Developmental windows of susceptibility for epigenetic inheritance through the male germline

Ly, Lundi; Chan, Donovan; Trasler, Jacquetta M.

doi:10.1016/j.semcdb.2015.07.006

Cited by 84 publications

(81 citation statements)

References 101 publications

(147 reference statements)

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“…Developmental reprogramming is shown to be caused by alterations in the epigenome (2,13,14). Epigenetic modifications play an important role in ‘programming’ lineage determination and cellular identity during development (15).…”

Section: Developmental Reprogramming and Epigenetic Regulationmentioning

confidence: 99%

Developmental Exposure to Endocrine Disrupting Chemicals Alters the Epigenome: Identification of Reprogrammed Targets

Prusinski

Al-Hendy

Yang

2016

Gynecol Obstet Res Open J

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Endocrine disruptions induced by environmental toxicants have placed an immense burden on society to properly diagnose, treat and attempt to alleviate symptoms and disease. Environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life - a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly-regulated and precisely-timed molecular, biochemical and cellular events. Humans may encounter endocrine disrupting chemicals (EDCs) daily and during all stages of life, from conception and fetal development through adulthood and senescence. Though puberty and perimenopausal periods may be affected by endocrine disruption due to hormonal effects, prenatal and early postnatal windows are most critical for proper development due to rapid changes in system growth. Developmental reprogramming is shown to be caused by alterations in the epigenome. Development is the time when epigenetic programs are ‘installed’ on the genome by ‘writers’, such as histone methyltransferases (HMTs) and DNA methyltransferases (DNMTs), which add methyl groups to lysine and arginine residues on histone tails and to CpG sites in DNA, respectively. A number of environmental compounds, referred to as estrogenic endocrine disruptors (EEDs), are able to bind to estrogen receptors (ERs) and interfere with the normal cellular development in target tissues including the prostate and uterus. These EEDs, including diethylstilbestrol (DES), bisphenol A (BPA), and genistein (a phytoestrogen derived from soybeans), have been implicated in the malformation of reproductive organs and later development of disease. Due to the lack of fully understanding the underlying mechanisms of how environmental toxicants and their level of exposure affect the human genome, it can be challenging to create clear clinical guidance to address the potential health effects of lower-level exposures commonly experienced within the general population. In addition, human studies concerning environmental exposures are limited in feasibility by ethical concerns for human safety. Therefore, studies in animal models provide great opportunities to reveal links between early-life exposure to EDCs and related diseases. It has been shown that developmental exposure to EDCs, such as diethylstilbestrol (DES) and genistein, during reproductive tract development increases the incidence, multiplicity and overall size of uterine fibroids in the Eker rat model, concomitantly reprogramming estrogen-responsive gene expression. Importantly, EDC exposure represses enhancer of zeste 2 (EZH2) and reduces levels of the histone 3 lysine 27 trimethylation (H3K27me3) repressive mark through Estrogen receptor / Phosphatidylinositide 3-kinases / Protein kinase B non-genomic signaling in the developing uterus. More recent research identified a developmental reprogramming target, Scbg2a1 gene, whose epigen...

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Section: Developmental Reprogramming and Epigenetic Regulationmentioning

confidence: 99%

Developmental Exposure to Endocrine Disrupting Chemicals Alters the Epigenome: Identification of Reprogrammed Targets

Prusinski

Al-Hendy

Yang

2016

Gynecol Obstet Res Open J

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“…3) (Soubry et al 2014, Ly et al 2015. While the literature is most substantiated concerning the epigenetic reprogramming for mice gametogenesis, the overall mechanisms are relatively similar in humans.…”

Section: Epigenetic Reprogramming Escapees and Windows Of Susceptibimentioning

confidence: 99%

“…Since recent studies have shown that this is possible for some epigenetic alterations, the foundation for intergenerational and transgenerational epigenetic inheritance through the male germ line exists (Soubry et al 2014, Ly et al 2015. Studies have shown that the inheritable epigenetic marks are primarily associated with genes involved in CNS and metabolism, opening the possibility of the epigenetic inheritance of metabolic disturbances (Tang et al 2015, Donkin et al 2016.…”

Section: Perspectivesmentioning

confidence: 99%

DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line

Illum

Bak

Lund

et al. 2018

Journal of Molecular Endocrinology

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The global rise in metabolic diseases can be attributed to a complex interplay between biology, behavior and environmental factors. This article reviews the current literature concerning DNA methylation-based epigenetic inheritance (intergenerational and transgenerational) of metabolic diseases through the male germ line. Included are a presentation of the basic principles for DNA methylation in developmental programming, and a description of windows of susceptibility for the inheritance of environmentally induced aberrations in DNA methylation and their associated metabolic disease phenotypes. To this end, escapees, genomic regions with the intrinsic potential to transmit acquired paternal epigenetic information across generations by escaping the extensive programmed DNA demethylation that occurs during gametogenesis and in the zygote, are described. The ongoing descriptive and functional examinations of DNA methylation in the relevant biological samples, in conjugation with analyses of noncoding RNA and histone modifications, hold promise for improved delineation of the effect size and mechanistic background for epigenetic inheritance of metabolic diseases.

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“…It usually takes about 6 weeks to differentiate mature sperm from PGCs via prospermatogonia in vivo, whereas it requires only 2-3 weeks to progress from PGCLCs to haploid spermatid in culture (Zhou et al 2016), and thus, the latter process is unlikely to recapitulate faithfully gametogenesis in vivo. Similarity between in vivo and in vitro gametogenesis or so-called 'biological reproducibility', seems particularly important, as evidence shows that prospermatogonia undergo dynamic epigenetic rearrangement (Davis et al 2000, Ueda et al 2000, Ly et al 2015 and are likely sensitive to manipulation in culture , Ishikura et al 2016. Moreover, biological reproducibility is also an important criterion when evaluating whether a culture system can be used as a model that can replace experimental animals.…”

Section: Reconstitution Of the Male Germ Line: Direct Derivation Of Hmentioning

confidence: 99%

“…In the male gonad, on the other hand, PGCs are arrested at the G1 stage, and thereby become prospermatogonia. During the cell cycle arrest, the prospermatogonia acquire de novo epigenetic modifications (Davis et al 2000, Ueda et al 2000, Ly et al 2015. After birth, some of the prospermatogonia become spermatogonial stem cells (SSCs), which are crucial for sustaining spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

Stem cells, in vitro gametogenesis and male fertility

Nagamatsu

Hayashi

2017

Reproduction

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Reconstitution in culture of biological processes, such as differentiation and organization, is a key challenge in regenerative medicine, and one in which stem cell technology plays a central role. Pluripotent stem cells and spermatogonial stem cells are useful materials for reconstitution of germ cell development in vitro, as they are capable of differentiating into gametes. Reconstitution of germ cell development, termed in vitro gametogenesis, will provide an experimental platform for a better understanding of germ cell development, as well as an alternative source of gametes for reproduction, with the potential to cure infertility. Since germ cells are the cells for 'the next generation', both the culture system and its products must be carefully evaluated. In this issue, we summarize the progress in in vitro gametogenesis, most of which has been made using mouse models, as well as the future challenges in this field. Reproduction (2017) 154 F79-F91

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Developmental windows of susceptibility for epigenetic inheritance through the male germline

Cited by 84 publications

References 101 publications

Developmental Exposure to Endocrine Disrupting Chemicals Alters the Epigenome: Identification of Reprogrammed Targets

Developmental Exposure to Endocrine Disrupting Chemicals Alters the Epigenome: Identification of Reprogrammed Targets

DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line

Stem cells, in vitro gametogenesis and male fertility

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