Phosphodiesterase 3 inhibitors selectively block the spontaneous resumption of meiosis by macaque oocytes in vitro

J. T. Jensen, K. M. Schwinof, M. B. Zelinski-Wooten, M. Conti, L. V. DePaolo, R. L. Stouffer

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Background: The purpose of this study was to determine whether phosphodiesterase (PDE) 3 inhibitors selectively prevent the resumption of meiosis in primates. Methods: Immature oocytes (intact germinal vesicles) obtained from large pre-ovulatory follicles following ovarian stimulation in rhesus macaques were incubated with or without various doses of the PDE3 inhibitors, cilostamide, milrinone or ORG 9935, or a selective PDE4 inhibitor, rolipram. Oocytes were observed for germinal vesicle breakdown (GVBD) as an indicator of resumption of meiosis. Results: At 24 h, 72 of 121 (60%) control oocytes progressed to GVBD compared with 9/34 (27%, P < 0.01), 4/36 (11.1%, P < 0.01) and 0/28 (0%, P < 0.01) oocytes incubated with ORG 9935 at 0.1, 0.5 and 1.0 μmol/l respectively. Similar results were achieved at 24 h with 1.0 μmol/l cilostamide (2/24 oocytes, 8%, P < 0.01) and 100 μmol/l milrinone (2/32, 6%, P < 0.01). In contrast, no significant difference in GVBD was noted between control oocytes and those incubated with up to 100 μmol/l rolipram for 24 h (43/58, 74%) or 48 h (44/58, 76%). Conclusions: These experiments establish the specificity and dose-dependent ability of PDE3, but not PDE4, inhibitors to block resumption of meiosis in macaque oocytes in vitro. Thus, PDE3 inhibitors have potential use as contraceptives in primates.

Original languageEnglish (US)
Pages (from-to)2079-2084
Number of pages6
JournalHuman Reproduction
Volume17
Issue number8
DOIs
StatePublished - 2002

Keywords

  • Contraception
  • Meiosis
  • Non-human primate
  • Oocyte
  • Phosphodiesterase 3 inhibitor

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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