Hypoxanthine is involved in promoting the activation of mouse primordial follicles

In each wave, only a small portion of primordial follicles are selectively activated into the growing follicular pool, and the majority of primordial follicles remain in a relatively quiescent state. Hypoxanthine is present in the follicular fluid with high concentrations and inhibits phosphodiesterase activity. In this study, hypoxanthine synthase purine nucleoside phosphorylase (Pnp) was expressed in oocytes, and its expression levels increased progressively with oocyte growth, accompanied by an increase in ovarian hypoxanthine levels. Ovarian hypoxanthine levels were significantly increased in equine chorionic gonadotropin-primed mice, accompanied by an increase in primary follicle numbers. Hypoxanthine significantly increased the number of growing follicles and the levels of cyclic adenosine monophosphate (cAMP) and phosphorylated protein kinase B (p-Akt) in cultured ovaries. Hypoxanthine with intraperitoneal injection in neonatal mice also significantly increased growing follicle numbers and p-Akt protein levels in the ovaries. Additionally, oral BCX-1777 in adolescent mice, a PNP inhibitor, significantly decreased hypoxanthine levels and growing follicle numbers in the ovaries. Thus, hypoxanthine promotes mouse primordial follicle activation through cAMP-PI3K/Akt pathway. The high levels of hypoxanthine produced by the preovulatory fully-grown oocytes may contribute to the promotion of the cyclic activation of primordial follicles.