TGFβ1 Role in Fine Balancing Ovulation

The ovary homes the oocytes reservoir, the development of each is regulated by somatic granulosa and theca cells, comprising the follicle. Advanced stages of folliculogenesis, culminating in ovulation, which is controlled by the pituitary FSH&LH and involve members of the TGFβ family members, however, the precise role of TGFβ1 in ovulation remains unclear. We hypothesize that TGFβ1 regulates the FSH receptors (FSHR), which in turn stimulate the LHR expression, thus controlling the ovarian response to the pituitary gonadotropins. To elucidate TGFβ1 role we utilized two transgenic mouse models. In one such model Vasorin (Vasn), an extracellular inhibitor of TGFβ, is deleted exclusively in granulosa cells (GCs) of growing follicles, resulting in higher availability of TGFβ1 (Vasn cKO). In the second model, the "TGFβ1 switch" was turned off by specific deletion of TGFβR2 in GCs of growing follicles. We show that in Vasn cKO mice, the number of FSHR and LHR expressing follicles is higher, resulting in a larger number of expanded cumulus-oocyte complexes and a two-fold increase in ovulation size. In the TGFβR2 cKO, the number of FSHR and LHR presenting follicles was reduced but the ovulation size remains unchanged, possibly suggesting a compensating mechanism. Our results so far, place TGFβ1 as a positive upstream regulator of FSHR expression, thus augmenting the ovulatory response. High throughput RNA sequencing of sorted GCs from the different transgenic mouse models is presently performed to decipher the mechanism of action by which TGFβ1 affects the expression of FSHR.