Induction of M-phase entry of prophase-blocked mouse oocytes through microinjection of okadaic acid, a specific phosphatase inhibitor.
We report that a specific inhibitor of types 1 and 2A phosphatases, okadaic acid (OA), induces germinal vesicle break down (GVBD) and chromosome condensation when microinjected into denuded mouse oocytes maintained in prophase block by analogs of cAMP, inhibitors of phosphodiesterase, or a tumor-promoting phorbol ester. GVBD and chromosome condensation are also observed when incompetent oocytes are similarly injected with OA, this effect being dependent on the oocyte diameter. Marked changes in cell shape, cytoskeletal organization, and chromosome condensation with abnormal or abortive spindle formation are associated with such injections. The polar body is not formed. These results led to the conclusions that in mouse oocytes, OA acts distal to both the cAMP-modulated pathway involved in meiotic arrest and the inhibitory action exerted by tumor-promoting phorbol esters.
Department of Obstetrics and Gynaecology, Hôpital Cantonal Universitaire, Geneva, Switzerland.
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Gavin
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Tsukitani
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Schorderet-Slatkine
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002875:Chromosomes / Q000187:drug effects; D004988:Ethers, Cyclic / Q000494:pharmacology*; D066298:In Vitro Techniques; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D008845:Microinjections; D019319:Okadaic Acid; D009865:Oocytes / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011418:Prophase / Q000187:drug effects
D004988:Ethers, Cyclic; D019319:Okadaic Acid; D015240:Phorbol 12,13-Dibutyrate; D003994:Bucladesine; D010749:Phosphoprotein Phosphatases; D015056:1-Methyl-3-isobutylxanthine