Multiple cAMP phosphodiesterases act together to prevent premature oocyte meiosis and ovulation

Giulia Vigone, Leia C. Shuhaibar, Jeremy R. Egbert, Tracy F. Uliasz, Matthew A. Movsesian, Laurinda A. Jaffe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Luteinizing hormone (LH) acts on the granulosa cells that surround the oocyte in mammalian preovulatory follicles to cause meiotic resumption and ovulation. Both of these responses are mediated primarily by an increase in cyclic adenosine monophosphate (cAMP) in the granulosa cells, and the activity of cAMP phosphodiesterases (PDEs), including PDE4, contributes to preventing premature responses.However, two other cAMP-specific PDEs, PDE7 and PDE8, are also expressed at high levels in the granulosa cells, raising the question of whether these PDEs also contribute to preventing uncontrolled activation of meiotic resumption and ovulation. With the use of selective inhibitors, we show that inhibition of PDE7 or PDE8 alone has no effect on the cAMP content of follicles, and inhibition of PDE4 alone has only a small and variable effect. In contrast, a mixture of the three inhibitors elevates cAMP to a level comparable with that seen with LH. Correspondingly, inhibition of PDE7 or PDE8 alone has no effect on meiotic resumption or ovulation, and inhibition of PDE4 alone has only a partial and slow effect. However, the fraction of oocytes resumingmeiosis and undergoing ovulation is increased when PDE4, PDE7, and PDE8 are simultaneously inhibited. PDE4, PDE7, and PDE8 also function together to suppress the premature synthesis of progesterone and progesterone receptors,which are required for ovulation.Our results indicate that three cAMPPDEs act in concert to suppress premature responses in preovulatory follicles.

Original languageEnglish (US)
Pages (from-to)2142-2152
Number of pages11
JournalEndocrinology
Volume159
Issue number5
DOIs
StatePublished - May 1 2018

ASJC Scopus subject areas

  • Endocrinology

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