ZFIN ID: ZDB-PUB-171223-7
Nuclear androgen receptor regulates testes organization and oocyte maturation in zebrafish
Crowder, C.M., Lassiter, C.S., Gorelick, D.A.
Date: 2017
Source: Endocrinology   159(2): 980-993 (Journal)
Registered Authors: Crowder, Camerron M., Gorelick, Daniel, Lassiter, Christopher S.
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Nucleus/metabolism
  • Embryo, Nonmammalian
  • Female
  • Fertility/genetics
  • Male
  • Oogenesis/genetics*
  • Receptors, Androgen/genetics
  • Receptors, Androgen/physiology*
  • Sex Differentiation/genetics*
  • Spermatogenesis/genetics*
  • Testis/cytology*
  • Testis/growth & development*
  • Testis/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/growth & development
PubMed: 29272351 Full text @ Endocrinology
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 non-mammalian vertebrates is not well understood. Here, we generate zebrafish with a mutation in the ar gene (aruab105/105) and examine the role of AR on sexual determination and gonad development. We find that zebrafish AR regulates male sexual determination, since the majority of aruab105/105 mutant embryos developed ovaries and display female secondary sexual characteristics. The small percentage of mutants that developed testes displayed female secondary sexual characteristics, exhibited structurally disorganized testes and were unable to release or produce normal levels of sperm, demonstrating that AR is necessary for zebrafish testis development and fertility. In females, we find that AR regulates oocyte maturation and fecundity. Aruab105/105 mutant females developed ovaries filled primarily with immature stage I oocytes and relatively few mature stage III oocytes. Two genes whose expression is enriched in wild-type ovaries compared to testes (cyp19a1a, foxl2a) were upregulated in ar mutant testes, while two genes enriched in testes (amh, dmrt1) were upregulated in ar mutant ovaries. These findings demonstrate that AR regulates sexual determination, testes development and oocyte maturation and suggest that AR regulates sexually dimorphic gene expression. The ar mutant we developed will be useful for modeling human endocrine function in zebrafish.