How relevant is the mouse model for understanding human sex determination?
The mouse is the most widely used model organism for studying mammalian gonadal sex determination and related human disorders. However, a systematic and comprehensive comparison of human and mouse sex determination processes is lacking. Here, we performed an interspecies comparative analysis of the single-cell transcriptomic atlas of gonadal sex determination in mice and humans. Our results revealed major transcriptomic differences in each of the major cell types between human and mouse gonads. Only a small fraction of these genes shared a comparable expression profile, often genes known to be essential for gonadal sex determination. While the most differentiated gonadal cell types share similar transcriptomic signatures between humans and mice, poorly differentiated cells, such as somatic progenitors, show more divergent profiles. Ultimately, these comparisons will identify the genes and pathways for which the mouse is a suitable model to study human gonadal abnormalities and optimise the use of animal models.
Authors
- Susana M. Chuva de Sousa Lopes (ORCID: https://orcid.org/0000-0003-3866-2803)
- Frédéric Chalmel (ORCID: https://orcid.org/0000-0002-0535-3628)
- Pauline Sararols (ORCID: https://orcid.org/0000-0001-8063-1096)
- Antoine D. Rolland (ORCID: https://orcid.org/0000-0002-9758-4406)
- Serge Nef (ORCID: https://orcid.org/0000-0001-5462-0676)
- Chloé Mayère (ORCID: https://orcid.org/0000-0002-9254-4886)
- Séverine Mazaud‐Guittot (ORCID: https://orcid.org/0000-0003-0566-4124)
- Cyril Djari (ORCID: https://orcid.org/0000-0001-7666-9024)
- Violaine Regard (ORCID: https://orcid.org/0000-0002-9827-0417)
- Aurélie Lardenois (ORCID: https://orcid.org/0000-0003-1339-104X)
- Francisco Brito (ORCID: https://orcid.org/0000-0003-1404-9799)
- Sylwia Czukiewska (ORCID: https://orcid.org/0000-0001-9151-9008)
- Yasmine Neirijnck (ORCID: https://orcid.org/0000-0001-7236-8451)
- Françoise Kühne
Institutions
- University of Geneva (CH)
- Leiden University (NL)
- Inserm (FR)
- École des Hautes Études en Santé Publique (FR)
- Institut de Recherche en Santé, Environnement et Travail (FR)
- Université de Rennes (FR)
Publication Details
- Journal
- International Journal of Biological Sciences
- Published
- 2025-10-15
- DOI
- https://doi.org/10.7150/ijbs.90231
- Primary Topic
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Type
- article
- Field-Weighted Citation Impact
- 0.00