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首页> 外文期刊>Development >Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a.
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Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a.

机译:Foxo3a卵母细胞特异性表达的小鼠卵泡发育受阻所致的不育症。

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摘要

In recent years, mammalian oocytes have been proposed to have important roles in the orchestration of ovarian follicular development and fertility. To determine whether intra-oocyte Foxo3a, a component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, influences follicular development and female fertility, a transgenic mouse model was generated with constitutively active Foxo3a expressed in oocytes. We found that the female transgenic mice were infertile, which was caused by retarded oocyte growth and follicular development, and anovulation. Further mechanistic studies revealed that the constitutively active Foxo3a in oocytes caused a dramatic reduction in the expression of bone morphogenic protein 15 (Bmp15), connexin 37 and connexin 43, which are important molecules for the establishment of paracrine and gap junction communications in follicles. Foxo3a was also found to facilitate the nuclear localization of p27(kip1) in oocytes, a cyclin-dependent kinase (Cdk) inhibitor that may serve to inhibit oocyte growth. The results from the current study indicate that Foxo3a is an important intra-oocyte signaling molecule that negatively regulates oocyte growth and follicular development. Our study may therefore give some insight into oocyte-borne genetic aberrations that cause defects in follicular development and anovulation in human diseases, such as premature ovarian failure.
机译:近年来,已经提出哺乳动物卵母细胞在协调卵泡发育和生育能力中具有重要作用。为了确定卵母细胞内的Foxo3a是磷脂酰肌醇3激酶(PI3K)信号通路的组成部分,是否影响卵泡发育和女性生育能力,生成了在卵母细胞中具有组成型活性Foxo3a的转基因小鼠模型。我们发现雌性转基因小鼠不育,这是由于卵母细胞生长迟缓和卵泡发育以及无排卵引起的。进一步的机理研究表明,卵母细胞中的组成型活性Foxo3a导致骨形态发生蛋白15(Bmp15),连接蛋白37和连接蛋白43的表达急剧降低,这是在卵泡中建立旁分泌和间隙连接通讯的重要分子。还发现Foxo3a促进了卵母细胞中p27(kip1)的核定位,这是一种可抑制卵母细胞生长的细胞周期蛋白依赖性激酶(Cdk)抑制剂。当前研究的结果表明,Foxo3a是一种重要的卵母细胞内信号分子,它负调控卵母细胞的生长和卵泡发育。因此,我们的研究可能会深入了解卵母细胞传播的遗传畸变,这些畸变会导致卵泡发育和人类疾病(例如卵巢早衰)无排卵。

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