Adenosine blocks hormone-induced meiotic maturation by suppressing purine de novo synthesis

We have examined adenosine (Ado) suppression of FSH-induced germinal vesicl e breakdown (GVB) and its relationship to purine de novo synthesis. Oocyte- cumulus cell complexes (OCC) from PMSG-primed, immature mice were cultured 17-18 hr in medium containing 4 mM hypoxanthine (HX) or 300 mu M dibutyryl cAMP (dbcAMP) to maintain meiotic arrest, and FSH was added to stimulate me iotic maturation. In the absence of FSH, Ado (1-250 mu M) had no effect in dbcAMP-arrested oocytes but dose-dependently suppressed maturation in HX-tr eated oocytes. FSH-induced maturation was prevented by Ado, though more eff ectively in dbcAMP-supplemented cultures. Ado affected the magnitude, but n ot the kinetics pattern, of the response to FSH. Inosine also blocked meiot ic induction, but only in dbcAMP-arrested oocytes. Purine de novo synthesis was nearly doubled in OCC by FSH treatment, and this response was complete ly prevented by Ado. FSH had no effect on HX salvage, although Ado reduced this activity by 98%. Inosine effects on metabolism were intermediate betwe en the control and Ado groups. Experiments with radiolabeled energy substra tes showed that Ado suppressed FSH activation of the pentose phosphate path way but did not prevent significant activation of glycolysis or oxidation o f pyruvate. Finally, in cultured follicles from primed mice, hCG-induced ma turation was blocked by Ado as effectively as by the purine de novo synthes is inhibitor, azaserine. It is concluded that Ado has an inhibitory action on hormone-induced maturation that is due, at least in part, to suppression of glucose metabolism, leading to compromised purine de novo synthesis. Mo l. Reprod. Dev. 56:172-179, 2000. (C) 2000 Wiley-Liss, Inc.