The role and mechanism of BMP-15, activin and TGF-beta in regulating zebrafish oocyte maturation

The transforming growth factor-beta (TGF-beta) superfamily is a large group of growth and differentiation factors that have important functions in many physiological processes, including reproduction. We previously reported that several members of the TGF-beta superfamily, including activin-A, bone morphogenetic protein-15 (BMP-15) and TGF-beta1, regulate oocyte maturation in zebrafish. The aim of this study was to further examine the functions and mechanisms of these growth factors in regulating zebrafish oocyte maturation. Overexpression of BMP-15 reduced the effect of activin-A on oocyte maturation. Inhibition of BMP-15 function or expression increased oocyte maturation. TGF-beta1 suppressed activin-A-, as well as BMP-15 antiserum-induced oocyte maturation. Knockdown of smad2 completely blocked activin-A-induced oocyte maturation and significantly decreased basal and gonadotropin-induced oocyte maturation. Membrane progestin receptors (mPRalpha and mPRbeta) are key mediators of maturation-inducing hormone. We found that activin-A stimulated, while BMP-15 and TGF-beta1 suppressed mPRbeta protein expression. Activin-A also induced the expression of mPRalpha. These findings suggest that BMP-15, activin-A, and TGF-beta1 exert their regulatory effects on oocyte maturation in part by regulating mPR expression.