Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, United States.
Reprod Toxicol. 2012 Dec;34(4):694-707. doi: 10.1016/j.reprotox.2012.09.005. Epub 2012 Oct 2.
The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease.
内分泌干扰物 vinylzolin 先前已被证明可促进大鼠成年发病的表观遗传跨代遗传。本研究旨在研究 vinylzolin 对小鼠的跨代作用。在生殖性别决定期间短暂暴露 F0 代孕雌性可促进 F3 代雄性和雌性小鼠的成年发病，包括精子发生细胞缺陷、睾丸异常、前列腺异常、肾脏异常和多囊卵巢疾病。病理学分析表明，75%的 vinylzolin 系动物发生疾病，其中 34%有两种或更多不同的疾病状态。有趣的是，vinclozolin 诱导的跨代疾病发生在杂交 CD-1 品系中，但不在近交 129 小鼠品系中。对 F3 代精子表观基因组的分析确定了差异 DNA 甲基化区域，这些区域可潜在用作跨代暴露和疾病的表观遗传生物标志物。
