Zhang Guo-Liang, Sun Xiao-Feng, Feng Yan-Zhong, Li Bo, Li Ya-Peng, Yang Fan, Nyachoti Charles Martin, Shen Wei, Sun Shi-Duo, Li Lan
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong 266109, China.
Toxicol Appl Pharmacol. 2017 Feb 15;317:33-40. doi: 10.1016/j.taap.2017.01.004. Epub 2017 Jan 12.
Zearalenone (ZEA) is an estrogenic mycotoxin mainly produced as a secondary metabolite by numerous species of Fusarium. Previous work showed that ZEA had a negative impact on domestic animals with regard to reproduction. The adverse effects and the mechanisms of ZEA on mammalian ovarian folliculogenesis remain largely unknown, particularly its effect on primordial follicle formation. Thus, we investigated the biological effects of ZEA exposure on murine ovarian germ cell cyst breakdown and primordial follicle assembly. Our results demonstrated that newborn mouse ovaries exposed to 10 or 30μM ZEA in vitro had significantly less germ cell numbers compared to the control group. Moreover, the presence of ZEA in vitro increased the numbers of TUNEL and γH2AX positive cells within mouse ovaries and the ratio of mRNA levels of the apoptotic genes Bax/Bcl-2. Furthermore, ZEA exposure reduced the mRNA of oocyte specific genes such as LIM homeobox 8 (Lhx8), newborn ovary homeobox (Nobox), spermatogenesis and oogenesis helix-loop-helix (Sohlh2), and factor in the germline alpha (Figlα) in a dose dependent manner. Exposure to ZEA led to remarkable changes in the Lhx8 3'-UTR DNA methylation dynamics in oocytes and severely impaired folliculogenesis in ovaries after transplantation under the kidney capsules of immunodeficient mice. In conclusion, ZEA exposure impairs mouse primordial follicle formation in vitro.
玉米赤霉烯酮（ZEA）是一种具有雌激素活性的霉菌毒素，主要由多种镰刀菌作为次生代谢产物产生。先前的研究表明，ZEA对家畜的繁殖有负面影响。ZEA对哺乳动物卵巢卵泡发生的不良影响及其机制仍 largely unknown，尤其是其对原始卵泡形成的影响。因此，我们研究了ZEA暴露对小鼠卵巢生殖细胞囊肿破裂和原始卵泡组装的生物学效应。我们的结果表明，与对照组相比，体外暴露于10或30μM ZEA的新生小鼠卵巢中的生殖细胞数量显著减少。此外，体外ZEA的存在增加了小鼠卵巢中TUNEL和γH2AX阳性细胞的数量以及凋亡基因Bax/Bcl-2的mRNA水平比值。此外，ZEA暴露以剂量依赖的方式降低了卵母细胞特异性基因如LIM同源盒8（Lhx8）、新生卵巢同源盒（Nobox）、生精和卵子发生螺旋-环-螺旋（Sohlh2）以及生殖系α因子（Figlα）的mRNA水平。暴露于ZEA导致卵母细胞中Lhx8 3'-UTR DNA甲基化动力学发生显著变化，并在免疫缺陷小鼠肾囊下移植后严重损害卵巢中的卵泡发生。总之，ZEA暴露在体外损害小鼠原始卵泡的形成。
