Zebrafish Androgen Receptor is Required for Spermatogenesis and Maintenance of Ovarian Function
Overview
Affiliations
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 in reproductive development, particularly spermatogenesis. Here, we investigated the role of in zebrafish using CRISPR/Cas9 gene targeting technology. Targeted disruption of in zebrafish increases the number of female offspring and increases offspring weight. In addition, -null male zebrafish have female secondary sex characteristics. More importantly, targeted disruption of 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 -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 is required for spermatogenesis and maintenance of ovarian function, which confirms evolutionarily conserved functions of in vertebrates, as well as indicates that -null zebrafish are a suitable model for studying pathologic mechanisms related to androgen disorders.
Wu K, Yue Y, Zhou L, Zhang Z, Shan H, He H Commun Biol. 2025; 8(1):371.
PMID: 40044757 PMC: 11882886. DOI: 10.1038/s42003-025-07719-3.
Pathirajage K, Rajapaksa G Sci Rep. 2024; 14(1):24503.
PMID: 39424622 PMC: 11489671. DOI: 10.1038/s41598-024-73538-x.
Xiao H, Wang L, Yan S, Ma H, Xu Z, Wang F Commun Biol. 2024; 7(1):1154.
PMID: 39284885 PMC: 11405705. DOI: 10.1038/s42003-024-06853-8.
Orlova S, Ruzina M, Emelianova O, Sergeev A, Chikurova E, Orlov A Genes (Basel). 2024; 15(6).
PMID: 38927661 PMC: 11202958. DOI: 10.3390/genes15060726.
Direct male development in chromosomally ZZ zebrafish.
Wilson C, Batzel P, Postlethwait J Front Cell Dev Biol. 2024; 12:1362228.
PMID: 38529407 PMC: 10961373. DOI: 10.3389/fcell.2024.1362228.