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Human Reproduction, Vol. 18, No. 1, 122-129, January 2003
© 2003 European Society of Human Reproduction and Embryology

Clinical Investigations

Physiology of meiosis-activating sterol: endogenous formation and mode of action

Christian Grøndahl1,3, Jens Breinholt1, Philip Wahl1, Anthony Murray1, Thomas Høst Hansen1, Inger Færge1, Carsten E. Stidsen1, Kirsten Raun1 and Christa Hegele-Hartung2

1 Fertility Team, Research and Development, Novo Nordisk A/S, Copenhagen, Denmark and 2 Research Laboratories, Schering AG, Berlin, Germany 3 To whom correspondence should be addressed at: Fertility Team, Novo Nordisk A/S, Sauntesvej 13, DK-2820 Gentofte, Denmark. e-mail: chgr{at}novonordisk.com

BACKGROUND: In the context of mammalian oocyte maturation, it has been suggested that intermediates of cholesterol biosynthesis may represent the physiological signal that instructs the oocyte to reinitiate meiosis. METHODS: Endogenous levels of follicular fluid meiosis-activating sterol (FF-MAS) were monitored in rabbit ovarian tissue, and the influence of exogenous gonadotrophins on sterol formation was assessed. The involvement of cAMP in FF-MAS-induced versus spontaneous oocyte maturation in vitro in mice was also investigated, as was the direct microinjection of FF-MAS into mouse oocytes. RESULTS: Levels of FF-MAS in rabbit ovaries were significantly elevated 1 h after hCG/LH induction and remained so for 4 and 12 h after induction. In naked oocytes undergoing spontaneous maturation, a significant decrease in cAMP was detected after 30 min of culture. However, FF-MAS-mediated induction of oocyte maturation in hypoxanthine-arrested naked oocytes was not associated with any detectable decrease in intracellular cAMP levels. Microinjected FF-MAS failed to induce any noticeable meiosis. CONCLUSIONS: A rapid increase in FF-MAS level occurred in vivo in the rabbit ovary in response to LH, and clear differences were seen in the cAMP pattern during spontaneous and induced oocyte maturation in mice.

Key words: FF-MAS/follicle/gonadotrophins/IVM/oocyte


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