Transgenerational epigenetic imprinting of the male germline by endocrine disruptor exposure during gonadal sex determination (Retracted article. See vol. 150, pg. 2976, 2009)
Transgenerational epigenetic imprinting of the male germline by endocrine disruptor exposure during gonadal sex determination (Retracted article. See vol. 150, pg. 2976, 2009)
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DOI：
10.1210/en.2006-0987
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发表时间：
2006-12-01
期刊：
影响因子：
4.8
通讯作者：
Skinner, Michael K.
中科院分区：
文献类型：
--
作者：
Chang, Hung-Shu;Anway, Matthew D.;Skinner, Michael K.
以前发现，在性腺性别决定的时候，胚胎暴露于内分泌干扰物乙烯氯唑啉会促进跨代疾病状态。乙烯唑啉的作用似乎是由于雄性生殖系中的表观遗传改变传递给后代。对雄性生殖系（即精子）的跨代表观遗传效应的分析确定了25个候选DNA序列，这些序列在乙烯唑啉代精子中具有改变的甲基化模式。这些序列被鉴定并映射到特定的基因和非编码DNA区域。使用亚硫酸氢盐测序来确认15个候选DNA序列的改变的甲基化模式。在F2和F3代生殖系中发现这些基因/DNA序列的表观遗传模式（即甲基化）的改变。因此，雄性生殖系的重编程涉及诱导新的印记样基因/DNA序列，其获得至少通过父系等位基因传递的表观永久DNA甲基化模式。在胚胎发育过程中的几个基因的表达模式被发现在乙烯唑啉F-1和F2代睾丸改变。鉴定的许多印记样基因/DNA序列与表观遗传连锁疾病相关。总之，发现胚胎性腺性别决定期间内分泌干扰物暴露可促进雄性生殖系表观遗传（即诱导印记样基因/DNA序列）编程的改变，这与跨代疾病状态的发展有关。
Embryonic exposure to the endocrine disruptor vinclozolin at the time of gonadal sex determination was previously found to promote transgenerational disease states. The actions of vinclozolin appear to be due to epigenetic alterations in the male germline that are transmitted to subsequent generations. Analysis of the transgenerational epigenetic effects on the male germline (i.e. sperm) identified 25 candidate DNA sequences with altered methylation patterns in the vinclozolin generation sperm. These sequences were identified and mapped to specific genes and noncoding DNA regions. Bisulfite sequencing was used to confirm the altered methylation pattern of 15 of the candidate DNA sequences. Alterations in the epigenetic pattern (i.e. methylation) of these genes/DNA sequences were found in the F2 and F3 generation germline. Therefore, the reprogramming of the male germline involves the induction of new imprinted-like genes/DNA sequences that acquire an apparent permanent DNA methylation pattern that is passed at least through the paternal allele. The expression pattern of several of the genes during embryonic development were found to be altered in the vinclozolin F-1 and F2 generation testis. A number of the imprinted-like genes/DNA sequences identified are associated with epigenetic linked diseases. In summary, an endocrine disruptor exposure during embryonic gonadal sex determination was found to promote an alteration in the epigenetic ( i.e. induction of imprinted-like genes/DNA sequences) programming of the male germline, and this is associated with the development of transgenerational disease states.