Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.
Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.
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DOI：
10.1016/j.reprotox.2012.09.005
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Skinner MK
中科院分区：
文献类型：
--
作者：
Guerrero-Bosagna C;Covert TR;Haque MM;Settles M;Nilsson EE;Anway MD;Skinner MK
内分泌干扰物乙烯菌核利林先前已被证明可促进大鼠成年发病疾病的表观遗传跨代遗传。目前的研究旨在研究乙烯菌核利林对小鼠的跨代作用。 F0代妊娠雌性在性腺性别决定过程中的短暂暴露促进了F3代雄性和雌性小鼠的跨代成年发病，包括生精细胞缺陷、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% 的乙烯菌核动物谱系动物患有疾病，其中 34% 的动物患有两种或多种不同的疾病状态。有趣的是，在远交 CD-1 品系中观察到了乙烯菌核诱导的跨代疾病，但在近交 129 小鼠品系中却没有观察到。对 F3 代精子表观基因组的分析确定了差异 DNA 甲基化区域，这些区域有可能用作跨代接触和疾病的表观遗传生物标志物。
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.
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