Endocrine and molecular milieus of ovarian follicles are diversely affected by human chorionic gonadotropin and gonadotropin-releasing hormone in prepubertal and mature gilts

Abstract

Different strategies are used to meet optimal reproductive performance or manage reproductive health. Although exogenous human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonists (A) are commonly used to trigger ovulation in estrous cycle synchronization, little is known about their effect on the ovarian follicle. Here, we explored whether hCG- and GnRH-A-induced native luteinizing hormone (LH) can affect the endocrine and molecular milieus of ovarian preovulatory follicles in pigs at different stages of sexual development. We collected ovaries 30 h after hCG/GnRH-A administration from altrenogest and pregnant mare serum gonadotropin (eCG)-primed prepubertal and sexually mature gilts. Several endocrine and molecular alternations were indicated, including broad hormonal trigger-induced changes in follicular fluid steroid hormones and prostaglandin levels. However, sexual maturity affected only estradiol levels. Trigger- and/or maturity-dependent changes in the abundance of hormone receptors (FSHR and LHCGR) and proteins associated with lipid metabolism and steroidogenesis (e.g., STAR, HSD3B1, and CYP11A1), prostaglandin synthesis (PTGS2 and PTGFS), extracellular matrix remodeling (MMP1 and TIMP1), protein folding (HSPs), molecular transport (TF), and cell function and survival (e.g., VIM) were observed. These data revealed different endocrine properties of exogenous and endogenous gonadotropins, with a potent progestational/androgenic role of hCG and estrogenic/pro-developmental function of LH.

Attainment of Sexual Maturity and Gonadotropin Priming in Gilts Determine Follicular Development, Endocrine Milieu and Response to Ovulatory Triggers

“…It is thought that CYP17A1, the last enzyme in the biosynthesis of androgens, becomes the rate-limiting enzyme of follicular estrogen synthesis in pigs [ 22 ]. Furthermore, our recent results and previous studies [ 13 , 14 ] confirmed the hypothesis that the availability of substrate, but not the magnitude of CYP19A1 mRNA/protein expression, is critical for maintaining E2 synthesis in the porcine preovulatory follicle.…”

“…In conclusion, this study, together with our two already published studies [ 13 , 14 ], indicates that sexual maturity, altrenogest and exogenous gonadotropins significantly affect endocrine and molecular regulators of ovarian follicle development and function in gilts. Whereas the diversity of hCG and LH (released by delivered GnRH) action was presented in detail by Ziecik and co-workers (2021), this study compared eCG- and hFSH-priming effects in gilts.…”

“…This could reflect the different pattern of LHCGR expression in granulosa cells and theca layer during the follicle maturation [ 1 ]. Our recent results showed that the administration of ovulation stimuli in vivo, i.e., hCG and GnRH-A (to induce a native LH release), affected steroidogenesis in preovulatory follicles, and that the attainment of sexual maturity was strongly visible in altrenogest- and eCG-primed gilts [ 14 ]. In this study, hCG preferentially affected production of P4, A4 and T, however, native LH and sexual maturity act as an advantage for E2 concentration in the follicular fluid.…”

“…RNA isolation and gene abundance analyses were performed as previously described [ 14 ]. Briefly, total RNA was isolated from the walls of preovulatory follicles using a mirVana microRNA Isolation Kit (Invitrogen, Thermo Fisher Scientific, Waltham, MA, USA) and genomic DNA was removed by DNAse I (Invitrogen) according to the manufacturer’s instructions.…”

“…To explain the possible mechanism of the combined action of altrenogest and exogenous gonadotropins in follicular development and their potential transformation into cysts, we focused our recent studies on the effect of altrenogest [ 13 ] and exogenous gonadotropin (hCG vs. GnRH-A-induced LH) [ 14 ] administration on ovarian folliculogenesis, endocrine and molecular milieus of the preovulatory follicles in prepubertal and sexually mature gilts. We showed that altrenogest equivocally affects folliculogenesis and the development of growing follicles.…”