Stromal Senp1 promotes mouse early folliculogenesis by regulating BMP4 expression.

Stromal Senp1 promotes mouse early folliculogenesis by regulating BMP4 expression.
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基质Senp1通过调节BMP4表达促进小鼠早期卵泡发生

DOI:
10.1186/s13578-017-0163-5
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发表时间:
2017
期刊:
影响因子:
7.5
通讯作者:
Min W
Min W
中科院分区:
生物学2区
文献类型:
--
作者:
Tan S;Feng B;Yin M;Zhou HJ;Lou G;Ji W;Li Y;Min W

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哺乳动物卵泡发生,即卵泡的成熟,需要来自卵母细胞和周围细胞(包括基质细胞)的生长因子。然而,基质细胞及其衍生因子调控卵母细胞发育的机制尚不清楚。我们观察到SENP 1是一种小泛素相关修饰物(SUMO)特异性异肽酶,在小鼠卵巢sm 22 α阳性基质细胞中表达。sm 22 α阳性基质细胞与卵泡成熟密切相关。通过使用sm 22 α特异性Cre系统,我们发现SENP 1基质细胞特异性缺失的小鼠表现出减弱的基质-卵泡结合,卵母细胞生长延迟和卵泡成熟,在卵母细胞发育早期卵泡数量和大小减少,导致排卵后期卵巢早衰。机制研究表明,基质SENP 1缺陷诱导基质细胞中BMP 4的下调,伴随着卵母细胞上BMP 4受体BMPR 1b和BMPR 2表达的降低。我们的数据支持蛋白SUMO化调节酶SENP 1通过调节基质和基质-卵母细胞通讯中BMP 4的基因表达在早期卵泡发育中起关键作用。本文的在线版本(doi:10.1186/s13578-017-0163-5)包含补充材料,可供授权用户使用。
Mammalian folliculogenesis, maturation of the ovarian follicles, require both growth factors derived from oocyte and surrounding cells, including stromal cells. However, the mechanism by which stromal cells and derived factors regulate oocyte development remains unclear. We observed that SENP1, a small ubiquitin-related modifier (SUMO)-specific isopeptidase, was expressed in sm22α-positive stromal cells of mouse ovary. The sm22α-positive stromal cells tightly associated with follicle maturation. By using the sm22α-specific Cre system, we show that mice with a stromal cell-specific deletion of SENP1 exhibit attenuated stroma-follicle association, delayed oocyte growth and follicle maturation with reduced follicle number and size at early oocyte development, leading to premature ovarian failure at late stages of ovulating life. Mechanistic studies suggest that stromal SENP1 deficiency induces down-regulation of BMP4 in stromal cells concomitant with decreased expression of BMP4 receptor BMPR1b and BMPR2 on oocytes. Our data support that protein SUMOylation-regulating enzyme SENP1 plays a critical role in early ovarian follicle development by regulating gene expression of BMP4 in stroma and stroma-oocyte communication. The online version of this article (doi:10.1186/s13578-017-0163-5) contains supplementary material, which is available to authorized users.
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