Epigenetic Analysis of neonatal diethylstilbestrol (DES) exposure: Whole-transcriptome expression and DNA methylation profiles of the adult mouse seminal vesicle (SV)

Authors

• Y Li
• KJ Hamilton
• T Wang
• L Liu
• K Gerrish
• PA Wade
• KS Korach

Abstract

Epigenetic mechanisms such as DNA methylation play important roles in our development and in various diseases. Diethylstilbestrol (DES) is a synthetic estrogen that is associated with adverse effects on reproductive organs. Previously, we demonstrate that DES-induced toxicity of the mouse seminal vesicle (SV) is mediated by estrogen receptor α (ERα) and alteration in expression of seminal vesicle secretory protein IV (Svs4) and lactoferrin (Ltf) genes associates with changes in DNA methylation. In this study, we profiled the whole transcriptome expression of the WT and αERKO adult mouse SVs. The results showed some variability within the groups but they appeared to cluster based on treatments. In the WT SVs, DES significantly altered over 2000 protein-coding genes and they were distributed throughout all chromosomes. However, those gene changes did not occur in the αERKO SVs after DES exposure, suggesting that changes of the genes are ERα dependent. When we compared the gene expression profiling of the mouse uterus, we found about 30% overlap of genes in the DES-exposure group between the male SVs and the female uterus tissues. In addition, we found that 1700 ERα-dependent non-coding RNAs, including 6 micro RNAs were altered by DES exposure. We also profiled whole-genome DNA methylation by MBDcapture ChIP-seq analysis. We conclude that DES-induced toxicity results from altered whole transcriptome expression and changes of the genes are mediated by ERα in the adult mouse SVs. These findings provide a new approach towards further understanding the mechanism during developmental exposure to endocrine-disrupting chemicals in the reproductive system.

Scientific Focus Area: Cancer Biology

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