Slit1 可抑制小鼠卵泡发育和雌性生育能力。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Florine Grudet, Emmanuelle Martinot, Philippe Godin, Michael Bérubé, Alain Chédotal, Derek Boerboom
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引用次数: 0

摘要

以前的体外研究表明,SLIT 配体可在调节卵巢颗粒细胞增殖和基因表达以及黄体溶解方面发挥作用。然而,迄今为止还没有对 Slit 基因功能进行过体内研究。在此,我们利用Slit1基因缺失小鼠模型研究了Slit1在卵巢生物学中的潜在作用。研究发现,由于排卵率增加,雌性Slit1-null小鼠的产仔数比野生型小鼠多。Slit1-null动物卵巢重量的增加是由于存在更多的健康窦前卵泡,而闭锁卵泡的数量相近,这表明卵泡募集率增加,闭锁率降低。与此相一致的是,用外源性 SLIT1 处理培养的颗粒细胞,在有或没有 FSH 的情况下都会诱导细胞凋亡,但对细胞增殖没有影响。虽然在Slit1缺失小鼠的颗粒细胞中,FSH反应基因的mRNA水平几乎没有变化,但LH靶基因的mRNA水平却大大增加。最后,在从Slit1-null小鼠体内分离出的颗粒细胞中发现磷酸化AKT水平升高,对培养的颗粒细胞进行SLIT1预处理可抑制FSH和LH增加AKT磷酸化的能力,这表明SLIT1可拮抗促性腺激素信号转导的机制。因此,这些发现首次证明了SLIT配体在卵巢中的生理作用,并将Slit1定义为卵泡发育的新型自分泌/旁分泌调节因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Slit1 inhibits ovarian follicle development and female fertility in mice†.

Previous in vitro studies have suggested that SLIT ligands could play roles in regulating ovarian granulosa cell proliferation and gene expression, as well as luteolysis. However, no in vivo study of Slit gene function has been conducted to date. Here, we investigated the potential role of Slit1 in ovarian biology using a Slit1-null mouse model. Female Slit1-null mice were found to produce larger litters than their wild-type counterparts due to increased ovulation rates. Increased ovarian weights in Slit1-null animals were found to be due to the presence of greater numbers of healthy antral follicles with similar numbers of atretic ones, suggesting both an increased rate of follicle recruitment and a decreased rate of atresia. Consistent with this, treatment of cultured granulosa cells with exogenous SLIT1 induced apoptosis in presence or absence of follicle-stimulating hormone, but had no effect on cell proliferation. Although few alterations in the messenger RNA levels of follicle-stimulating hormone-responsive genes were noted in granulosa cells of Slit1-null mice, luteinizing hormone target gene mRNA levels were greatly increased. Finally, increased phospho-AKT levels were found in granulosa cells isolated from Slit1-null mice, and SLIT1 pretreatment of cultured granulosa cells inhibited the ability of both follicle-stimulating hormone and luteinizing hormone to increase AKT phosphorylation, suggesting a mechanism whereby SLIT1 could antagonize gonadotropin signaling. These findings therefore represent the first evidence for a physiological role of a SLIT ligand in the ovary, and define Slit1 as a novel autocrine/paracrine regulator of follicle development.

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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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