G protein-coupled estrogen receptor signaling dependent epidermal growth-like factor expression is required for NPR2 inhibition and meiotic resumption in goat oocytes
G protein-coupled estrogen receptor signaling dependent epidermal growth-like factor expression is required for NPR2 inhibition and meiotic resumption in goat oocytes
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G 蛋白偶联雌激素受体信号传导依赖的表皮生长样因子表达是山羊卵母细胞中 NPR2 抑制和减数分裂恢复所必需的
DOI：
10.1016/j.theriogenology.2021.09.010
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发表时间：
2021-09-24
期刊：
影响因子：
2.8
通讯作者：
Ma, Baohua
中科院分区：
文献类型：
--
作者：
Lu, Sihai;Zhang, Hui;Ma, Baohua
G蛋白偶联雌激素受体（GPER）不同于传统的雌激素核受体（ER），它介导细胞内非基因组信号的快速转导，通过调节转录和细胞内第二信使发挥作用。研究表明GPER可能调控卵母细胞的成熟，但相关机制尚不完全清楚。本研究以山羊卵丘-卵母细胞复合体（COCs）为模型，探讨GPER对卵母细胞成熟的调控作用及其机制。我们的研究表明，17 β-雌二醇（E-2）显着减少环磷酸鸟苷（cGMP）的COCs的合成，并通过GPER加速山羊卵母细胞减数分裂的恢复。进一步研究发现，GPER可介导E-2下调山羊卵丘细胞中利钠肽受体2（NPR 2）蛋白的表达。此外，我们还发现E-2通过GPER显著上调山羊卵丘细胞表皮生长因子（EGF）样因子的mRNA水平，并激活下游EGF受体（EGFR）和细胞外信号调节激酶1/2（ERK 1/2）信号通路。AG 1478（EGFR抑制剂）和U 0126（ERK 1/2抑制剂）均能消除E-2对NPR 2蛋白表达的抑制作用。这些结果表明，E-2通过GPER上调山羊卵丘细胞EGF样因子的mRNA水平，激活下游EGF信号网络，抑制NPR 2蛋白的表达，从而导致山羊卵母细胞cGMP合成减少，加速减数分裂恢复。(c)2021年由Elsevier Inc.出版
G protein-coupled estrogen receptor (GPER), which is different from traditional estrogen nuclear receptors (ERs), mediates the rapid transduction of nongenomic signals in cells, and works by regulating transcription and intracellular second messengers. Studies have shown that GPER may regulate oocyte maturation, but the relevant mechanism is not entirely clear. Here, goat cumulus-oocyte complexes (COCs) were used as a model to explore the regulation and mechanism of GPER on oocyte maturation. Our study showed that 17 beta-estradiol (E-2) significantly reduced cyclic guanosine monophosphate (cGMP) synthesis in COCs and accelerated the meiotic resumption of goat oocytes via GPER. Further investigation found that GPER mediated the downregulation of natriuretic peptide receptor 2 (NPR2) protein expression in goat cumulus cells by E-2. In addition, we found that E-2 significantly upregulated the mRNA levels of epidermal growth (EGF)-like factors in goat cumulus cells through GPER, and activated the downstream EGF receptor (EGFR) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways. Both AG1478 (EGFR inhibitor) and U0126 (ERK1/2 inhibitor) abolished the inhibitory effect of E-2 on the protein expression of NPR2. These results indicate that, through GPER, E-2 upregulates the mRNA levels of EGF-like factors in goat cumulus cells and activates the downstream EGF signaling network to suppress the expression of NPR2 protein, which results in a decrease in cGMP synthesis and acceleration of meiotic resumption in goat oocytes. (c) 2021 Published by Elsevier Inc.