Vasorin: a newly identified regulator of ovarian folliculogenesis

Abstract

Members of the TGF-β superfamily take part in the control of folliculogenesis. Vasorin (Vasn) is a newly identified negative regulator of TGF-β signaling whose possible involvement in ovarian physiology has never been studied. Here, we demonstrate that Vasn is expressed in the ovary by somatic cells of follicles, and that its expression is up-regulated by LH. We established a conditional knockout (cKO) mouse model in which Vasn is deleted specifically in granulosa cells of growing follicles from the secondary stage onwards. Using this model, we show that, upon hormonal stimulation, follicle ovulation size is almost 2-fold higher. This enhanced ovulatory response is associated with overactivation of the TGF-β signaling pathway and a lower number of atretic antral follicles. Of importance, we demonstrate that the number of primordial follicles is reduced in prepubertal cKO mouse ovaries, which suggests that the production of VASN by growing follicles protects the ovarian reserve. Finally, analysis of systemic KO mice revealed that the ovarian reserve is almost 2.5-fold higher, which implies that Vasn may also play a role in primordial follicle formation. Overall, our findings reveal that Vasn is a new regulator that exerts an effect on several key ovarian functions, including folliculogenesis, maintenance of the ovarian reserve, and ovulation.-Rimon-Dahari, N., Heinemann-Yerushalmi, L., Hadas, R., Kalich-Philosoph, L., Ketter, D., Nevo, N., Galiani, D., Dekel, N. Vasorin: a newly identified regulator of ovarian folliculogenesis.

From Vascular Smooth Muscle Cells to Folliculogenesis: What About Vasorin?

“…These approaches revealed a widespread expression of Vasn from early developmental stage narrowing as development progresses. In situ hybridization on adult mice confirmed Vasn expression in the coronary artery, aorta, kidney (2), and in ovarian follicles (21). Northern blot analysis on adult mice tissues further confirmed Vasn expression in heart, kidney, lung, liver, and testis (19).…”

“…Along the idea of TGF-β pathway central role, Rimon-Dahari et al explored the role of Vasn in folliculogenesis (21). They first reported vasorin expression in ovaries at all the follicular stages and used Vasn systemic KO mice to analyse mice fertility and folliculogenesis.…”

Childhood experiences of parenting and age at menarche, age at menopause and duration of reproductive lifespan: Evidence from the English Longitudinal Study of Ageing

“…Of importance in explaining our findings might also be stress-related pathways implicated in the decrease of the ovarian reserve before puberty, when the HPG axis is inactive. Such pathways may involve growth factors such as members of the transforming growth factor-β (TGF-β) superfamily [38], whose overactivation due to suppression of their regulators resulted in a considerable decrease of the ovarian reserve in prepubertal mice [39]. Also very important for premature menopause and regulated by growth factors, such as the insulin-like growth factor 1 (IGF1), is the intracellular phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway, which is the master regulator of follicular activation and proliferation [40].…”

Newly Identified Regulators of Ovarian Folliculogenesis and Ovulation

“…Vasorin (Vasn) is a newly identified negative regulator of TGFβ signaling [ 119 ], whose possible involvement in ovarian physiology has recently been studied [ 120 ]. This study demonstrated that Vasn was expressed by the GCs, and that its expression was upregulated by LH.…”