Loss of SLC9A3 decrease CFTR protein and causes obstructed azoospermia in mice

by Ya-Yun Wang, Ying-Hung Lin, Yi-No Wu, Yen-Lin Chen, Yung-Chih Lin, Chiao-Yin Cheng, Han-Sun Chiang Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF) and are associated with congenital bilateral absence of the vas deferens (CBAVD), which is the major cause of infertility in male patients with CF. However, most Taiwanese patients with CBAVD do not carry majorCFTR mutations. Some patients have a single copy deletion of the solute carrier family 9 isoform 3 (SLC9A3) gene. SLC9A3 is a Na+/H+ exchanger, and depletedSlc9a3 in male mice causes infertility due to the abnormal dilated lumen of the rete testis and efferent ductules. Furthermore, SLC9A3 interacts with CFTR in the pancreatic duct and functions as a genetic modifier of CF. However, SLC9A3 function and its relation to CFTR expression in the male reproductive tract in vivo remain elusive. In the present study, we found that CFTR expression was dramatically decreased in the epididymis and vas deferens ofSlc9a3 knockout mice. AdultSlc9a3-/- mice showed not only significantly decreased epididymis and vas deferens weight but also increased testis weight. Furthermore,Slc9a3-/- mice developed obstructive azoospermia because of abnormal abundant secretions and calcification in the lumen of the reproductive tract. Ultrastructural analysis of the epithelium inSlc9a3–/–epididymis and vas deferens displayed disorganized and reduced number of stereocilia and numerous secr...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research