Sfrp1 and Sfrp2 are required for normal male sexual development in mice

Area of Science:

• Developmental Biology
• Genetics
• Endocrinology

Background:

• Secreted frizzled-related proteins (Sfrps) are known WNT signaling antagonists involved in various biological processes.
• Their specific roles in mammalian embryonic organogenesis, particularly sexual development, remain largely unexplored.

Purpose of the Study:

• To investigate the role of Sfrp1 and Sfrp2 in mammalian embryonic sexual development.
• To elucidate the function of Sfrps in gonad morphology, reproductive tract maturation, and positioning.

Main Methods:

• In vivo loss-of-function studies using Sfrp1 and Sfrp2 knockout mouse models.
• Analysis of embryonic development at 16.5 days post-coitum (dpc).
• Examination of gonad morphology, reproductive tract, gubernaculum development, and gene expression (Insl3, Lgr8).

Main Results:

• Sfrp1 and Sfrp2 exhibit redundant roles in mouse embryonic sexual development.
• Male embryos lacking both Sfrp1 and Sfrp2 display defects in gonad morphology, reproductive tract maturation, and positioning.
• Abnormal testis positioning is linked to failed gubernaculum development.
• Despite smaller testes and fewer cords, Insl3 and Lgr8 expression persists, suggesting normal ligand/receptor function for testicular descent.

Conclusions:

• Sfrp1 and Sfrp2 are crucial for normal embryonic sexual development in mice.
• Disrupted Sfrp1/Sfrp2 signaling may contribute to reproductive abnormalities through mechanisms potentially involving non-canonical WNT pathways.
• These findings highlight a novel role for Sfrps in the intricate process of mammalian gonad development and positioning.