The Role and Mechanism of Nodal in Regulation of Oocyte Maturation in Zebrafish

Zebrafish is beneficial to study endocrine and paracrine pathways conserved among vertebrates, such as follicle development and oocyte maturation. Luteinizing hormone (LH) induces maturation inducing hormone (MIH) from the ovary to initiate oocyte maturation. Late vitellogenic (stage IIIb) follicles respond to these hormone signals to undergo oocyte maturation. Nodal, a member of the TGF-β superfamily, plays an important role in embryo development. Stage IIIb follicles subjected to Nodal treatment showed oocyte maturation induced in a dose- and time-dependent manner. In vivo, ndr2+/- knockouts had higher progesterone levels but lower 17a-HP, suggesting ndr2 promotes progesterone to 17a-HP conversion. To determine if Nodal regulates the cAMP pathway, regulation of cAMP responsive element binding proteins (CREB) were examined. Treatment of follicles with Nodal resulted in increased CREB-1a levels in oocytes. This study demonstrates that Nodal promotes zebrafish oocyte maturation, probably by upregulating 17a-HP production in follicular cells and downregulating CREB-5a expression in oocytes.