Functional Analysis of SMAD Signaling in Oocytes

描述（由申请人提供）：卵母细胞-颗粒细胞交流在卵子发生过程中的重要性是公认的。tgf - β超家族的成员是卵母细胞-颗粒细胞通讯的重要介质，但这些配体对卵母细胞的直接作用尚不清楚。tgf - β配体通过磷酸化激活靶细胞中的SMAD蛋白。活化的smad （SMAD2/3和1/5/9）结合SMAD4并转运到细胞核，在那里它们调节细胞核功能。通过对Smad4基因在卵母细胞中无功能的突变动物的初步分析，本项目验证了以下假设：(1)卵母细胞中Smad4缺失导致卵泡发育增加；(2)Smad4突变卵母细胞比对照卵母细胞更具生物活性。总之，这两个目标的结果将为影响卵母细胞发育的机制提供有价值的见解，并可能允许开发改善卵母细胞质量和卵巢功能的干预措施。

DESCRIPTION (provided by applicant): The importance of oocyte-granulosa cell communication throughout oogenesis is well accepted. Members of the TGF-beta superfamily are important mediators of oocyte-granulosa cell communication, but the direct effect of these ligands on the oocyte is unclear. TGF-beta ligands activate SMAD proteins in target cells through phosphorylation. Activated SMADs (SMAD2/3 and 1/5/9) bind SMAD4 and translocate to the nucleus where they regulate nuclear functions. Based on preliminary analysis of mutant animals were the Smad4 gene is non-functional in oocytes, the present project tests the hypotheses that (1) Smad4 deletion in oocytes causes increased follicular development and (2) Smad4 mutant oocytes are more bioactive than control oocytes. Together, results from these two aims will provide valuable insight into mechanisms that affect oocyte development and may allow for development of interventions to improve oocyte quality and ovarian function. PUBLIC HEALTH RELEVANCE: The proposed research activities will increase our understanding of ovarian function, follicular and oocyte development. This knowledge will improve our ability to treat problems associated with defects in female reproduction, including infertility, premature ovarian failure and irregular menstrual cycles.