Abstract
Background The pathophysiology of Taiwanese congenital bilateral absence of the vas deferens (CBAVD) is different from that in Caucasians. In particular, major cystic fibrosis transmembrane conductance regulator (CFTR) mutations and cystic fibrosis are absent in the former. Instead, deficiency in solute carrier family 9 sodium/hydrogen exchanger isoform 3 (SLC9A3) may play a role by generating obstructive azoospermia and degraded epithelial structure in the reproductive tract. Objectives The objective of the study was to test whether SLC9A3 variants cause Taiwanese CBAVD. Materials and Methods Six-month-old Slc9a3−/−male mice were used to evaluate the effect of long-term SLC9A3 loss on the reproductive system. A case-control cohort of 29 men with CBAVD and 32 fertile men were genotyped for SLC9A3 variants. Results SLC9A3 was expressed and localized in the apical border of the epithelium of human vas deferens and glandular epithelium of the seminal vesicle. SLC9A3 deficiency specifically induces atrophy of vas deferens and unfolding of seminal vesicle mucosa in mice. Loss of SLC9A3 increased the incidence of CBAVD in humans from 3.1% to 37.9% (p < 0.001). Up to 75.9% of CBAVD patients carry at least one variant in either SLC9A3 or CFTR. Discussion Our findings build upon previous data associated with CBAVD pathogenesis. Here, we now report for the first time an association between CBAVD and loss of SLC9A3 and propose that specific defects in the reproductive duct due to SLC9A3 variants drive CBAVD development. Conclusion The data implicate loss of SLC9A3 as a basis of Taiwanese CBAVD and highlight SLC9A3 function in reproduction.
Highlights
Congenital bilateral absence of the vas deferens (CBAVD) accounts for 1% to 2% of cases of male infertility [1] and is the most frequent cause of obstructive azoospermia [2]
Because SLC9A3 is abundantly expressed in mouse reproductive organs [19], we tested whether long-term loss of SLC9A3 impairs development of the vas deferens
The weight of the seminal vesicle was significantly lower (Table 1). These changes were absent in young Slc a −/− mice. These data suggested that Slc a −/− mice exhibited features similar to those in men with congenital bilateral absence of the vas deferens (CBAVD), as observed by magnetic resonance imaging (MRI) [20]
Summary
Congenital bilateral absence of the vas deferens (CBAVD) accounts for 1% to 2% of cases of male infertility [1] and is the most frequent cause of obstructive azoospermia [2]. CFTR variants have been identified in 50% to 74% of alleles in CBAVD patients [5,6,7]. The CFTR-mutation spectrum among 63 infertile Taiwanese men with CBAVD is narrow, with a polythymidine (Tn) variant in intron 8 (IVS8-5T) accounting for 91.3% (42/46) of the variants observed, most of the identified variants (27/63, 42.9%) were indeterminate [9]. The objective of the study was to test whether SLC9A3 variants cause Taiwanese CBAVD. Up to 75.9% of CBAVD patients carry at least one variant in either SLC9A3 or CFTR. The data implicate loss of SLC9A3 as a basis of Taiwanese CBAVD and highlight SLC9A3 function in reproduction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
