Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong, Agricultural University, Wuhan, 430070, China.
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong, Agricultural University, Wuhan, 430070, China; Biochip Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, China.
Chemosphere. 2020 Jun;249:126182. doi: 10.1016/j.chemosphere.2020.126182. Epub 2020 Feb 11.
An adverse tendency induced by the environmental estrogens in female reproductive health is one serious problem worldwide. Diethylstilbestrol (DES), as a synthetic estrogen, is still used as an animal growth stimulant in terrestrial livestock and aquaculture illegally. It has been reported to negatively affect ovarian function and oogenesis. Nevertheless, the mechanism and toxicity of DES on oocyte meiotic maturation are largely unknown. Herein, we found that DES (40 μM) intervened in mouse oocyte maturation and first polar body extrusion (PBE) was decreased in vitro. Cell cycle analysis showed meiotic process was disturbed with oocytes arrested at metaphase I (MI) stage after DES exposure. Further study showed that DES exposure disrupted the spindle assembly and chromosome alignment, which then continuously provoke the spindle assemble checkpoint (SAC). We also observed that the acetylation levels of α-tubulin were dramatically increased in DES-treated oocytes. In addition, the dynamics of actin were also affected. Moreover, the distribution patterns of estrogen receptor α (ERα) were altered in DES-treated oocyte, as indicated by the significant signals accumulation in the spindle area. However, ERα inhibitor failed to rescue the defects of oocyte maturation caused by DES. Of note, the same phenomenon was observed in estrogen-treated oocytes. Collectively, we showed that DES exposure lead to the oocyte meiotic failure via impairing the spindle assembly and chromosome alignment. Our research is helpful to understand how environmental estrogen affects female germ cells and contribute to design the potential therapies to preserve fertility especially for occupational exposure.
环境雌激素对女性生殖健康的不良影响是一个全球性的严重问题。己烯雌酚（DES）作为一种合成雌激素，仍被非法用作陆地牲畜和水产养殖中的动物生长刺激剂。据报道，它会对卵巢功能和卵子发生产生负面影响。然而，DES 对卵母细胞减数分裂成熟的机制和毒性在很大程度上尚不清楚。在此，我们发现 DES（40 μM）干预了小鼠卵母细胞的成熟，体外第一极体挤出（PBE）减少。细胞周期分析显示减数分裂过程受到干扰，DES 暴露后卵母细胞停滞在第一次减数分裂中期（MI）阶段。进一步的研究表明，DES 暴露破坏了纺锤体的组装和染色体的排列，从而持续引发纺锤体装配检查点（SAC）。我们还观察到 DES 处理的卵母细胞中α-微管蛋白的乙酰化水平显著增加。此外，肌动蛋白的动力学也受到影响。此外，DES 处理的卵母细胞中雌激素受体α（ERα）的分布模式也发生了改变，表明纺锤体区域的信号积累明显。然而，ERα 抑制剂未能挽救 DES 引起的卵母细胞成熟缺陷。值得注意的是，在雌激素处理的卵母细胞中也观察到了相同的现象。总之，我们表明 DES 暴露通过破坏纺锤体的组装和染色体的排列导致卵母细胞减数分裂失败。我们的研究有助于了解环境雌激素如何影响女性生殖细胞，并有助于设计潜在的疗法来保护生育能力，特别是针对职业暴露。
