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Whole Ovary Immunofluorescence, Clearing, and Multiphoton Microscopy for Quantitative 3D Analysis of the Developing Ovarian Reserve in Mouse
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Somatic FGFR2 is Required for Germ Cell Maintenance in the Mouse Ovary
Anthony D Bird1,2, Emily R Frost2,3, Stefan Bagheri-Fam2,3
1Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, 3010, Australia.
Endocrinology
|February 14, 2023
Summary
Fibroblast growth factor receptor 2c (FGFR2c) is crucial for maintaining ovarian germ cells, acting antagonistically with FOXL2. FGFR2 is not essential for testis development after sex determination.
Area of Science:
- Developmental Biology
- Reproductive Biology
- Genetics
Background:
- Fibroblast growth factor 9 (FGF9) signaling through fibroblast growth factor receptor 2c (FGFR2c) is vital for male sex determination and testis development in mice.
- The roles of FGFR2 in ovarian development and its necessity in testes post-sex determination remain unclear.
- FGFR2 exhibits sexually dimorphic expression in fetal mouse gonads.
Purpose of the Study:
- To investigate the function of FGFR2 in the developing mouse ovary.
- To determine if FGFR2 is required for testis maintenance after sex determination.
- To elucidate the interaction between FGFR2 and FOXL2 in germ cell development.
Main Methods:
- Generation of Fgfr2c knockout mice (XX and XY).
- Analysis of gonadal development and germ cell populations using genetic deletion models.
- Examination of FGFR2 expression patterns in fetal gonads.
Main Results:
- Deletion of Fgfr2c in female mice (XX) resulted in a significant loss of ovarian germ cells, indicating FGFR2c's essential role in germ cell maintenance.
- Ablation of Foxl2 rescued the germ cell loss in Fgfr2c knockout mice, revealing an antagonistic relationship between FGFR2 and FOXL2.
- Male mice (XY) with Fgfr2 deletion showed normal testis development and structure, demonstrating FGFR2 is not critical for Sertoli cell fate post-sex determination.
Conclusions:
- FGFR2c is indispensable for the survival of germ cells within the developing ovary.
- FGFR2 and FOXL2 pathways interact antagonistically to regulate germ cell development.
- FGFR2 is not required for maintaining Sertoli cell function or testis morphology after the initial sex determination phase.
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