Nuclear androgen receptor regulates testes organization and oocyte maturation in zebrafish

Androgens act through the nuclear androgen receptor (AR) to regulate gonad differentiation and development. In mice, AR is required for spermatogenesis, testis development and formation of external genitalia in males and oocyte maturation in females. However, the extent to which these phenotypes are conserved in nonmammalian vertebrates is not well understood, because mutations in AR have not been generated in any other species. Here, we generate zebrafish with a mutation in the ar gene and examine the role of AR on sexual differentiation and gonad development. We find that zebrafish AR is not required for male sexual differentiation, since a portion of ar mutants develop a testis. However, we show that in zebrafish, as in mice, AR is required for the development of secondary sexual characteristics and for proper organization of the testis in males and for oocyte maturation in females. Additionally, we find that zebrafish ar mutant males have functional, mature sperm present in their testis, but are infertile due to an inability to release sperm. These findings suggest that AR is required for male sexual development and fertility, but not essential for sexual differentiation in zebrafish. The ar mutant we developed will be useful for modeling human endocrine function in zebrafish.