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Peer-reviewedCC BYScience Advances

DMRT1 is required at two steps of ovarian differentiation in rabbits

  • Emilie Dujardin1,2
  • Francis Poulat3
  • Ivan Barberá Aura4
  • Aurélie Dewaele1,2
  • Marjolaine André1,2
  • Jennifer McKey5
  • Stéphanie Le Gras6
  • Anne Frambourg1,2
  • Luc Jouneau1,2
  • Darío G. Lupiáñez4
  • Béatrice Mandon-Pépin1,2
  • Eric Pailhoux1,2
6 affiliations
  1. 1BREED, Université Paris-Saclay, UVSQ, INRAE, 78350 Jouy-en-Josas, France.
  2. 2BREED, École Nationale Vétérinaire d’Alfort, 94700 Maisons-Alfort, France.
  3. 3Institute of Human Genetics, CNRS UMR9002, University of Montpellier, 34396 Montpellier, France.
  4. 4Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide, Junta de Andalucía, Consejo Superior de Investigaciones Científicas, Seville, Spain.
  5. 5Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  6. 6GenomEast platform, IGBMC, 67404 Illkirch, France.
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Abstract

The transcription factor Doublesex and Mab-3 Related Transcription Factor 1 (DMRT1) is essential for testis differentiation and male fertility, but less is known about its potential involvement in ovarian differentiation. In mice, Dmrt1-/- females are fertile, although they show a reduction of Stra8 expression. Using our DMRT1 mutant rabbit model, we analyzed ovarian differentiation when DMRT1 expression is abolished. First, we observed that during early gonadal development, DMRT1-/- gonads display a specific transcriptome different from control ovaries and control testes. Second, we assessed the infertility phenotype of mutant females. DMRT1 is highly expressed in germ cells until meiosis initiation, and its disruption leads to a down-regulation of key genes involved in the meiotic process. Chromatin immunoprecipitation sequencing data highlighted that DMRT1 can bind these genes in the rabbit ovary. Our study using the rabbit model shows that in addition to its role in testicular differentiation, DMRT1 has two important functions in ovarian differentiation: an initial involvement in the differentiation of somatic cells and a pivotal role in the differentiation of germ cells. Our data suggested that DMRT1 could be considered in human health as a gene necessary for female fertility.

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Cite

BibTeXRIS
BibTeX
@article{dujardin2026dmrt1,
  title = {{DMRT1 is required at two steps of ovarian differentiation in rabbits}},
  author = {Emilie Dujardin and Francis Poulat and Ivan Barberá Aura and Aurélie Dewaele and Marjolaine André and Jennifer McKey and Stéphanie Le Gras and Anne Frambourg and Luc Jouneau and Darío G. Lupiáñez and Béatrice Mandon-Pépin and Eric Pailhoux},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeh1087},
  url = {https://www.science.org/doi/10.1126/sciadv.aeh1087},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - DMRT1 is required at two steps of ovarian differentiation in rabbits
AU  - Emilie Dujardin
AU  - Francis Poulat
AU  - Ivan Barberá Aura
AU  - Aurélie Dewaele
AU  - Marjolaine André
AU  - Jennifer McKey
AU  - Stéphanie Le Gras
AU  - Anne Frambourg
AU  - Luc Jouneau
AU  - Darío G. Lupiáñez
AU  - Béatrice Mandon-Pépin
AU  - Eric Pailhoux
PY  - 2026
DA  - 2026/10/21
JO  - Science Advances
DO  - 10.1126/sciadv.aeh1087
UR  - https://www.science.org/doi/10.1126/sciadv.aeh1087
AB  - The transcription factor Doublesex and Mab-3 Related Transcription Factor 1 (DMRT1) is essential for testis differentiation and male fertility, but less is known about its potential involvement in ovarian differentiation. In mice, Dmrt1-/- females are fertile, although they show a reduction of Stra8 expression. Using our DMRT1 mutant rabbit model, we analyzed ovarian differentiation when DMRT1 expression is abolished. First, we observed that during early gonadal development, DMRT1-/- gonads display a specific transcriptome different from control ovaries and control testes. Second, we assessed the infertility phenotype of mutant females. DMRT1 is highly expressed in germ cells until meiosis initiation, and its disruption leads to a down-regulation of key genes involved in the meiotic process. Chromatin immunoprecipitation sequencing data highlighted that DMRT1 can bind these genes in the rabbit ovary. Our study using the rabbit model shows that in addition to its role in testicular differentiation, DMRT1 has two important functions in ovarian differentiation: an initial involvement in the differentiation of somatic cells and a pivotal role in the differentiation of germ cells. Our data suggested that DMRT1 could be considered in human health as a gene necessary for female fertility.
SN  - 2375-2548
ER  -