Zebrafish androgen receptor is required for spermatogenesis and maintenance of ovarian function

Abstract

The androgen receptor (AR) is a nuclear receptor protein family member and inducible transcription factor that modulates androgen target gene expression. Studies using a mouse model confirmed the need for ar in reproductive development, particularly spermatogenesis. Here, we investigated the role of ar in zebrafish using CRISPR/Cas9 gene targeting technology. Targeted disruption of ar in zebrafish increases the number of female offspring and increases offspring weight. In addition, ar-null male zebrafish have female secondary sex characteristics. More importantly, targeted disruption of ar in zebrafish causes male infertility via defective spermatogenesis and female premature ovarian failure during growth. Mechanistic assays suggest that these effects are caused by fewer proliferated cells and more apoptotic cells in ar-null testes. Moreover, genes involved in reproductive development, estradiol induction and hormone synthesis were dys-regulated in testes and ovaries and the reproductive-endocrine axis was disordered. Our data thus suggest that the zebrafish ar is required for spermatogenesis and maintenance of ovarian function, which confirms evolutionarily conserved functions of ar in vertebrates, as well as indicates that ar-null zebrafish are a suitable model for studying pathologic mechanisms related to androgen disorders.