Granulosa cell endothelin-2 expression is fundamental for ovulatory follicle rupture

Abstract

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.

Expression and Contribution of NLRP3 Inflammasome During the Follicular Development Induced by PMSG

“…Interestingly, the present results showed that expressions and activation of NLRP3 inflammasomes in the outside of intrafollicular fluid after PMSG-52 h treatment, suggesting the regional responses in the ovulatory follicles (Duffy et al, 2019), which contributed to the apical stretching and thinning (Duffy et al, 2019). Previous studies have indicated ETs facilitated follicular rupture at the apex (Ko et al, 2006; Choi et al, 2011; Cacioppo et al, 2017) and HIF-1α regulated ovulation-related gene expression (Zhang Z. et al, 2011; Wang et al, 2012; Wang et al, 2015) during the ovulatory process. Therefore, the present study further examined the expressions of HIF-1α and ET-1 and found their expression patterns were similar with NLRP inflammasomes, demonstrating the possible contribution of NLRP inflammasomes to the ovulation.…”

Autozygosity mapping and time-to-spontaneous delivery in Norwegian parent-offspring trios

“…Some of the 14 SIGLEC genes that exist are also expressed in villous and extravillous cytotrophoblasts, decidual cells, as early as eight gestational weeks, and in maternal uterine glands ( 39 , 40 ), suggesting a possible role of SIGLECs in mediating the immune tolerance at the feto-maternal interface. The EDN2 gene (1p34.2 locus) is associated with almost 5% lower time-to-spontaneous onset of delivery ( P -value= 2.3 × 10 −6 ), EDN2 encodes endothelin 2, a strong vasoconstrictor involved in follicular rupture and ovulation; it causes the contraction of the smooth muscle layer surrounding each follicle ( 41 , 42 ).…”

Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7

“…LOX encodes a member of the lysyl oxidase family proteins, which has previously been proposed to promote epithelial to mesenchymal transition in prostate cancer (Gonzalez-Chavarria et al, 2018), and its propeptide domain may display tumor suppressor activities (Agra et al, 2013). EDN2 belongs to the endothelin protein family of secretory vasoconstrictive peptides, and it has already been shown that it is involved in ovulation (Cacioppo et al, 2017). FOLR1 is a member of the folate receptor family, and a previous study showed it is associated with the progression of cervical cancer through the ERK signaling pathway (Liu et al, 2017).…”