Role of activin, transforming growth factor-beta and bone morphogenetic protein 15 in regulating zebrafish oocyte maturation.

The transforming growth factor-beta (TGF-beta) superfamily is a large group of peptide 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. First, the interaction among three regulators was examined. Overexpression of BMP-15 reduced the effect of activin-A on oocyte maturation. Inhibition of BMP-15 function or expression increased oocyte maturation but had no additive effect with activin-A. TGF-beta1 suppressed activin-A-, as well as BMP-15 antiserum-induced oocyte maturation. Second, the role of Smad 2, an intracellular mediator of activin and TGF-beta, in oocyte maturation was investigated. Western blot analysis revealed that both activin-A and TGF-beta1 activate Smad2 in zebrafish follicles. Injection of morpholino antisense olignucleotides against Smad2 into oocytes reduced Smad2 expression and completely blocked activin-A-induced oocyte maturation. Knockdown of Smad 2 also significantly decreased basal and hCG-induced oocyte maturation. These findings suggest that activin-A, TGF-beta1, and BMP-15 may target common gene(s) to regulate oocyte maturation and demonstrate that Smad2 plays an important role in oocyte maturation.