Estrogen Receptor-Related DNA and Histone Methylation May Be Involved in the Transgenerational Disruption in Spermatogenesis by Selective Toxic Chemicals

Xiao Han; Pengfei Zhang; Wei Shen; Yong Zhao; Hongfu Zhang

doi:10.3389/fphar.2019.01012

Estrogen Receptor-Related DNA and Histone Methylation May Be Involved in the Transgenerational Disruption in Spermatogenesis by Selective Toxic Chemicals

Front Pharmacol. 2019 Sep 11:10:1012. doi: 10.3389/fphar.2019.01012. eCollection 2019.

Authors

Xiao Han^{1

2}, Pengfei Zhang², Wei Shen², Yong Zhao^{2

3}, Hongfu Zhang³

Affiliations

¹ College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China.
² College of Life Sciences, Qingdao Agricultural University, Qingdao, China.
³ State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

Abstract

Air pollution is a global threat to human health especially spermatogenesis. Animal and epidemiological studies suggest that epigenetic factors can transmit the pathologies transgenerationally. Paternal epigenetic effects can greatly impact offspring health. In this study and together with our previous report, we found that H₂S donor Na₂S and/or NH₃ donor NH₄Cl diminished mouse fertility, decreased spermatozoa concentration and motility, and impaired spermatogenesis in three consequent generations (F0, F1, and F2). In the current study, we found that DNA methylation, histone methylation, and estrogen receptor alpha (ERα) were impaired by NH₄Cl and/or Na₂S in F0, F1, and F2 mouse testes. Moreover, NH₄Cl and/or Na₂S might act as environmental endocrine-disrupting chemicals to decrease estrogen and testosterone in mouse blood. It has been reported that ERα signaling is intertwined together with DNA methylation and histone methylation, which plays very important roles in spermatogenesis. These data together indicate that the transgenerational disruption in spermatogenesis by NH₄Cl and/or Na₂S may be through ERα-related DNA methylation and histone methylation pathways. Therefore, we strongly recommend that greater attention should be paid to NH₃ and/or H₂S contamination to minimize their impact on human health especially spermatogenesis.

Keywords: DNA methylation; H2S; NH3; estrogen signaling; histone methylation; spermatogenesis; transgenerational.