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- Title
Epi-mutations for spermatogenic defects by maternal exposure to di(2-ethylhexyl) phthalate.
- Authors
Yukiko Tando; Hitoshi Hiura; Asuka Takehara; Yumi Ito-Matsuoka; Takahiro Arima; Yasuhisa Matsui
- 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 Hist1h2ba, Sycp1, and Taf7l, 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 Hist1h2ba, Sycp1, and Taf7l results in downregulation of these genes in spermatogonia and subsequent defects in spermatogenesis, at least in the F1 generation.
- Subjects
MATERNAL exposure; SPERMATOGENESIS; GERM cells; ENVIRONMENTAL exposure; FETAL development; GENE expression; PHTHALATE esters
- Publication
eLife, 2021, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.70322