ADAM10-Notch signaling governs the recruitment of ovarian pregranulosa cells and controls folliculogenesis in mice
ADAM10-Notch signaling governs the recruitment of ovarian pregranulosa cells and controls folliculogenesis in mice
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ADAM10-Notch 信号传导控制小鼠卵巢前颗粒细胞的募集并控制卵泡发生
DOI：
10.1242/jcs.184267
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发表时间：
2016-06-01
影响因子：
4
通讯作者：
Xia, Guoliang
中科院分区：
文献类型：
--
作者：
Feng, Lizhao;Wang, Yijing;Xia, Guoliang
卵泡是哺乳动物卵巢中雌性生殖的基本功能单位。我们在这里表明，蛋白a去整合素和金属蛋白酶结构域10（ADAM 10），细胞表面脱落酶，在控制原始卵泡形成中起着不可或缺的作用，通过调节小鼠卵泡支持细胞的募集。我们证明，在体外抑制ADAM 10或在体内删除ADAM 10破坏生殖细胞囊肿破裂和原始卵泡的形成。使用细胞谱系追踪的方法，我们表明，ADAM 10通过调节LGR 5阳性卵泡支持祖细胞的分化和增殖来管理卵泡细胞的募集。通过检测FOXL 2阳性前颗粒细胞的发育，我们发现抑制ADAM 10可以减少围产期卵巢中FOXL 2阳性细胞的数量。此外，抑制ADAM 10抑制Notch信号传导的激活，阻断Notch信号传导也破坏了卵泡祖细胞的募集。综上所述，这些结果表明，在卵巢体细胞中的ADAM 10-Notch信号转导通过控制卵巢前颗粒细胞的发育来调控原始卵泡的形成。卵泡支持细胞的适当募集对小鼠卵巢储备的建立至关重要。
Ovarian follicles are the basic functional units of female reproduction in the mammalian ovary. We show here that the protein a disintegrin and metalloproteinase domain 10 (ADAM10), a cell surface sheddase, plays an indispensable role in controlling primordial follicle formation by regulating the recruitment of follicle supporting cells in mice. We demonstrate that suppressing ADAM10 in vitro or deletion of Adam10 in vivo disrupts germline cyst breakdown and primordial follicle formation. Using a cell lineage tracing approach, we show that ADAM10 governs the recruitment of ovarian follicle cells by regulating the differentiation and proliferation of LGR5-positive follicle supporting progenitor cells. By detecting the development of FOXL2-positive pregranulosa cells, we found that inhibiting ADAM10 reduced the number of FOXL2-positive cells in perinatal ovaries. Furthermore, inhibiting ADAM10 suppressed the activation of Notch signaling, and blocking Notch signaling also disrupted the recruitment of follicle progenitor cells. Taken together, these results show that ADAM10-Notch signaling in ovarian somatic cells governs the primordial follicle formation by controlling the development of ovarian pregranulosa cells. The proper recruitment of ovarian follicle supporting cells is essential for establishment of the ovarian reserve in mice.