Oocyte maturation is inhibited by adenosine in the presence of follicle- stimulating hormone

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Abstract
Considerable evidence implicates cyclic 3'', 5'' adnenosine monophosphate (AMP) in the maintenance of meiotic arrest of mammalian ooocytes. Since this laboratory previously found that adenosine augmented follicle-stimulating hormone (FSH)-stimulted accumulation of cyclic AMP in oocyte-cumulus-complexes (OCC), in the present studies we investigated the possibility that adenosine inhibits maturation of oocytes. In rat OCC cultured in the presence of FSH, adenosine markedly inhibited oocyte maturation in a dose-dependent and biphasic manner. Maximum inhibition of oocyte maturation was seen with 1-30 .mu.M adenosine in the presence of FSH, and half-maximal inhibition occurred with less than 0.3 .mu.M adenosine. High levels of adenosine (100 .mu.M) did not inhbiit oocyte maturation in the presence of FSH. In the absence of FSH, adenosine showed little effect on oocyte maturation in the present studies, but increased the maximum inhibition of oocyte maturation produced by FSH approximately twofold. Like adenosine, adenosine triphosphate (ATP), adenosine diposphate (ADP), and adenosine 5''-monophosphate (AMP) also inhibited oocyte maturation; whereas adenine, guanosine, inosine, and hypoxanthine were inactive at equivalent levels. The metabolism-resistant adenosine analog (2-chloroadenosine) was as active an inhibitor as adenosine. Inhibition produced by the adenine nucleotides may have been direct or due to conversion to adenosine by extracellular nucleotidases. The concentration dependence and purine specificity for inhibition of oocyte maturation are characteristic of an adenosine receptor-mediated process, but direct evidence for such a mechanism was not shown. The effective concentration of adenosine for inhibition of oocyte maturation is within the range of reported levels of adenosine in biological tissues and fluids. Since this laboratory previously showed that adenosine may be released from granulosa cells in response to FSH, it is possible that adenosine plays a functional, paracrine role in maintenance of meiotic arrest.