A Hormone That Lost Its Receptor: Anti-Müllerian Hormone (AMH) in Zebrafish Gonad Development and Sex Determination

Yan, Y.L., Batzel, P., Titus, T., Sydes, J., Desvignes, T., Bremiller, R., Draper, B., Postlethwait, J.H.
Genetics   213(2): 529-553 (Journal)
Registered Authors
BreMiller, Ruth, Draper, Bruce, Postlethwait, John H., Titus, Tom A., Yan, Yi-Lin
PGC, female fertility, germ cells, gonad development, male fertility
MeSH Terms
  • Animals
  • Anti-Mullerian Hormone/genetics*
  • Female
  • Genitalia, Female/growth & development*
  • Gonads/growth & development
  • Mullerian Ducts/growth & development
  • Ovarian Follicle/growth & development
  • Ovary/growth & development
  • RNA-Seq
  • Receptors, Peptide/genetics
  • Receptors, Transforming Growth Factor beta/genetics
  • Sex Determination Processes*
  • Zebrafish/genetics*
  • Zebrafish/growth & development
31399485 Full text @ Genetics
Fetal mammalian testes secrete Amh (Anti-Müllerian hormone), which inhibits female reproductive tract (Müllerian duct) development. Amh also derives from mature mammalian ovarian follicles, which marks oocyte reserve and characterizes PCOS (polycystic ovarian syndrome). Zebrafish (Danio rerio) lacks Müllerian ducts and the Amh receptor gene amhr2 but, curiously, retains amh To discover the roles of Amh in the absence of Müllerian ducts and the ancestral receptor gene, we made amh null alleles in zebrafish. Results showed that normal amh prevents female-biased sex ratios. Adult male amh mutants had enormous testes, half of which contained immature oocytes, demonstrating that Amh regulates male germ cell accumulation and inhibits oocyte development or survival. Mutant males formed sperm ducts and some produced a few offspring. Young female mutants laid a few fertile eggs, so they also had functional sex ducts. Older amh mutants accumulated non-vitellogenic follicles in exceedingly large but sterile ovaries, showing that Amh helps control ovarian follicle maturation and proliferation. RNA-seq data partitioned 21-day post-fertilization (dpf) juveniles into two groups that each contained mutant and wild type fish. Group21-1 up-regulated ovary genes compared to Group21-2, which were likely developing as males. By 35dpf, transcriptomes distinguished males from females and, within each sex, mutants from wild types. In adult mutants, ovaries greatly under-expressed granulosa and theca genes and testes under-expressed Leydig cell genes. These results show that ancestral Amh functions included development of the gonadal soma in ovaries and testes and regulation of gamete proliferation and maturation. A major gap in our understanding is the identity of the gene encoding a zebrafish Amh receptor; we show here that the loss of amhr2 is associated with the breakpoint of a chromosome rearrangement shared among cyprinid fishes.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes