TRPV4 associates environmental temperature and sex determination in the American alligator

Sci Rep. 2015 Dec 18:5:18581. doi: 10.1038/srep18581.

Abstract

Temperature-dependent sex determination (TSD), commonly found among reptiles, is a sex determination mode in which the incubation temperature during a critical temperature sensitive period (TSP) determines sexual fate of the individual rather than the individual's genotypic background. In the American alligator (Alligator mississippiensis), eggs incubated during the TSP at 33 °C (male producing temperature: MPT) yields male offspring, whereas incubation temperatures below 30 °C (female producing temperature: FPT) lead to female offspring. However, many of the details of the underlying molecular mechanism remains elusive, and the molecular link between environmental temperature and sex determination pathway is yet to be elucidated. Here we show the alligator TRPV4 ortholog (AmTRPV4) to be activated at temperatures proximate to the TSD-related temperature in alligators, and using pharmacological exposure, we show that AmTRPV4 channel activity affects gene expression patterns associated with male differentiation. This is the first experimental demonstration of a link between a well-described thermo-sensory mechanism, TRPV4 channel, and its potential role in regulation of TSD in vertebrates, shedding unique new light on the elusive TSD molecular mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alligators and Crocodiles / growth & development
  • Alligators and Crocodiles / metabolism*
  • Animals
  • Aromatase / genetics
  • Aromatase / metabolism
  • Calcium / metabolism
  • Embryo, Nonmammalian / metabolism
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • HEK293 Cells
  • Humans
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Male
  • Mullerian Ducts / drug effects
  • Mullerian Ducts / pathology
  • Oocytes / metabolism
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • Sex Determination Processes / drug effects
  • Sex Determination Processes / physiology*
  • Sulfonamides / pharmacology
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Temperature*
  • United States
  • Xenopus / growth & development
  • Xenopus / metabolism

Substances

  • N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide
  • RN 1734
  • Receptors, Peptide
  • Receptors, Transforming Growth Factor beta
  • SOX9 Transcription Factor
  • Sulfonamides
  • TRPV Cation Channels
  • anti-Mullerian hormone receptor
  • Aromatase
  • Leucine
  • Calcium