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Complete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster

Alicia Hurtado1,2,3, Irene Mota-Gómez2, Miguel Lao1

  • 1Department of Genetics and Institute of Biotechnology, Labs. 127 and A105, Centre for Biomedical Research, University of Granada, Armilla, Granada, Spain.

Nature Communications
|May 7, 2024
PubMed

Insights

Deletion of the microRNA-17~92 cluster causes male-to-female sex reversal in XY mice. This highlights microRNAs

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Mammalian sex determination relies on gene cascades in gonads.
  • SRY gene triggers testicular development; its absence leads to ovarian differentiation.
  • The role of non-coding RNA in sex determination is largely unknown.

Purpose of the Study:

  • To investigate the role of microRNA regulation in mammalian sex determination.
  • To determine the function of the miR-17~92 cluster in gonad development.

Main Methods:

  • Generation of XY mice lacking the miR-17~92 microRNA cluster.
  • Analysis of gonad development and gene expression in knockout mice.
  • Bioinformatic prediction of miR-17~92 targets.

Main Results:

  • miR-17~92 deletion caused complete male-to-female sex reversal in XY mice.
  • Sry expression was delayed, and Sertoli cell differentiation was impaired in XY knockout gonads.
  • Gonads developed as ovaries with a transient state of sex ambiguity.

Conclusions:

  • MicroRNAs, specifically miR-17~92, are crucial for mammalian sex determination.
  • This microRNA cluster regulates Sry expression timing and Sertoli cell differentiation.
  • MicroRNAs are key regulators of gene networks controlling gonad development.

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