Transforming growth factor‐alpha augments meiotic maturation of cumulus cell‐enclosed mouse oocytes

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Abstract
Growth factors have been shown to play an important role in the regulation of ovarian function. In this study, we examined the effects of transforming growth factor‐α (TGF‐α) on the meiotic maturation of immature mouse oocytes in vitro. Cumulus cell‐enclosed oocytes were exposed to TGF‐α with or without the meiotic inhibitor hypoxanthine (HX), and oocyte maturation was assessed by germinal vesicle breakdown (GVBD). Likewise, mechanically denucded oocytes were examined for GVBD following exposure to HX and TGF‐α. When cumulus cell‐enclosed oocytes were exposed to TGF‐α (1 μg/ml) in the presence of HX (4 mM), an increrase in GVBD was observed first after 5 hours of culture. Maximal stimulation was reached at 24 hours when 70% of the oocytes underwent maturation in the presence of TGF‐α and HX as compared to 33% with HX only. Concentrations of TGF‐α as low as 0.1 ng/ml produced a similar stimulatory response after 24 hours of culture. Spontaneous maturation in the presence of TGF‐α, but without HX, was also enhanced. The stimulation of GVBD by TGF‐α showed an increase over time both with and without HX. When denuded oocytes were exposed to TGF‐α in the presence of HX, no effect was observed. Our results suggest that TGF‐α is a potent stimulator of mouse oocyte maturation in vitro and that is effect is mediated by the surrounding cumulus cells. In view of the established presence and action of TGF‐α in the intact ovary, these studies indicate that TGF‐α may be part of an intricate system regulating the latter stages of maturation of oocytes during follicular development in vivo.