Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav), IPN 2508, Col. San Pedro Zacatenco, México City 07360, Mexico.
Departamento de Biociencias e Ingenieria CIIEMAD, del Instituto Politécnico Nacional, México City, Mexico.
Toxicol Appl Pharmacol. 2018 Apr 1;344:13-22. doi: 10.1016/j.taap.2018.02.011. Epub 2018 Feb 16.
In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC. Cumulus cell-oocyte complexes (COCs) isolated from mouse preovulatory follicles were cultured with 0, 0.22, 2.2, 22, 220, and 2200 nM BPA for 2 h. An additional 16-h incubation with epidermal growth factor (EGF) was performed to promote the occurrence of meiotic resumption and progression to metaphase II. Without EGF stimulus, BPA treatment increased the percentage of oocytes undergoing meiotic resumption, decreased GJIC in the COCs, and did not modify GJIC gene (Cx43 and Cx37) and protein (CX43) expression. Following EGF stimulus, BPA increased the percentage of oocytes that remained at the anaphase and telophase stages, and decreased the percentage of oocytes reaching the metaphase II stage. Concomitantly, BPA reduced the expansion of cumulus cells. Carbenoxolone (a GJIC inhibitor) and 6-diazo-5-oxo-l-norleucine (a cumulus cell-expansion inhibitor) exerted effects on meiotic division similar to those exerted by BPA. These data suggest that BPA accelerates meiotic progression, leading to impaired prophase I-to-metaphase II transition, and that this adverse effect is correlated with reduced bidirectional communication in the COC.
在卵巢卵泡中，卵丘细胞通过缝隙连接细胞间通讯 (GJIC) 与卵母细胞进行通讯，以滋养卵母细胞并控制其减数分裂阻滞和分裂。双酚 A (BPA) 是聚碳酸酯制成的容器中的一种单体，可引起功能改变，包括卵母细胞减数分裂受损和 GJIC 中分子转移减少。然而，BPA 如何改变卵母细胞的减数分裂尚不清楚。我们研究了 BPA 对卵母细胞减数分裂的影响是否与 GJIC 中转移减少有关。从小鼠排卵前卵泡中分离出卵丘细胞-卵母细胞复合体 (COC)，用 0、0.22、2.2、22、220 和 2200 nM BPA 培养 2 小时。然后进行 16 小时的表皮生长因子 (EGF) 孵育，以促进减数恢复和进展到中期 II 阶段。没有 EGF 刺激，BPA 处理增加了经历减数恢复的卵母细胞的百分比，降低了 COC 中的 GJIC，并且不改变 GJIC 基因 (Cx43 和 Cx37) 和蛋白 (CX43) 的表达。在 EGF 刺激后，BPA 增加了处于后期和末期的卵母细胞的百分比，并降低了达到中期 II 阶段的卵母细胞的百分比。同时，BPA 减少了卵丘细胞的扩张。白杨黄素 (GJIC 抑制剂) 和 6-二氮-5-氧-L-正亮氨酸 (卵丘细胞扩张抑制剂) 对减数分裂的作用与 BPA 相似。这些数据表明，BPA 加速减数分裂进程，导致前期 I 到中期 II 的转变受损，这种不利影响与 COC 中双向通讯减少有关。
