Effects of Growth and Differentiation Factor 9 and Bone Morphogenetic Protein 15 overexpression on the steroidogenic metabolism in bovine granulosa cells in vitro

Abstract

Granulosa cells (GCs) play important roles in the regulation of ovarian functions, and in vitro culture is a relevant model for the study of steroidogenesis in ovarian follicles.Thus, growth factors secreted by the oocyte, like Growth and Differentiation Factor 9 (GDF9) and Bone Morphogenetic Protein 15 (BMP15), play an important part in the luteinization of granulosa cells. The aim of this work was to express GDF9 and BMP15 genes in bovine GCs in vitro and evaluate their effects on the luteinization process. Samples of culture medium and GCs transfected with GDF9 and BMP15 were obtained for 21 consecutive days to analyse the steroidogenic hormones' concentration (progesterone (P 4 ) and estradiol (E 2 )) and the expression of STAR, GDF9 and BMP15 and their respective receptors. The results demonstrated an inhibitory effect of GDF9 and BMPF15 on P 4 secretion in bovine GCs cultured in vitro.Moreover, our study demonstrated the entire expression of their respective receptors (TGFBR1, BMPR1B and BMPR2) and the inhibition of the steroidogenic marker, STAR gene. This work sheds light on a novel biological function of BMP15 and GDF9 in bovine GCs physiology, which could elucidate a non-described biological role for GDF9 and BMP15 in bovine granulosa cells' metabolism.

Local regulation of antral follicle development and ovulation in monovulatory species

“…In in vitro culture, BMP15 and GDF9 have also been shown to act synergistically to induce complexes of bovine granulosa cells to form antrum-like structures ( Alam et al, 2018 ). However, in bovine granulosa cells cultured in vitro in a homologous system, increased expression of GDF9 and BMP15 caused cellular luteinization ( Paulini and Melo, 2021 ), which resembles what we have observed when the intrafollicular concentration of BMP15 was increased in dominant and preovulatory follicles in vivo .…”

Vitamin D Effects on Folliculogenesis via Ovarian Paracrine Factors

“…GDF9 also reducing luteinization via progesterone reduction [17]. GDF9 and BMP15 has an inhibitory effect on progesterone secretion in granulosa cells [21]. In a recent study, it was reported that BMP15 increased progesterone production by cumulus cells [22].…”