Abstract
PURPOSE: Ovulation is a highly regulated inflammatory process that involves the initiation and timely resolution of the inflammation for efficient oocyte maturation. During this process, glucocorticoids accumulate in the pre-ovulatory follicular environment as an anti-inflammatory mediator. However, their temporal regulation, endogenous synthesis, and functional significance on oocyte maturation and subsequent developmental competence remain unclear. METHODS: Corticosterone levels in reproductive tract fluid and serum, alongside the expression and localization of related markers, including glucocorticoid receptors (NR3C1), were analyzed in granulosa cells (GC) and cumulus cells (CC) during gonadotropin stimulation. The functional relevance of corticosterone was evaluated by inhibiting endogenous corticosterone synthesis using metyrapone (MET) and by supplementing exogenously during in vitro maturation (IVM) conditions. RESULTS: Human chorionic gonadotropin (hCG) increased follicular corticosterone at 8 h and upregulated steroidogenic markers (Cyp11a1, Cyp11b1, and Cyp21a1) while downregulating the inactivating enzyme Hsd11b2. MET significantly inhibited FSH-mediated endogenous corticosterone synthesis, resulting in poor IVM outcomes, and supplementation of exogenous corticosterone enhanced the IVM outcome, mitigated the MET effect, and maintained inflammatory balance. CONCLUSIONS: Gonadotropin induces a transient surge of ovarian corticosterone that supports in vivo maturation. Supplementing physiological levels of corticosterone during in vitro maturation (IVM) promotes oocyte maturation probably through cumulus cells.