pathway
	TGF-β pathway
	Epigenetics
	DNA methylation
	Histone modification
	Chromatin remodeling
	Three-dimensional structure of genome
	Conclusion
	References
5. Aberrant epigenetics and reproductive disorders
	Epigenetic alterations and reproductive system
	Role of epigenetic alterations in female infertility
		Polycystic ovary syndrome
		Endometriosis
		DNA methylation
		Modification of histone code
		Short non-coding RNAs and endometriosis
		HDAC inhibitor in the treatment of endometriosis
	Premature ovarian failure
	Male infertility and DNA methylation
		Methylation of imprinted genes and global/genome-wide and gene-specific methylation
		Global/genome-wide and gene-specific DNA methylation
		Histone modifications and male infertility
		Role of protamination in male infertility
		Non-coding RNAs and male infertility
	Conclusion
	References
6. Epigenetic reprogramming in the embryo
	Introduction
	Epigenetics, a brief overview
	Epigenetic marks that are relevant to preimplantation development
		DNA methylation
		5-Hydroxymethylcytosine (5hmC)
		Histone modifications
	Epigenetic reprogramming in the zygote and preimplantation embryo: an overview
	The gametes and their epigenetic characteristics
	The zygote: a hotbed of epigenetic activity
		Regulation of DNA methylation in the zygote
		Regulation of histones and histone modifications in the zygote
	Detailed mapping of methylation changes in preimplantation development
	Mediators of DNA methylation in gametes and preimplantation embryos
	The subcortical maternal complex is a key effector of epigenetic programming in the oocyte/early embryo
	Demethylation events in the zygote and preimplantation embryo
	Species-specific differences in reprogramming
	RNA as a mediator of epigenetic events in gametes and preimplantation embryos
	Conclusions
	References
7. Epigenetic regulation during placentation
	The placenta
		Description of the placenta and placental cells
			Structure of human placenta
			Placental cells
				Cytotrophoblasts and syncytiotrophoblasts
				Villous core stroma cells
				Pericytes and endothelial cells
			How does the placenta form?
		Human placental development from fertilization to full term
			Early placenta formation
			Transition to the primitive villous tree
			Establishment of the maternofetal barrier
		Placental blood circulation and spiral artery remodeling
			Maternal-placental circulation systems
			Spiral artery remodeling
			Fetal placental circulation system
		Placental physiology
			Feto-maternal exchange through placenta
			Breathing function
			Nutritive and excretory functions
			Endocrinal function
	Epigenetic mechanisms in placental development
		DNA methylation
		Non-coding RNAs
			miRs
				miRs in trophoblast proliferation
				miRs in trophoblast invasion, migration, and differentiation
				miRs in placental vascularization and angiogenesis
			Long non-coding RNAs (lncRNAs)
		Histone modifications
		Imprinting and placental development
			H19-IGF2 cluster
		The pseudo malignant placental epigenome
	Disturbed placental epigenetics
		Placental epigenetics in relation to placental-related pathologies
			Preeclampsia
			Intra uterine growth restriction (IUGR)
			Gestational diabetes (GDM)
		Environmental effects
			Diet
			Effects of alcohol on placental epigenetics
			Assisted reproductive technology
		Maternal metabolic diseases
			Thyroid dysfunction
			Obesity
	Conclusions and future perspectives
	References
8. Epigenetic modulation during pregnancy and pregnancy related disorders
	Introduction
	Epigenetic regulation of placenta during pregnancy
		DNA methylation
		Chromatin remodeling
		MicroRNAs
	Epigenetics and pathogenesis of pregnancy disorders
		Miscarriage and preterm birth
			DNA methylation
			Chromatin remodeling
			MicroRNAs
		Fetal growth restriction (FGR)
			DNA methylation
			Chromatin remodeling
			MicroRNAs
		Preeclampsia
			DNA methylation
			Chromatin remodeling
			MicroRNAs
		Gestational diabetes
			DNA methylation
			Chromatin remodeling
			MicroRNAs
	Conclusion
	References
9. Epigenetic involvement in fetal and neonatal origins of late-onset disease
	Introduction
	Fetal origins of late-onset disease and the underlying epigenetic mechanism
	Neonatal origins of late-onset disease and the underyling epigenetic mechanism
	Transgenerational epigenetic inheritance
	Medical and educational intervention in early life to correct epigenetic dysfunctions
	Conclusion
	Acknowledgments
	References
10. Impact of environmental chemicals and endocrine disruptors on mammalian germ cell epigenome
	Introduction
	Epigenetic effects of EDCs on male germ cell development
		DNA methylation
		ncRNAs
		Post-translational modifications of histones and chromatin remodeling
	Epigenetic effects of EDCs on female germ cell development
	Transgenerational epigenetic inheritance
	Conclusions and research perspectives
	References
11. Influence of nutrition on reproductive health through epigenetic mechanisms
	List of abbreviations
	Introduction
	Nutrition and reproductive health
	Macronutrients
	Micronutrients
	Nutrition and developmental origins of health and disease (DOHaD)
	One carbon metabolism
	Epigenetics
	Maternal nutrition, epigenetics and reproductive health
		Preeclampsia
	Gestational diabetes mellitus (GDM)
	Preterm birth (PTB)
	Intrauterine growth restriction (IUGR)
	Paternal nutrition, epigenetics and reproductive health
	Conclusion
	References
12. Influence of stress and lifestyle on epigenetic modifications
	Introduction
	The influence of stress during prenatal life on epigenetic modifications of the offsprings
		The epigenetic changes of the offsprings upon exposure to stress in prenatal life due to disasters
		The epigenetic changes of the imprinted genes in offsprings due to stress during prenatal period
	Epigenetic changes of the HPA axis related genes in offsprings upon exposure to prenatal stress
	Epigenetic changes of the spermatozoa due to the paternal lifestyle
	Epigenetics and assisted reproductive technologies (ART)
	Conclusions
	References
13. Aging of male and female gametes
	Introduction
		Increasing age of parents
		Implications of advanced parental age
		Epigenetics
			Epigenetics of the male gamete
			Epigenetics of the female gamete
			Epigenetics of the developing embryo
	Aging in sperm
		Chromatin modifications
		DNA methylation
		ncRNAs
		Aging calculator
	Aging in oocytes
	Conclusion
		Senescence
	References
14. Testicular and prostate cancers
	Introduction
	Male reproductive cancers
		Testicular cancer
		Prostate cancer
	Genetic and epigenetic interplay in reproductive cancers
	Epigenetic regulation of testicular cancer
		DNA methylation
		Histone modification
		MicroRNAs
	Epigenetic regulation of prostate cancer
		DNA methylation
		Histone modification
		MicroRNAs
	Clinical implication of testicular and prostate cancer epigenetics
		Epigenetic biomarkers in testicular cancer
		Therapeutic targets in testicular cancer
		Epigenetic biomarkers in prostate cancer
		Therapeutic targets in prostate cancer
	Conclusions
	Acknowledgments
	References
15. Emerging patterns and implications of breast cancer epigenetics: an update of the current knowledge
	Introduction
		Risk factors
		Classification
		Methylation and cancer
		Control of transcription by methylation
		Methylomics of breast cancer: DNA methylation and gene dysregulation as a promising landscape for breast cancer prediction,...
			BRCA1
			CDH1
			APC
			CCND2
			PTEN
			GSTP1
			p16INK4α
			RASSF1A
			RAR-β2
		Histone modifications in breast cancer
		Noncoding RNAs influence on epigenetic alterations in breast cancer
		Circular RNAs
		Epigenetic landscape in breast cancer stem cells
		The potential utility of liquid biopsy-based epigenetic studies in breast cancer
		Epigenetic therapy of breast cancer
		Nucleoside analogs
		Non-nucleoside analogs
	Conclusion
	Acknowledgments
	References
16. Ovarian & endometrial cancers
	Epidemiology of endometrial and epithelial ovarian cancer
	Epigenetics of endometrial and epithelial ovarian cancer
		DNA methylation in endometrial cancer
		DNA methylation in ovarian cancer
	Epigenetic therapy in endometrial and ovarian cancer
		Role of non-coding RNAs in ovarian and endometrial cancer
	ncRNA transcripts in ovarian cancer and endometrial cancer
		Small ncRNAs
		miRNA
	Conclusion
	References
17. Epigenetic aberrations in cervical cancer
	Introduction
	Epigenetic alterations in cervical cancer
		DNA methylation
		Histone modifications
			Histone acetylation and deacetylation
			Histone methylation and demethylation
			Histone phosphorylation
	Influence of epigenetic alterations on cancer hallmarks
		Sustained proliferative signaling
		Limitless proliferation
		Evasion of apoptosis
		Migration and metastasis
		Angiogenesis
		Inflammation
	Therapeutics
	Conclusion
	References
18. Natural molecules as epigenetic modifiers in reproduction
	Introduction
	Folic acid (FA)
	Players in the endocannabinoid system
	Role of ECS in female reproductive system
	Role of ECS in male reproductive system
	Epigenetic effects on reproduction by cannabinoids
	Multigenerational effects of cannabis
	Conclusion
	References
19. Epigenetics in diagnosis, prognosis and therapy: therapies targeting the epigenome
	Introduction
	Types of epigenetic mechanisms
	Epigenetics in diagnosis
	Role of epigenetics in various diseases
	Epigenetics in cancer: toward simplified therapies
	Epigenetic treatments: reprogrammers & targeted therapy
	Epigenetic regulation of autophagy in cancer: a new approach to curb cancer?
	Future perspective & conclusion
	Acknowledgments
	References
Index
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