slc38a9调控卵子成熟的功能与机制研究

卵子成熟障碍是女性不孕症的主要原因之一，鉴定调控卵子成熟的关键基因并揭示其分子机制具有重要的基础和临床意义。前期工作中我们发现一个雌性不育的斑马鱼突变体ja015，该突变体卵子成熟出现障碍，导致卵子无法受精，最终出现性逆转。更有趣的是我们发现调控卵细胞发育的重要基因转录本部分位于突变体卵细胞核内。我们鉴定出ja015突变体致变基因为slc38a9，检测出slc38a9在卵细胞中特异表达，并发现slc38a9突变导致卵细胞凋亡增多，mTORC1信号通路下调。为了阐明slc38a9调控卵子成熟的功能和机制，本项目将开展以下三项工作：1）具有卵子成熟障碍的ja015突变体的表型分析；2）突变体基因的定位克隆和确定；3）slc38a9通过介导mTORC1信号通路调控卵子成熟分子机制研究。本项目从分子，细胞水平揭示slc38a9调控卵子成熟的功能和机制，研究成果有利于深入理解卵子成熟的分子调控机制。

Oocytes maturation disorder is the major causes of female infertility. Identification of the key genes regulating oocyte maturation and revealing their molecular mechanisms have important basic and clinical significance. In the previous work, we found a infertile female zebrafish mutant ja015, which had an impaired maturity of oocytes and eventually reverted into the sterile males. More interestingly, we found that important gene transcripts that regulate oocyte development were located in the nucleus of oocytes. We identified the ja015 mutant gene as slc38a9, and detected the specific expression of slc38a9 in oocytes.In addition, we found that slc38a9 mutation resulted in increased apoptosis of oocytes and down-regulation of mTORC1 signaling. In order to elucidate the function and mechanism of slc38a9 regulating oocyte maturation, our work is divided into three parts: 1) Phenotypic analysis of ja015 mutant with oocyte maturation disorder; 2) Positional cloning and determination of mutant gene; 3) The molecular mechanisms of slc38a9 in regulating oocyte maturation by mediating mTORC1 signaling.Thus, our study will generate new knowledge on molecular mechanisms of oocyte maturation.