Impact of Endocrine Disruptors upon Non-Genetic Inheritance

Abstract

Similar to environmental factors, EDCs (endocrine-disrupting chemicals) can influence gene expression without modifying the DNA sequence. It is commonly accepted that the transgenerational inheritance of parentally acquired traits is conveyed by epigenetic alterations also known as "epimutations". DNA methylation, acetylation, histone modification, RNA-mediated effects and extracellular vesicle effects are the mechanisms that have been described so far to be responsible for these epimutations. They may lead to the transgenerational inheritance of diverse phenotypes in the progeny when they occur in the germ cells of an affected individual. While EDC-induced health effects have dramatically increased over the past decade, limited effects on sperm epigenetics have been described. However, there has been a gain of interest in this issue in recent years. The gametes (sperm and oocyte) represent targets for EDCs and thus a route for environmentally induced changes over several generations. This review aims at providing an overview of the epigenetic mechanisms that might be implicated in this transgenerational inheritance.

Keywords: embryo; endocrine-disrupting chemicals; epigenetics; non-genetic inheritance; oocyte; sperm; transgenerational inheritance.

Figure 1

Schematic representation of the diversity of inheritance players, without modification of the DNA sequence. They are involved in the modification of gene expression. These modifications include histone sumoylation, methylation, acetylation, ubiquitination, miRNA, DNA methylation, RNA methylation and other non-coding RNAs. miRNA may be transported by extracellular vesicles. When the gene promotor is targeted by epigenetic changes, it directly affects gene expression. Such epigenetic modifications may affect both spermatozoa and oocytes. (miRNA: microRNA, piRNA: piwi-interacting RNA, tRNA: transfer RNA, lncRNA: long non-coding RNA, mRNA: messenger RNA).

Figure 2

Schematic representation of the biogenesis and the diversity of extracellular vesicles (EVs). EVs are players in inheritance as they may transport diverse information to gametes and embryos.

Figure 3

Schematic DNA methylation dynamics occurring during germ cell specification and embryo development. During mammal development, two waves of global demethylation occur: after fertilization and before PGC differentiation. Each step depicted in this figure may be a target for EDC with an impact on the DNA methylation profile, which may in turn affect the health of subsequent generations. PGC: primordial germ cells.