Subfertility with defective folliculogenesis in female mice lacking testicular orphan nuclear receptor 4
Subfertility with defective folliculogenesis in female mice lacking testicular orphan nuclear receptor 4
复制标题
DOI：
10.1210/me.2007-0181
复制
发表时间：
2008-04-01
影响因子：
--
通讯作者：
Chang, Chawnshang
中科院分区：
文献类型：
--
作者：
Chen, Lu-Min;Wang, Ruey-Sheng;Chang, Chawnshang
睾丸孤儿核受体4(TR4)对雄性小鼠正常的精子发生起着重要的作用。然而，它在女性生育和卵巢功能中的作用在很大程度上仍不清楚。在这里，我们发现缺乏TR4(TR4(-/-))的雌性小鼠表现出不育和不规则的发情周期。TR4(-/-)雌性小鼠卵巢较小，排卵前卵泡和黄体较少或没有。超数排卵后，TR4(-/-)雌性小鼠产生的卵母细胞、排卵前卵泡和黄体较少。此外，TR4(-/-)卵巢颗粒细胞凋亡率较高。功能分析表明，TR4(-/-)雌性小鼠的不育症可能是由于卵巢缺陷导致卵泡发育受损，而不是垂体促性腺激素缺乏。卵泡发生缺陷研究发现，TR4可能通过直接与其5‘端启动子结合来诱导促黄体生成素受体(LHR)基因表达。TR4(-/-)雌性小鼠LHR表达减少的结果可能会通过类固醇合成相关酶的表达减少而导致性激素减少。综上所述，我们的结果表明，TR4可能通过影响LHR信号而在正常卵泡发生中发挥重要作用。通过其上游信号或未知配体(S)调节TR4的表达和/或激活，可能会使我们开发出小分子(S)来控制卵泡发生。
Testicular orphan nuclear receptor 4 (TR4) plays essential roles for normal spermatogenesis in male mice. However, its roles in female fertility and ovarian function remain largely unknown. Here we found female mice lacking TR4 ( TR4 (-/-)) displayed subfertility and irregular estrous cycles. TR4 (-/-) female mice ovaries were smaller with fewer or no preovulatory follicles and corpora lutea. After superovulation, TR4 (-/-) female mice produced fewer oocytes, preovulatory follicles, and corpora lutea. In addition, more intensive granulosa apoptosis was found in TR4 (-/-) ovaries. Functional analyses suggest that subfertility in TR4 (-/-) female mice can be due to an ovarian defect with impaired folliculogenesis rather than a deficiency in pituitary gonadotropins. defective folliculogenesis found TR4 might induce LH receptor (LHR) gene expression via direct binding to its 5' promoter. The consequence of reduced LHR expression in TR4 (-/-) female mice might then result in reduced gonadal sex hormones via reduced expression of enzymes involved in steroidogenesis. Together, our results showed TR4 might play essential roles in normal folliculogenesis by influencing LHR signals. Modulation of TR4 expression and/ or activation via its upstream signals or unidentified ligand(s) might allow us to develop small molecule( s) to control folliculogenesis.