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.

摘要

发育暴露于环境毒物可以通过表观遗传机制诱导跨代生殖疾病表型。我们从妊娠第 8 天到第 18 天用含有亚砷酸钠 (85 ppm) 的饮用水处理怀孕的 CD-1 (F0) 小鼠。雄性后代与未经处理的雌性小鼠一起繁殖，直到产生 F3 代。我们的研究结果表明，F0 短暂接触砷会导致 F1 和 F3 精子质量下降和组织学异常。砷暴露组Igf2 DMR2和H19 DMR的总体甲基化状态在F1和F3中均显着低于对照组。Igf2和H19的相对mRNA表达水平在砷暴露的男性中，F1 和 F3 均显着增加。这项研究表明，祖先接触砷可能导致精子发生表型受损的跨代遗传，包括表观遗传改变和Igf2和H19的异常表达。