Epigenetic regulation of reproduction in human and in animal models

Authors: Samantha L Wilson, Mary Wallingford

Publication date: 2021/07/01

Journal: Molecular Human Reproduction

Volume: 27

Issue: 7

Pages: gaab041

Publisher: Oxford University Press

URL Link: Epigenetic regulation of reproduction in human and in animal models

Abstract: Historically, epigenetics has referred to chemical modifications made to DNA that regulate gene expression without changing DNA sequence. These modifications are mitotically heritable and are passed from parent cell to daughter cell. The definition of epigenetics has expanded to include not only modifications made to DNA but also post-translational modifications to histones and chromatin structure. In the reproduction field, epigenetic research has mostly focused around epigenetic reprogramming, genomic imprinting, epigenomic changes related to pathology, and more recently cell-type composition, and epigenetic aging. DNA methylation is the most extensively studied epigenetic mark, particularly in reproductive biology, but an expanding epigenetics toolkit has also begun to provide methods for understanding the roles of chromatin accessibility and histone modifications (Table I). New published work is available on chromatin accessibility relating to the placenta (Domcke et al., 2020) as well as reproductive tissue cancers as reviewed recently (Ramarao-Milne et al., 2021). There is still much to learn mechanistically about the integration of DNA methylation, histone modifications and chromatin accessibility in reproductive tissues.

It is of great interest to the reproductive health community to advance understanding of how the epigenetic modifications in gametes, embryos, placentae and associated tissues change in response to a myriad of conditions, such as assisted reproductive techniques (ART), pathology, stress, and paternal age. To study epigenetic changes that are associated with human health and disease, it is also important to establish a nuanced understanding of epigenetic variability that exists in healthy tissues and cells. Previous work by M.H.R. highlighted innovative studies in cell-type specific gene expression through the ‘Single cell analysis in development’ special issue. M.H.R. now aims to provide a unique resource to the reproduction field by publishing a special collection of reproductive epigenetics articles (Barratt, 2016) . Overall, a large knowledgebase has established that epigenetic regulation plays a critical role in developmental origins of health and disease (DoHaD) (Barker, 2007), but reproductive medicine has yet to develop ways to harness the potential that epigenetic mechanisms may have in the treatment of disease. Comparative study of human health and disease, animal models, and in vitro systems is crucial to support the investigation of hypothesized mechanisms of epigenetic regulation. To support the advancement of this field, M.H.R. is currently accepting original research and review articles in consideration of a special collection on reproductive epigenetics. A comprehensive, integrated understanding of tissue-specific and cell type-specific epigenetic mechanisms in normal, disease, and aging contexts is needed to provide building blocks for the development of new biomarkers and therapeutic approaches, such as those used in fertility preservation following chemotherapy (Szymanska et al., 2020). The M.H.R. ‘Human and Animal Model Reproductive Epigenetics’ collection will serve as a platform for discussion and collaboration by recognizing emerging innovative breakthroughs and significant accomplishments. In the sections below, we elaborate further on some of the specific focus areas that are of interest within the field of reproductive epigenetics.