Granulosa cell endothelin-2 expression is fundamental for ovulatory follicle rupture.
Granulosa cell endothelin-2 expression is fundamental for ovulatory follicle rupture.
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DOI：
10.1038/s41598-017-00943-w
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发表时间：
2017-04-11
影响因子：
4.6
通讯作者：
Ko C
中科院分区：
文献类型：
--
作者：
Cacioppo JA;Lin PP;Hannon PR;McDougle DR;Gal A;Ko C
排卵取决于介导卵泡生长、血管形成以及最终通过卵泡破裂释放卵母细胞的多种因素。内皮素-2 (EDN2) 是一种有效的血管收缩剂，在卵泡破裂前由排卵期卵泡的颗粒细胞短暂产生，并诱导卵巢收缩。为了确定 Edn2 表达的作用，对手术移植小鼠和新型条件敲除小鼠进行超排卵并进行分析。条件敲除小鼠利用由 Esr2 启动子驱动的新 iCre 来选择性去除 Edn2。在卵巢 Edn2 表达缺失的情况下，卵泡破裂和生育能力显着受损。当Edn2KO小鼠的卵巢移植到野生型受体中时，在激素刺激后，含有未排卵卵母细胞的黄体明显增多（1.0 vs. 5.4，p = 0.010）。在颗粒细胞中选择性去除 Edn2 后，Esr2-Edn2KO 母鼠的排卵卵母细胞数量减少（每卵巢 3.8 个卵母细胞 vs. 16.4 个卵母细胞），窝产仔数也减少（4.29±1.02 只幼崽/母鼠 8.50 个）。然而，每次配对的怀孕次数没有差异，并且生殖轴保持完整。 Esr2-Edn2KO卵巢具有较高的窦卵泡百分比和较少的黄体；卵泡进展到窦期，但许多卵泡无法破裂。颗粒细胞内皮素受体 A 的条件性丧失也会减少排卵，但不影响生育力。这些数据表明 EDN2 诱导的卵巢内收缩是正常排卵和随后生育的关键触发因素。
Ovulation is dependent upon numerous factors mediating follicular growth, vascularization, and ultimately oocyte release via follicle rupture. Endothelin-2 (EDN2) is a potent vasoconstrictor that is transiently produced prior to follicle rupture by granulosa cells of periovulatory follicles and induces ovarian contraction. To determine the role of Edn2 expression, surgical transplant and novel conditional knockout mice were super-ovulated and analyzed. Conditional knockout mice utilized a new iCre driven by the Esr2 promoter to selectively remove Edn2. Follicle rupture and fertility were significantly impaired in the absence of ovarian Edn2 expression. When ovaries of Edn2KO mice were transplanted in wild type recipients, significantly more corpora lutea containing un-ovulated oocytes were present after hormonal stimulation (1.0 vs. 5.4, p = 0.010). Following selective ablation of Edn2 in granulosa cells, Esr2-Edn2KO dams had reduced oocytes ovulated (3.8 vs. 16.4 oocytes/ovary) and smaller litters (4.29 ± l.02 vs. 8.50 pups/dam). However, the number of pregnancies per pairing was not different and the reproductive axis remained intact. Esr2-Edn2KO ovaries had a higher percentage of antral follicles and fewer corpora lutea; follicles progressed to the antral stage but many were unable to rupture. Conditional loss of endothelin receptor A in granulosa cells also decreased ovulation but did not affect fecundity. These data demonstrate that EDN2-induced intraovarian contraction is a critical trigger of normal ovulation and subsequent fecundity.