Genetics of male infertility

In the follicles of the mammalian and amphibian ovary, oocyte maturation is arrested at the prophase of the first meiotic division. Prior to ovulation , oocytes re-enter the cell cycle, complete the meiotic division and extrud e the first polar body. Work from several laboratories including ours has p rovided evidence that the cAMP-mediated signal trannsduction pathways play an important role in the regulation of meiosis, the cyclic nucleotide actin g as a negative regulator of maturation. Since cAMP can be regulated both a t the level of synthesis and degradation, our laboratory is investigating t he role of phosphodiesterases (PDE) in the control of cAMP levels of oocyte s. Using pharmacological and molecular tools, we have determined that a PDE 3 is the enzyme involved in the control of cAMP levels in the oocytes. In v itro and in vivo studies have established that inhibition of the oocyte PDE 3 blocks resumption of meiosis. Furthermore, we have provided evidence that activation of a PDE is per se sufficient to cause resumption of meiosis in an amphibian oocyte model. The pathways regulating this PDE isoform expres sed in the oocyte is under investigation, as they may uncover the physiolog ical signals controlling meiosis. (C) 1998 Elsevier Science Ireland Ltd. Al l rights reserved.