Li Mo, Ai Jun-Shu, Xu Bao-Zeng, Xiong Bo, Yin Shen, Lin Sheng-Li, Hou Yi, Chen Da-Yuan, Schatten Heide, Sun Qing-Yuan
State Key Laboratory of Reproductive Biology, Institute of Zoology, and Graduate School, Chinese Academy of Sciences, Beijing 100101, China.
Biol Reprod. 2008 Nov;79(5):897-905. doi: 10.1095/biolreprod.108.069245. Epub 2008 Jul 30.
The role of androgen and androgen receptors (ARs) in males has been well established. This steroid and its receptor also exist in follicles, but their functions are still unclear. In this study, using a culture system containing a low dose of hypoxanthine, we revealed the positive contribution of testosterone to oocyte meiotic resumption. By performing ultracentrifugation to allow clear visualization of porcine germinal vesicles, our results provide evidence that mitogen-activated protein kinase (MAPK) in the oocyte itself but not in cumulus cells was activated before germinal vesicle breakdown (GVBD) after testosterone treatment. We further explored the signal cascade of testosterone-triggered GVBD and showed significant contributions of AR to testosterone-induced MAPK activation and GVBD. By using a potent and selective inhibitor of SRC and detecting activation of the kinase, we found that testosterone activated SRC in oocytes but not in cumulus cells and that SRC (as an essential upstream molecule of MAPK) mediated this testosterone- and AR-promoted reinitiation of meiosis. The present findings propose an undefined signaling pathway and suggest the potential competence of testosterone for meiotic resumption in mammalian oocytes.
雄激素和雄激素受体（ARs）在雄性中的作用已得到充分证实。这种类固醇及其受体也存在于卵泡中，但其功能仍不清楚。在本研究中，我们使用含有低剂量次黄嘌呤的培养系统，揭示了睾酮对卵母细胞减数分裂恢复的积极作用。通过进行超速离心以使猪生发泡清晰可见，我们的结果提供了证据，表明在睾酮处理后，生发泡破裂（GVBD）之前，卵母细胞本身而非卵丘细胞中的丝裂原活化蛋白激酶（MAPK）被激活。我们进一步探究了睾酮触发GVBD的信号级联反应，并表明AR对睾酮诱导的MAPK激活和GVBD有显著作用。通过使用一种有效的、选择性的SRC抑制剂并检测该激酶的激活情况，我们发现睾酮在卵母细胞中而非卵丘细胞中激活了SRC，并且SRC（作为MAPK的重要上游分子）介导了这种睾酮和AR促进的减数分裂重新启动。目前的研究结果提出了一条未知的信号通路，并表明睾酮在哺乳动物卵母细胞减数分裂恢复方面具有潜在能力。
