β-Catenin/Tcf signaling in murine oocytes identifies nonovulatory follicles

Abstract

WNTS are secreted glycoprotein molecules that signal through one of three signaling pathways. The best-characterized pathway involves stabilization of the multifunctional protein b-catenin, which in concert with members of the T-cell factor (Tcf) family activates specific gene transcription. We have examined putative Wnt/b-catenin in the murine ovary using transgenic mice harboring a reporter construct that activates b-galactosidase (lacZ) expression in response to b-catenin/Tcf binding (TopGal mice). Primordial and primary follicles did not stain for lacZ, and the proportion of b-catenin/Tcf signaling oocytes was lower than that of nonsignaling oocytes throughout estrous cycle. b-Catenin/Tcf signaling oocytes were observed in follicles from the secondary stage of development and their proportion increased with follicular maturation (secondary follicles, 20%; early antral and antral follicles, 70%). In contrast, the majority (O90%) of ovulated oocytes did not stain for lacZ. As the oocyte possesses components for WNT signal transduction, our data suggest that b-catenin/Tcf signaling is involved in the development of follicular ovulatory capability and identifies nonovulatory follicles.

Effects of dietary quercetin on female fertility in mice: implication of transglutaminase 2

“…Previously, we showed that quercetin inhibits the enzyme TG2 and its downstream intracellular signalling including the β-catenin pathway (Beazley et al 2012, 2013 a ), both of which have been implicated in fertility (Fujimoto et al 1996; Tulac et al 2003; Kabir-Salmani et al 2005; Fan et al 2010; Liu et al 2010; Usongo et al 2012; Wetendorf and DeMayo 2012). We therefore reasoned that if quercetin effects involved the inhibition of TG2 then quercetin supplement would not affect fertility in TG2-null female mice.…”

“…Further, loss of TG2 attenuates quercetin effects on female reproduction observed in wild-type mice, in agreement with quercetin acting via inhibition of TG2. A plausible mechanism for the involvement of TG2 relates to its ability to activate the β-catenin signalling pathway (Beazley et al 2013 a ), which in the normal ovary is associated with non-ovulatory follicles (Usongo et al 2012) and can impair ovulation (Fan et al 2010). Therefore, it can be proposed that blocking TG2-mediated β-catenin signalling with quercetin (Beazley et al 2013 a ) may allow for enhanced ovulation; however, further studies will be necessary to directly establish the link between quercetin, TG2 and β-catenin in this process.…”

“…TG2 is present in the endometrial epithelium where it participates in adhesion and migratory events during embryo implantation (Fujimoto et al 1996; Kabir-Salmani et al 2005). In addition, TG2 regulates various signalling cascades, including the canonical β-catenin pathway (Beazley et al 2012) that has been implicated in regulating ovulation (Fan et al 2010; Usongo et al 2012). …”

Soma influences GSC progeny differentiation via the cell adhesion-mediated steroid-let-7-Wingless signaling cascade that regulates chromatin dynamics

“…Slight variations in β-catenin amounts and/or its cellular localization have a profound effect on cell status. While functional studies indicate that Wnt/Wg signaling has a role in several aspects of ovarian function including folliculogenesis and steroidogenesis ( Boyer et al, 2010 ; Usongo et al, 2012 ), a number of questions regarding its functions in the germline remain open.…”

A Role of MicroRNAs in Cell Differentiation During Gonad Development

“…Knockdown of miR-320 in mouse MII oocytes causes a decrease in the number of two-cell embryos and blastocysts, as well as an aberration in the expression of components of the WNT signaling pathway (Feng et al 2015). Though the WNT signaling pathways were studied in oocytes mainly in regard to early embryonic development, the canonical WNT signaling pathway is active in mouse oocytes from the stage of secondary follicle; its activity increases as the follicle grows, concomitantly with an increase in oocyte diameter, but it is undetectable in mature MII oocytes (Usongo et al 2012). Along with the possible role of WNT in modulating the actin cytoskeleton (Akiyama and Kawasaki 2006) and its cross talk with the PI3K/AKT signaling pathway (reviewed by Boyer et al 2010), it is of great interest to explore the involvement of miR-320 in oocyte maturation and emphasize its role as a regulator of WNT signaling.…”