Role of Phosphodiesterase 3A in Regulation of Diplotene Arrest of Mammalian Oocytes

Anumegha Gupta, Alka Sharma, M

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) are a group of enzymes that regulate cyclic nucleotides such as cyclic adenosine 3’, 5’ monophosphate (cAMP) and cyclic guanosine 3’, 5’ monophosphate (cGMP) level in mammalian oocytes. Among all subtypes of PDEs family, PDE 3A is specifically located in the cytoplasm of oocyte. The cAMP is generated in the granulosa cells as well as in oocyte whereas cGMP is produced only in the granulosa cells of preovulatory follicles. PDE 3A hydrolyzes cAMP with great affinity than cGMP in the oocyte. Decrease of oocyte cAMP level initiates downstream pathway to destabilize maturation promoting factor (MPF) that finally results in meiotic resumption from diplotene arrest. On the other hand, specific PDE inhibitors such as cilostamide, milrinone, ORG 9935 and cilostazol reversibly inhibit enzyme activity and prevent cAMP hydrolysis. High level of intraoocyte cAMP inhibits spontaneous meiotic resumption and maintains diplotene arrest in follicular oocyte. Indeed, PDE inhibitors are choice to prevent spontaneous meiotic resumption both in vivo as well as under in vitro culture conditions to study the meiotic cell cycle regulation in mammalian oocytes.