Laboratory of Germ Cell Biology, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China.
Environ Mol Mutagen. 2014 May;55(4):343-53. doi: 10.1002/em.21847. Epub 2014 Jan 24.
Bisphenol-A (BPA) and diethylhexyl phthalate (DEHP) are estrogenic compounds widely used in commercial plastic products. Previous studies have shown that exposure to such compounds have adverse effects on various aspects of mammalian reproduction including folliculogenesis. The objective of this study was to examine the effects of BPA and DEHP exposure on primordial follicle formation. We found that germ cell nest breakdown and primordial follicle assembly were significantly reduced when newborn mouse ovaries were exposed to 10 or 100 μM BPA and DEHP in vitro. Moreover, BPA and DEHP exposure increased the number of TUNEL positive oocytes and the mRNA level of the pro-apoptotic gene Bax in oocytes. These effects were associated with decreased expression of oocyte specific genes such as LIM homeobox 8 (Lhx8), factor in the germline alpha (Figla), spermatogenesis and oogenesis helix-loop-helix (Sohlh2), and newborn ovary homeobox (Nobox). Interestingly, BPA and DEHP exposure also prevented DNA demethylation of CpG sites of the Lhx8 gene in oocytes, a process normally associated with folliculogenesis. Finally, folliculogenesis was severely impaired in BPA and DEHP exposed ovaries after transplantation into the kidney capsules of immunodeficient mice. In conclusion, BPA and DEHP exposures impair mouse primordial follicle assembly in vitro.
双酚 A（BPA）和邻苯二甲酸二（2-乙基）己酯（DEHP）是广泛用于商业塑料产品的雌激素化合物。先前的研究表明，暴露于此类化合物会对哺乳动物生殖的各个方面产生不利影响，包括卵泡发生。本研究的目的是研究 BPA 和 DEHP 暴露对原始卵泡形成的影响。我们发现，当新生小鼠卵巢在体外暴露于 10 或 100 μM BPA 和 DEHP 时，生殖细胞巢破裂和原始卵泡组装明显减少。此外，BPA 和 DEHP 暴露增加了 TUNEL 阳性卵母细胞的数量和卵母细胞中促凋亡基因 Bax 的 mRNA 水平。这些作用与卵母细胞特异性基因如 LIM 同源盒 8（Lhx8）、生殖系α因子（Figla）、精子发生和卵母细胞螺旋环螺旋（Sohlh2）和新生卵巢同源盒（Nobox）的表达减少有关。有趣的是，BPA 和 DEHP 暴露还阻止了卵母细胞中 Lhx8 基因 CpG 位点的 DNA 去甲基化，这是一个通常与卵泡发生相关的过程。最后，BPA 和 DEHP 暴露后的卵泡发生在免疫缺陷小鼠的肾囊移植后严重受损。总之，BPA 和 DEHP 暴露会损害体外小鼠原始卵泡的组装。
