Transforming Growth Factor-β Stimulates Meiotic Maturation of the Rat Oocyte

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Abstract
The effect of transforming growth factor-.beta. (TGF.beta.) on meiotic maturation was analyzed in oocytes from immature rats treated with PMSG. TGF.beta. accelerated the maturation of both follicle-enclosed oocytes and cumulus-oocyte complexes, as measured by an increase in the percentage of oocytes with germinal vesicle breakdown. Concentrations of the growth factor as low as 1 PM (25 pg/ml) increased oocyte maturation by 50% above control values and 100 PM TGF.beta. caused a maximal 2-fold rise in the maturation rate. Germinal vesicle breakdown was significantly increased by TGF.beta. during the first 4 h of incubation and stimulatory effects were observed as early as 1 h. However, by 8 h over 90% of the oocytes showed maturation in the absence or presence of TGF.beta., indicating that the growth factor enhanced the spontaneous rate of oocyte development TGF.beta. had no effect in denuded oocytes, demonstrating that the growth factor altered maturation through an action on the surrounding cumulus cells. Oocyte maturation was not accelerated by TGF.beta. in the presence of inhibitors of germinal vesicle breakdown, such as cAMP and hypoxanthine. Other growth factors, including IGF-I (50 ng/ml) and IGF-II (50 ng/ml), also stimulated oocyte maturation, while platelet-derived growth factor (100 ng/ml)and insulin (1 .mu.g/ml) had minimal effects on germinal vesicle breakdown. Although epidermal growth factor (EGF; 100 ng/ml) also increased the maturation of oocytes, lower concentrations of TGF.beta. (1-10 PM) suppressed EGF action by up to 30%. TGF.beta., EGF, and insulin-like growth factors had minimal effects on cAMP production by cumulus-oocyte complexes. These results demonstrate that TGF.beta. and other growth factors are potent in vitro stimulators of oocyte maturation in the rat. Such effects of growth factors in vivo, in the presence of endogenous follicular factors and gonadotropic hormones, may regulate the selection and meiotic maturation of oocytes during follicular development. The rapidity of growth factor action in the oocyte provides a defined model to study signal transduction pathsway of growth factors in relationship to their biological activity.