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How relevant is the mouse model for understanding human sex determination?
Francisco Brito1, Chloé Mayère1, Aurélie Lardenois2
1Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
International Journal of Biological Sciences
|November 24, 2025
Summary
Mice and humans show significant transcriptomic differences in gonadal sex determination, particularly in progenitor cells. This study highlights where mouse models are suitable for studying human gonadal development and disorders.
Area of Science:
- Developmental Biology
- Comparative Genomics
- Genetics
Background:
- The mouse is a key model organism for studying mammalian gonadal sex determination.
- A comprehensive comparison between human and mouse sex determination processes is currently lacking.
- Understanding these differences is crucial for interpreting mouse model studies of human reproductive health.
Purpose of the Study:
- To conduct a systematic, interspecies comparative analysis of single-cell transcriptomic data for gonadal sex determination in humans and mice.
- To identify conserved and divergent gene expression profiles across major cell types.
- To evaluate the suitability of the mouse as a model for human gonadal development and disorders.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) data from human and mouse gonads.
- Comparative transcriptomic analysis of cell types.
- Identification of differentially expressed genes and conserved pathways.
Main Results:
- Major transcriptomic differences were observed in most cell types between human and mouse gonads.
- Conserved gene expression profiles were mainly found in genes critical for gonadal sex determination and in highly differentiated cell types.
- Poorly differentiated cells, like somatic progenitors, exhibited more divergent transcriptomic profiles between species.
Conclusions:
- Significant transcriptomic divergence exists between human and mouse gonadal development, especially in early progenitor cells.
- The mouse model is suitable for studying specific aspects of human gonadal development and disorders, but limitations exist.
- This comparative atlas will refine the use of animal models in reproductive biology research.
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