In vivo and in vitro effects of GnRH antagonist treatment on steroidogenesis and folliculogenesis in the ovary of cyclic mice.

CONTEXT: Gonadotropin-releasing hormone antagonists (GnRH-Anta) can modulate reproductive hormonal activity without inducing the initial surge in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) typically associated with GnRH agonists. Despite growing interest, the effects of GnRH antagonists on ovarian function, particularly under varying physiological conditions, remain inadequately understood.

AIMS: This study aimed to evaluate the effects of different doses of GnRH-Anta on morphological and physiological changes in the ovaries of cyclic mice, both in vivo and in vitro.

METHODS

Cyclic female mice were administered various doses of GnRH-Anta for eight consecutive days. To assess direct effects, ovaries collected from proestrus-stage mice were cultured with different concentrations of GnRH-Anta for 24 h at 37°C.

KEY

RESULTS

The administration of GnRH-Anta for eight consecutive days exhibited dose-dependent inhibitory effects on follicular development and luteinization, with a reduced number of growing follicles. This was accompanied by reduced circulating concentrations of progesterone and estradiol, subnormal luteal morphology, and a dose-dependent decline in the ovarian expression of 3β-hydroxysteroid dehydrogenase (3β-HSD), steroid receptors. An increase in atretic follicles observed was closely associated with elevated expression of apoptotic markers. The in vitro study showed inhibitory effect on the ovary even in the presence of LH.

CONCLUSIONS

GnRH-Anta treatment affects various aspects of ovarian physiology, including follicular development, apoptosis, and steroidogenesis, in a dose- and context-dependent manner, influenced by the mode of treatment and the presence or absence of LH.

IMPLICATIONS: GnRH-Anta may be used to suppress the release of LH and FSH, preventing premature ovulation and helping manage various reproductive conditions.