Gamete Biology

Meiosis-Activating Sterol Synthesis in Rat Preovulatory Follicle: Is It Involved in Resumption of Meiosis?

Abstract
Meiosis activating sterols (MAS) were shown to overcome the inhibitory effect of hypoxanthine on spontaneous maturation of mouse oocytes and were suggested to mediate the stimulation of meiosis by gonadotropins. Follicular fluid (FF)-MAS is synthesized by cytochrome P450 lanosterol 14-demethylase (LDM). Follicular LDM was preferentially localized in oocytes by immunohistochemistry. Using [³H] acetate or R-[5-³H] mevalonate as precursors and HPLC and TLC separation we have measured the concentrations of de novo-synthesized lanosterol, FF-MAS and cholesterol in rat Graafian follicles, cumulus oocyte complexes (COCs), and denuded oocytes (DOs) treated with LH, AY-9944 (an inhibitor of 14-reductase which was anticipated to increase FF-MAS levels by inhibiting its metabolism), or both after 8 h of culture. In follicles both LH and AY-9944 increased the accumulation of FF-MAS as compared to controls. In COCs AY-9944 caused a marked increase in FF-MAS, but we were unable to detect accumulation of FF-MAS in DOs. Neither the endogenous increases in FF-MAS accumulation nor the addition of FF-MAS to the culture medium could overcome the inhibition of resumption of meiosis by phospodiesterase (PDE) inhibitors. Compared to LH-induced resumption of meiosis in follicles, that induced by AY-9944 was much delayed. These results question any role of FF-MAS as an obligatory mediator of LH activity on germinal vesicle breakdown. The discrepancy between the positive staining for LDM in oocytes and our inability to detect de novo synthesized FF-MAS in denuded oocytes may be related to the sensitivity of the methodology employed and the number of oocytes used or a deficiency in LDM synthetic activity in such oocytes. Further studies are required to confirm any of these alternatives.

Key words: Gamete Biology • Cumulus cells • Follicle • Meiosis • Oocyte development

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