Estrogen receptor signaling alters sperm DNA methylation landscape in adult male rats

The aim of this study is to evaluate the effect of activation of estrogen signaling through the estrogen receptors (ER-alpha and ER-beta) on the sperm DNA methylome in adult rats. In vivo model for ER-alpha and ER-beta signaling activation were established using ER-alpha agonist 4,4',4''-(4-Propyl-[1H] pyrazole-1,3,5-triyl) (PPT), and ER-beta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), respectively. Adult male rats were given subcutaneous injections of either PPT or DPN for 60 days. Animals in the control group were administered vehicle control. To study the effects of estrogen activation on sperm DNA methylome Whole Genome-Bisulfite Sequencing (WGBS) in DNA extracted from caudal sperm was performed. DNA extracted from 3 animals were pooled in each group. This study highlights the role of ERs in shaping the sperm epigenome and that aberrant estrogen signaling could be a contributing factor in clinical conditions of male infertility.