State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Mol Cell Endocrinol. 2014 Feb 15;382(2):915-25. doi: 10.1016/j.mce.2013.11.007. Epub 2013 Nov 15.
Wnt signaling is an evolutionarily conserved pathway that regulates cell proliferation, differentiation and apoptosis. To investigate the possible role of Wnt signaling in the regulation of ovarian follicular development, secondary follicles were isolated and cultured in vitro in the presence or absence of its activator (LiCl or Wnt3a) or inhibitor (IWR-1). We have demonstrated that activation of β-catenin signals by activators dramatically suppressed follicular development by increasing granulosa cell apoptosis and inhibiting follicle steroidogenesis. In contrast, inhibition of Wnt signaling by IWR-1 was observed with better developed follicles and increased steroidogenesis. Further studies have shown that the transcription factor Forkhead box O3a (Foxo3a) and its downstream target molecules were modulated by the activators or the inhibitor. These findings provide evidence that Wnt signaling might negatively regulate follicular development potentially through Foxo3a signaling components.
Wnt 信号通路是一条进化上保守的通路，它调节细胞的增殖、分化和凋亡。为了研究 Wnt 信号通路在调节卵巢卵泡发育中的可能作用，我们分离并在体外培养次级卵泡，同时存在或不存在其激活剂（LiCl 或 Wnt3a）或抑制剂（IWR-1）。我们已经证明，激活剂通过激活 β-连环蛋白信号，通过增加颗粒细胞凋亡和抑制卵泡类固醇生成，显著抑制卵泡发育。相比之下，通过 IWR-1 抑制 Wnt 信号，观察到卵泡发育更好，类固醇生成增加。进一步的研究表明，转录因子叉头框蛋白 O3a（Foxo3a）及其下游靶分子被激活剂或抑制剂调节。这些发现提供了证据，表明 Wnt 信号通路可能通过 Foxo3a 信号通路成分负调节卵泡发育。
