Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring
Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring
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父亲在生命早期暴露的 BPA 会改变精子中 Igf2 表观遗传状态并诱发大鼠后代的胰腺损伤
DOI：
10.1016/j.toxlet.2015.08.009
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发表时间：
2015-11-04
影响因子：
3.5
通讯作者：
Xu, Shunqing
中科院分区：
文献类型：
--
作者：
Mao, Zhenxing;Xia, Wei;Xu, Shunqing
在子宫内接触内分泌干扰物似乎会改变雄性种系的表观遗传学，并随后促进后代的成年发病。胎儿接触双酚 A (BPA)（环境中一种非常普遍的内分泌干扰物）已被证明会改变表观遗传修饰，并导致成年后出现葡萄糖不耐受。然而，胎儿接触 BPA 是否会引起其后代的表观遗传修饰和表型变化仍不清楚。本研究旨在调查生命早期接触 BPA 是否会通过雄性种系诱发后代葡萄糖不耐症，以及潜在的表观遗传分子基础。 F0妊娠SD大鼠在妊娠和哺乳期间接受玉米油或40μg/kg/天的BPA。 F1 雄性大鼠通过与未治疗的雌性大鼠交配来维持产生 F2 后代。断奶后的F1大鼠和F2后代均未接受任何其他治疗。我们的结果表明，BPA 组的雄性 F2 后代表现出葡萄糖不耐受和 β 细胞功能障碍。在雄性 F2 后代的胰岛中观察到 Igf2 表达降低和相关的 Igf2 甲基化。此外，在雌性 F2 动物中也观察到了类似的效果，但该效果在雄性动物中更为明显。此外，在成年F1雄性大鼠的精子中观察到Igf2的异常表达和甲基化，表明生殖细胞的表观遗传修饰可以部分进展到下一代。总体而言，我们的研究表明，生命早期接触 BPA 可能会导致后代通过雄性生殖系遗传葡萄糖耐受不良和 β 细胞功能障碍，这与胰岛中 Igf2 的高甲基化有关。生殖细胞表观遗传学的变化可能有助于这种代际传递。 (C) 2015 Elsevier Ireland Ltd. 保留所有权利。
Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 mu g/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and beta-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and beta-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission. (C) 2015 Elsevier Ireland Ltd. All rights reserved.