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首页> 外文期刊>Biology Open >RHAMM deficiency disrupts folliculogenesis resulting in female hypofertility
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RHAMM deficiency disrupts folliculogenesis resulting in female hypofertility

机译：RHAMM缺乏会破坏卵泡生成，导致女性生育力下降

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The postnatal mammalian ovary contains the primary follicles, each comprising an immature oocyte surrounded by a layer of somatic granulosa cells. Oocytes reach meiotic and developmental competence via folliculogenesis. During this process, the granulosa cells proliferate massively around the oocyte, form an extensive extracellular matrix (ECM) and differentiate into cumulus cells. As the ECM component hyaluronic acid (HA) is thought to form the backbone of the oocyte-granulosa cell complex, we deleted the relevant domain of the Receptor for HA Mediated Motility (RHAMM) gene in the mouse. This resulted in folliculogenesis defects and female hypofertility, although HA-induced signalling was not affected. We report that wild-type RHAMM localises at the mitotic spindle of granulosa cells, surrounding the oocyte. Deletion of the RHAMM C-terminus in vivo abolishes its spindle association, resulting in impaired spindle orientation in the dividing granulosa cells, folliculogenesis defects and subsequent female hypofertility. These data reveal the first identified physiological function for RHAMM, during oogenesis, and the importance of this spindle-associated function for female fertility.
机译：产后哺乳动物的卵巢中含有初级卵泡，每个卵泡都包含一个未成熟的卵母细胞，卵母细胞被一层体细胞颗粒细胞所包围。卵母细胞通过卵泡形成达到减数分裂和发育能力。在此过程中，颗粒细胞在卵母细胞周围大量增殖，形成广泛的细胞外基质（ECM），并分化为卵丘细胞。由于ECM成分透明质酸（HA）被认为形成了卵母细胞-颗粒细胞复合物的骨架，因此我们在小鼠中删除了HA介导的运动（RHAMM）基因受体的相关域。尽管不影响HA诱导的信号传导，但这导致卵泡生成缺陷和女性不育。我们报告说野生型RHAMM定位在卵母细胞周围的颗粒细胞的有丝分裂纺锤体。体内RHAMM C末端的删除取消了其纺锤体关联，导致分裂的颗粒细胞中纺锤体定向受损，卵泡形成缺陷和随后的女性不育症。这些数据揭示了卵生过程中RHAMM的第一个生理功能，以及该纺锤体相关功能对女性生育力的重要性。

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