Loss of Adgra3 causes obstructive azoospermia with high penetrance in male mice

Maja L. Nybo, Jone M. Kvam, John E. Nielsen, Hanne Frederiksen, Katja Spiess, Kristian H. R. Jensen, Sarina Gadgaard, Anna L. S. Walser, Jesper S. Thomsen, Pamela Cowin, Anders Juul, Martin B. Jensen, Mette M. Rosenkilde*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

2 Citations (Scopus)
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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.

Original languageEnglish
Article number22781
JournalFASEB Journal
Volume37
Issue number2
Number of pages13
ISSN0892-6638
DOIs
Publication statusPublished - 2023

Keywords

  • adhesion G protein-coupled receptor
  • ejaculatory duct
  • ejaculatory duct obstruction
  • estrogen
  • GPR125
  • infertility
  • seminal vesicles
  • Wnt signaling
  • EFFERENT DUCTULES
  • UROGENITAL SINUS
  • MALE-INFERTILITY
  • BETA-CATENIN
  • EXPRESSION
  • ESTROGEN
  • MOUSE
  • EPIDIDYMIS
  • EPITHELIUM
  • RAT

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