Clelland, E., Kohli, G., Campbell, R.K., Sharma, S., Shimasaki, S., and Peng, C. (2006) Bone morphogenetic protein 15 in the zebrafish ovary: cDNA cloning, genomic organization, tissue distribution and role in oocyte maturation. Endocrinology. 147(1):201-209.
Bone morphogenetic protein-15 (BMP-15) is a member of the transforming growth factor-beta family known to regulate ovarian functions in mammals. The structure and function of BMP-15 in lower vertebrates are less known. In this study, we cloned the zebrafish BMP-15 (zfBMP-15) cDNA and depicted its genomic organization. The zfBMP-15 cDNA encodes a protein of 384 amino acids. The mature protein has 46-51% sequence identities to fugu, chicken, and mammalian BMP-15. It also shares 38-46% homology with growth and differentiation factor (GDF)-9 in fishes, chicken and mammals. Phylogenetic analysis further confirms that the zfBMP-15 is most closely related to BMP-15 from other species while the GDF-9 peptides from fish to mammals form a distinct branch. Comparison of zfBMP-15 cDNA with zebrafish genome database revealed that zfBMP-15 is encoded by a gene with two exons and one intron, located on chromosome 6. BMP-15 mRNA is expressed in the ovary and testis, and to a lesser extent, in brain, liver, gut, heart and muscle. Real-time PCR revealed that BMP-15 is expressed in follicles at all stages of development with no significant changes over the course of folliculogenesis. Using in situ hybridization and immunocytochemistry, we detected BMP-15 in both oocytes and follicular cells. Incubation of follicles with antiserum against zfBMP15 increased oocyte maturation, while incubation with recombinant human BMP-15 suppressed human chorionic gonadotropin-induced oocyte maturation. These findings suggest that BMP-15 plays a role in regulating gonadal functions in fish, in particular oocyte maturation.