Estrogen receptors in granulosa cells govern meiotic resumption of pre-ovulatory oocytes in mammals.
Estrogen receptors in granulosa cells govern meiotic resumption of pre-ovulatory oocytes in mammals.
复制标题
颗粒细胞中的雌激素受体控制哺乳动物排卵前卵母细胞的减数分裂恢复。
DOI：
10.1038/cddis.2017.82
复制
发表时间：
2017-03-09
影响因子：
9
通讯作者：
Xia G
中科院分区：
文献类型：
--
作者：
Liu W;Xin Q;Wang X;Wang S;Wang H;Zhang W;Yang Y;Zhang Y;Zhang Z;Wang C;Xu Y;Duan E;Xia G
在哺乳动物中，卵母细胞在减数分裂 I 的双线期停滞，直到排卵前黄体生成素 (LH) 激增通过卵泡颗粒细胞中的信号触发减数分裂恢复。在这项研究中，我们表明卵泡颗粒细胞中的雌二醇（E2）-雌激素受体（ER）系统在控制哺乳动物卵母细胞减数分裂恢复中起主导作用。我们发现生理条件下ERs的表达受促性腺激素控制。 E2-ERs系统通过调节利钠肽C和利钠肽受体2（NPPC/NPR2）的表达来维持卵母细胞减数分裂停滞，这是通过直接结合Nppc和Npr2基因的启动子区域来实现的。在 ER 基因敲除小鼠中，体外大多数卵丘-卵母细胞复合体中 E2 未能维持减数分裂停滞，而体内排卵前卵泡中减数分裂则提前恢复。在人颗粒细胞中，也得出了类似的结论：ER 水平受促性腺激素控制，E2-ER 调节 NPPC/NPR2 水平的表达。此外，我们的结果表明，体内和体外促卵泡激素和 LH 对 ER 水平的不同调节模式决定了它们对卵母细胞成熟的不同作用。综上所述，这些发现表明 E2-ERs 系统在卵母细胞减数分裂过程中发挥着关键作用，并可能为临床实践中的卵母细胞体外成熟治疗提出一种新方法。
In mammals, oocytes are arrested at the diplotene stage of meiosis I until the pre-ovulatory luteinizing hormone (LH) surge triggers meiotic resumption through the signals in follicular granulosa cells. In this study, we show that the estradiol (E2)-estrogen receptors (ERs) system in follicular granulosa cells has a dominant role in controlling oocyte meiotic resumption in mammals. We found that the expression of ERs was controlled by gonadotropins under physiological conditions. E2-ERs system was functional in maintaining oocyte meiotic arrest by regulating the expression of natriuretic peptide C and natriuretic peptide receptor 2 (NPPC/NPR2), which was achieved through binding to the promoter regions of Nppc and Npr2 genes directly. In ER knockout mice, meiotic arrest was not sustained by E2 in most cumulus–oocyte complexes in vitro and meiosis resumed precociously in pre-ovulatory follicles in vivo. In human granulosa cells, similar conclusions are reached that ER levels were controlled by gonadotropins and E2-ERs regulated the expression of NPPC/NPR2 levels. In addition, our results revealed that the different regulating patterns of follicle-stimulating hormone and LH on ER levels in vivo versus in vitro determined their distinct actions on oocyte maturation. Taken together, these findings suggest a critical role of E2-ERs system during oocyte meiotic progression and may propose a novel approach for oocyte in vitro maturation treatment in clinical practice.