Epi-mutations for Spermatogenic Defects by Maternal Exposure to Di(2-ethylhexyl) Phthalate

Overview

Journal Elife

Specialty Biology

Date 2021 Jul 28

PMID 34319233

Citations 5

Authors

Yukiko Tando

Hitoshi Hiura

Asuka Takehara

Yumi Ito-Matsuoka

Takahiro Arima

Yasuhisa Matsui

Affiliations

Soon will be listed here.

Abstract

Exposure to environmental factors during fetal development may lead to epigenomic modifications in fetal germ cells, altering gene expression and promoting diseases in successive generations. In mouse, maternal exposure to di(2-ethylhexyl) phthalate (DEHP) is known to induce defects in spermatogenesis in successive generations, but the mechanism(s) of impaired spermatogenesis are unclear. Here, we showed that maternal DEHP exposure results in DNA hypermethylation of promoters of spermatogenesis-related genes in fetal testicular germ cells in F1 mice, and hypermethylation of , and , which are crucial for spermatogenesis, persisted from fetal testicular cells to adult spermatogonia, resulting in the downregulation of expression of these genes. Forced methylation of these gene promoters silenced expression of these loci in a reporter assay. These results suggested that maternal DEHP exposure-induced hypermethylation of , and results in downregulation of these genes in spermatogonia and subsequent defects in spermatogenesis, at least in the F1 generation.

Citing Articles

LARP7 is required for sex chromosome silencing during meiosis in mice.

Tando Y, Nonomura A, Ito-Matsuoka Y, Takehara A, Okamura D, Hayashi Y PLoS One. 2024; 19(12):e0314329.

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Inheritance of environment-induced phenotypic changes through epigenetic mechanisms.

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Identification of spermatogenesis-associated changes in DNA methylation induced by maternal exposure to chemicals in male germ cells.

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Impact of Endocrine Disruptors upon Non-Genetic Inheritance.

Montjean D, Neyroud A, Yefimova M, Benkhalifa M, Cabry R, Ravel C Int J Mol Sci. 2022; 23(6).

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