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首页> 外文期刊>Journal of Cellular Physiology >Inhibition of mTOR Signaling Pathway Delays Follicle Formation in Mice
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Inhibition of mTOR Signaling Pathway Delays Follicle Formation in Mice

机译:抑制mTOR信号通路延迟小鼠卵泡形成

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In mammalian ovaries, follicle assembly requires proper germ cell cyst breakdown and the invasion of somatic cells to encapsulate individual oocytes. Abnormalities in this process lead to a number of pathologies such as premature ovarian failure and infertility. As a conserved pathway regulating cell growth and metabolism in response to growth factors and nutrients, the roles of mTOR signaling in follicular development have been extensively studied in recent years. However, its functions during follicle formation remain unknown. In this study, the expression of p-rpS6 (phospho-ribosomal proteinS6), a downstream marker of mTORC1, showed dynamic changes in perinatal ovaries. When E18.5 ovaries, which mainly contained germ cell nests, were incubated with the mTOR inhibitors Rapamycin and Torin1 for 24h, follicle assembly was delayed with differential somatic cell invasion into germ cell cyst among the groups. After transplanting treated or untreated ovaries into kidney capsules of recipient ovariectomized mice, follicular development was blocked in treated ovaries, as shown by fewer antral follicles and a higher proportion of primordial follicles. Further studies showed a significant decrease in somatic cell proliferation and the expression of marker genes related to follicular development (Kitl, Kit, Gdf9, Bmp15, Zp3, and Amhr2) in treated ovaries. Moreover, the addition of KITL, a growth factor that is mainly produced by pregranulosa cells during germ cell nest breakdown, rescued the extension of follicle formation induced by mTOR inhibitors. These results suggest that KITL functions downstream of mTOR in somatic cells to regulate their communication with oocytes during follicle formation. J. Cell. Physiol. 232: 585-595, 2017. (c) 2016 Wiley Periodicals, Inc.
机译:在哺乳动物卵巢卵泡组装要求适当的生殖细胞囊肿破裂和入侵体细胞的封装卵母细胞。数量的病态如卵巢功能失败和不孕。调节细胞生长和代谢的反应生长因子和营养的作用在卵泡发展mTOR信号近年来被广泛研究。然而,它的功能在卵泡的形成仍然未知。p-rpS6 (phospho-ribosomal proteinS6)下游mTORC1的标志,显示动态围产期卵巢的变化。主要包括生殖细胞巢,是吗mTOR雷帕霉素和孵化Torin1 24 h,卵泡大会被推迟与微分体细胞入侵的细菌在组织细胞囊肿。或未经治疗卵巢肾胶囊治疗收件人切除卵巢的老鼠,滤泡在治疗卵巢,发展受阻显示更少的窦的毛囊和更高比例的原始卵泡。研究显示在躯体明显降低细胞增殖和标记的表达卵泡发育相关基因(Kitl装备、Gdf9 Bmp15, Zp3 Amhr2)治疗卵巢。因素主要由pregranulosa细胞在生殖细胞巢,获救扩展引起的毛囊形成的mTOR。下游mTOR的体细胞功能与卵母细胞在调节他们的沟通滤泡形成。585 - 595年,2017年。

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