Chlordecone (CD) is an insecticide that was used in the French West Indies for several years to control the banana root borer pest. Given its nonsignificant degradation, it persists in the environment. CD is a carcinogenic compound with reproductive and developmental toxicity and is a recognized endocrine-disrupting chemical. In this study, we examined the effects of CD on female reproductive system of mice with the focus on epigenetic features in ovary. Our data show that gestational exposure to low dose of CD affects meiotic double-strand breaks repair in female embryos. In adult mice derived from CD-treated pregnant females, we observed delayed puberty, decreased number of primordial and increased number of atretic follicles. Gene expression analysis revealed that Rcbtb2 and Rbpms genes were not expressed in embryonic gonads. Estrogen signaling- and oocyte maturation-associated genes were downregulated in adult ovaries. The morphological changes were associated with altered epigenetic features: increased H2Aub and increased H3K27me3 and decreased H4ac and H3K4me3 in embryonic oocytes. The DNA damage-associated, γH2AX marks were detected in the follicles of treated but not control adult ovaries. We also found reduced H3K4me3 and H4ac in fully grown oocytes of the treated ovaries. The ChIP-seq analysis of H3K4me3 in adult ovaries showed that target genes of ZFP57 and TRIM28, which regulate pluripotency and imprinting, were significantly enriched in altered regions. Our study clearly demonstrates that gestational exposure to a low dose of CD impairs the function of female reproductive system and the changes are associated with altered epigenetic features.

中文翻译：

---

产前接触杀虫剂十氯酮引起的卵巢功能异常与表观遗传学特征改变有关。

十氯酮（CD）是一种杀虫剂，在法属西印度群岛已使用了几年来控制香蕉根虫害虫。鉴于其无显着的降解，它可以在环境中持久存在。CD是具有生殖和发育毒性的致癌化合物，并且是公认的破坏内分泌的化学物质。在这项研究中，我们检查了CD对小鼠雌性生殖系统的影响，重点是卵巢的表观遗传特征。我们的数据表明，低剂量CD的妊娠暴露会影响雌性胚胎的减数分裂双链断裂修复。在从接受CD治疗的雌性小鼠中获得的成年小鼠中，我们观察到青春期延迟，原初数量减少和闭锁卵泡数量增加。基因表达分析表明，Rcbtb2和Rbpms基因在胚胎性腺中不表达。在成年卵巢中，雌激素信号转导和卵母细胞成熟相关基因被下调。形态变化与表观遗传特征的改变有关：胚胎卵母细胞中H2Aub的增加和H3K27me3的增加以及H4ac和H3K4me3的减少。在已治疗但未控制的成年卵巢的卵泡中检测到与DNA损伤相关的γH2AX标记。我们还发现，经治疗的卵巢完全生长的卵母细胞中的H3K4me3和H4ac减少。H3K4me3在成年卵巢中的ChIP-seq分析显示，调节多能性和印迹的ZFP57和TRIM28的靶基因在改变的区域中显着富集。我们的研究清楚地表明，低剂量CD的妊娠暴露会损害女性生殖系统的功能，并且这些变化与表观遗传特征的改变有关。