Endocrine Abstracts

Sex development in zebrafish is highly plastic, making this species an ideal model for investigation of endocrine disruption and gonadal development and function. However, the hormonal regulation of these processes in zebrafish is poorly understood. We have used a model of androgen and glucocorticoid deficiency to explore these processes. In humans, ferredoxin (FDX1) is an electron-providing cofactor required for steroid biosynthesis. The zebrafish homologue of FDX1, fdx1b, has a crucial androgen biosynthesis. Fdx1b mutant zebrafish are profoundly androgen and glucocorticoid deficient. We have analysed the phenotype of adult fdx1b mutant zebrafish to investigate the role of steroids in sex development and gonadal differentiation. Fdx1b mutants exhibit feminised secondary sex characteristics but may possess either testes or ovaries, both sexes are sterile. Histological investigation showed abnormal seminiferous tubule structure and disorganisation of fdx1b mutant testes, compared to those of wild-type siblings. To investigate mechanisms behind testicular disruption and sterility we measured expression of genes regulating testicular development or spermatogenesis. We observed downregulation of pro-testis gene sox9a, and igf3, a key factor for spermatogonial proliferation and differentiation, in fdx1b mutant testes. The mechanism behind female infertility remains unclear and is currently under investigation however misregulation of several genes involved in female development has been detected. Whilst androgens regulate some secondary sex characteristics, they do not promote testis differentiation, as mutants developed distinct ovaries or testes. However, it is clear that androgens have an important role in development, maturation, organisation and function of both male and female gonads, since adult males and females were sterile. Taken together, our observations provide novel insights into the roles of androgens in these processes. We anticipate that these insights will support development of model organisms to study the interplay of genetic factors and environment in disorders of sex development.