Transgenerational male reproductive effect of prenatal arsenic exposure: abnormal spermatogenesis with Igf2/H19 epigenetic alteration in CD1 mouse
Guoying Yin, Liting Xia, Yaxing Hou, Yaoyan Li, Deqing Cao, Yanan Liu, Jingshan Chen, Juan Liu, Liwen Zhang, Qiaoyun Yang, Qiang Zhang, Naijun Tang
Abstract
Developmental exposure to environmental toxicants can induce transgenerational reproductive disease phenotypes through epigenetic mechanisms. We treated pregnant CD-1 (F0) mice with drinking water containing sodium arsenite (85 ppm) from days 8 to 18 of gestation. Male offspring were bred with untreated female mice until the F3 generation was produced. Our results revealed that F0 transient exposure to arsenic can cause decreased sperm quality and histological abnormalities in the F1 and F3. The overall methylation status of Igf2 DMR2 and H19 DMR was significantly lower in the arsenic-exposed group than that of the control group in both F1 and F3. The relative mRNA expression levels of Igf2 and H19 in arsenic-exposed males were significantly increased in both F1 and F3. This study indicates that ancestral exposure to arsenic may result in transgenerational inheritance of an impaired spermatogenesis phenotyping involving both epigenetic alterations and the abnormal expression of Igf2 and H19.