Hum. Reprod. Advance Access originally published online on September 3, 2004
Human Reproduction 2004 19(12):2913-2918; doi:10.1093/humrep/deh514
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Mouse oocyte meiotic resumption and polar body extrusion in vitro are differentially influenced by FSH, epidermal growth factor and meiosis-activating sterol
1 TECNOBIOS Procreazione, Bologna, 40125, 2 Department of Biomedical Sciences and Technologies, 3 Department of Experimental Medicine, University of L'Aquila, L'Aquila, 67010, Italy, 4 Novo Nordisk A/S, Copenhagen, 2820, Denmark, 5 University of Bologna, 40125, Bologna, Italy and 6 Department of Obstetrics & Gynaecology, University of Sydney, Sydney, NSW 2145, Australia
7 To whom correspondence should be addressed at: Department of Sciences and Biomedical Technologies, University of L'Aquila, Via Vetoio, Loc. Coppito, 67010 Coppito, L'Aquila, Italy. Email: cecconi{at}univaq.it
BACKGROUND: In this study, we compared the relative ability of FSH (100 mIU/ml), epidermal growth factor (EGF) (10 ng/ml), and follicular-fluid meiosis-activating sterol (FF-MAS, 10 µmol/l) to induce meiotic resumption and polar body I (PBI) extrusion in mouse oocytes. METHODS: Cumulus-enclosed oocytes (CEO) were co-incubated with meiosis-arresting agents, including 4 mmol/l hypoxanthine (Hx), 0.3 mmol/l dibutyryl cAMP (dbcAMP), and 8.5 µmol/l cilostamide, a selective inhibitor of the oocyte-specific phosphodiesterase 3 (PDE 3). RESULTS: In Hx-treated oocytes, FSH, EGF and FF-MAS induced meiosis resumption at very high rates, but only FSH and EGF also promoted PBI extrusion with high frequency. In experiments conducted in the presence of dbcAMP, FF-MAS was unable to promote an increase in germinal vesicle breakdown (GVBD) rate, whereas FSH and EGF generated a response similar to the Hx groups. Neither FSH, EGF nor FF-MAS caused any change in the meiotic status of CEO when meiotic arrest at the germinal vesicle (GV) stage was maintained by cilostamide. In the presence of Hx, naked oocytes (NkO) co-cultured with their cumulus cells were able to respond to the GVBD-inducing effect of FSH and EGF by resuming meiosis at high rate. CONCLUSIONS: Collectively, these results indicate that: (i) a signal triggered in cumulus cells by either FSH or EGF, but not necessarily coincident with FF-MAS, may contribute to meiotic maturation, supporting GVBD and extrusion of PBI; (ii) the transmission of this signal can occur in a paracrine fashion, at least with reference to the breakdown of the GV. It also appears that concomitant regulation of intra-oocyte cAMP degradation is a prerequisite for meiosis resumption.
Key words: cumulus cells/FSH/meiosis/oocyte development
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