Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, 61802, USA.
Department of Obstetrics & Gynecology, University of Kentucky, Lexington, KY, 40536, USA.
Sci Rep. 2017 Apr 11;7(1):817. doi: 10.1038/s41598-017-00943-w.
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.
排卵取决于许多因素，这些因素介导卵泡生长、血管生成，最终通过卵泡破裂释放卵母细胞。内皮素-2（EDN2）是一种有效的血管收缩剂，在卵泡破裂前由黄体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，进行了手术移植和新型条件性敲除小鼠实验，并对其进行了分析。条件性敲除小鼠利用一种新的 iCre，由 Esr2 启动子驱动，选择性地去除 Edn2。卵巢中 Edn2 表达缺失显著损害卵泡破裂和生育能力。当 Edn2KO 小鼠的卵巢移植到野生型受体中时，经过激素刺激后，黄体中含有未排卵卵母细胞的数量显著增加（1.0 个比 5.4 个，p=0.010）。在颗粒细胞中选择性地消融 Edn2 后，Esr2-Edn2KO 母鼠排卵的卵母细胞减少（3.8 个比 16.4 个/卵巢），产仔数减少（4.29±1.02 个比 8.50 个/母鼠）。然而，每对的妊娠次数没有差异，生殖轴仍然完整。Esr2-Edn2KO 卵巢的窦卵泡比例较高，黄体较少；卵泡进展到窦状期，但许多卵泡无法破裂。颗粒细胞中内皮素受体 A 的条件性缺失也会减少排卵，但不会影响生育能力。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能力的关键触发因素。
