Loss of Adgra3 causes obstructive azoospermia with high penetrance in male mice
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Loss of Adgra3 causes obstructive azoospermia with high penetrance in male mice. / Nybo, Maja L.; Kvam, Jone M.; Nielsen, John E.; Frederiksen, Hanne; Spiess, Katja; Jensen, Kristian H. R.; Gadgaard, Sarina; Walser, Anna L. S.; Thomsen, Jesper S.; Cowin, Pamela; Juul, Anders; Jensen, Martin B.; Rosenkilde, Mette M.
In: FASEB Journal, Vol. 37, No. 2, 22781, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Loss of Adgra3 causes obstructive azoospermia with high penetrance in male mice
AU - Nybo, Maja L.
AU - Kvam, Jone M.
AU - Nielsen, John E.
AU - Frederiksen, Hanne
AU - Spiess, Katja
AU - Jensen, Kristian H. R.
AU - Gadgaard, Sarina
AU - Walser, Anna L. S.
AU - Thomsen, Jesper S.
AU - Cowin, Pamela
AU - Juul, Anders
AU - Jensen, Martin B.
AU - Rosenkilde, Mette M.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - adhesion G protein-coupled receptor
KW - ejaculatory duct
KW - ejaculatory duct obstruction
KW - estrogen
KW - GPR125
KW - infertility
KW - seminal vesicles
KW - Wnt signaling
KW - EFFERENT DUCTULES
KW - UROGENITAL SINUS
KW - MALE-INFERTILITY
KW - BETA-CATENIN
KW - EXPRESSION
KW - ESTROGEN
KW - MOUSE
KW - EPIDIDYMIS
KW - EPITHELIUM
KW - RAT
U2 - 10.1096/fj.202200762RR
DO - 10.1096/fj.202200762RR
M3 - Journal article
C2 - 36688818
VL - 37
JO - F A S E B Journal
JF - F A S E B Journal
SN - 0892-6638
IS - 2
M1 - 22781
ER -
ID: 335688773