Human Reproduction, Vol. 17, No. 8, 2079-2084,
August 2002
© 2002 European Society of Human Reproduction and Embryology
Phosphodiesterase 3 inhibitors selectively block the spontaneous resumption of meiosis by macaque oocytes in vitro
1 Department of Obstetrics and Gynecology and Division of Reproductive Sciences, Oregon Regional Primate Research Center, Oregon Health & Science University, Portland, OR 97201, 2 Division of Reproductive Sciences, 3 Department of Physiology and Pharmacology, Oregon Regional Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, 4 Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 and 5 Reproductive Sciences Branch, Center for Population Research, NICHD, NIH, Bethesda, MD, USA
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.
Key words: contraception/meiosis/non-human primate/oocyte/phosphodiesterase 3 inhibitor
6 To whom correspondence should be addressed. E-mail: jensenje{at}ohsu.edu.
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