Loss of Adgra3 causes obstructive azoospermia with high penetrance in male mice
Abstract
The adhesion receptor ADGRA3 (GPR125) is a known spermatogonial stem cell marker, but its impact on male reproduction and fertility has not been examined. Using a mouse model lacking Adgra3 (Adgra3−/−), we show that 55% of the male mice are infertile from puberty despite having normal spermatogenesis and epididymal sperm count. Instead, male mice lacking Adgra3 exhibited decreased estrogen receptor alpha expression and transient dilation of the epididymis. Combined with an increased estradiol production, this indicates a post‐pubertal hormonal imbalance and fluid retention. Dye injection revealed a blockage between the ejaculatory duct and the urethra, which is rare in mice suffering from infertility, thereby mimicking the etiologies of obstructive azoospermia found in human male infertility. To summarize, male reproductive tract development is dependent on ADGRA3 function that in concert with estrogen signaling may influence fluid handling during sperm maturation and storage.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 23, 2023
- Source ID
- 10.1096/fj.202200762rr
Entities
People
- Anders Juul
- Anna L. S. Walser
- Hanne Frederiksen
- Jesper S. Thomsen
- John E. Nielsen
- Jone M. Kvam
- Katja Spiess
- Kristian H. R. Jensen
- Maja L. Nybo
- Martin Blomberg Jensen
- Mette M. Rosenkilde
- Pamela Cowin
- Sarina Gadgaard
Organizations
- Aarhus University
- Copenhagen University Hospital
- Harvard University
- Lundbeck Foundation
- New York University
- Novo Nordisk Fonden
- United States Department of Defense
- University of Copenhagen