Nuclear Androgen Receptor Regulates Testes Organization and Oocyte Maturation in Zebrafish

Area of Science:

• Endocrinology
• Developmental Biology
• Genetics

Background:

• Androgens, acting via the androgen receptor (AR), are vital for mammalian gonad development and function.
• The conserved role of AR in nonmammalian vertebrates, particularly in sexual determination and gonadogenesis, remains incompletely understood.

Purpose of the Study:

• To investigate the function of the androgen receptor (AR) in sexual determination and gonad development in zebrafish.
• To characterize the phenotype of zebrafish with a mutation in the ar gene (aruab105/105).

Main Methods:

• Generation of zebrafish with a knockout mutation in the ar gene (aruab105/105).
• Phenotypic analysis of mutant zebrafish, including sexual determination, gonad morphology, and gametogenesis.
• Gene expression analysis of key sexually dimorphic genes in mutant gonads.

Main Results:

• Zebrafish AR regulates male sexual determination; the majority of ar mutants developed ovaries and female secondary sexual characteristics.
• Mutant males that developed testes showed structural disorganization, impaired sperm production, and infertility, indicating AR's necessity for testis development and fertility.
• AR is essential for female oocyte maturation and fecundity, with mutants exhibiting ovaries rich in immature oocytes.
• Sexually dimorphic gene expression was altered in mutant gonads, with upregulation of ovary-enriched genes in mutant testes and testis-enriched genes in mutant ovaries.

Conclusions:

• Zebrafish AR plays a critical role in male sexual determination, testis development, and fertility.
• AR is essential for oocyte maturation and fecundity in female zebrafish.
• These findings demonstrate AR's role in regulating sexually dimorphic gene expression and suggest the zebrafish ar mutant is a valuable model for studying human endocrine function.