SLC9A3 Affects Vas Deferens Development and Associates with Taiwanese Congenital Bilateral Absence of the Vas Deferens.
Journal
BioMed research international
ISSN: 2314-6141
Titre abrégé: Biomed Res Int
Pays: United States
ID NLM: 101600173
Informations de publication
Date de publication:
2019
2019
Historique:
received:
29
10
2018
revised:
06
01
2019
accepted:
03
02
2019
entrez:
9
4
2019
pubmed:
9
4
2019
medline:
23
7
2019
Statut:
epublish
Résumé
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. The objective of the study was to test whether SLC9A3 variants cause Taiwanese CBAVD. Six-month-old 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. 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 The data implicate loss of SLC9A3 as a basis of Taiwanese CBAVD and highlight SLC9A3 function in reproduction.
Sections du résumé
BACKGROUND
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
OBJECTIVE
The objective of the study was to test whether SLC9A3 variants cause Taiwanese CBAVD.
MATERIALS AND METHODS
METHODS
Six-month-old
RESULTS
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
CONCLUSIONS
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
CONCLUSION
CONCLUSIONS
The data implicate loss of SLC9A3 as a basis of Taiwanese CBAVD and highlight SLC9A3 function in reproduction.
Identifiants
pubmed: 30956978
doi: 10.1155/2019/3562719
pmc: PMC6431446
doi:
Substances chimiques
SLC9A3 protein, human
0
Slc9a3 protein, mouse
0
Sodium-Hydrogen Exchanger 3
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3562719Références
Am J Physiol Renal Physiol. 2001 Mar;280(3):F426-36
pubmed: 11181404
J Biol Chem. 2001 May 18;276(20):17236-43
pubmed: 11278980
Hum Reprod. 2001 Oct;16(10):2093-7
pubmed: 11574497
Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14132-7
pubmed: 11698654
J Androl. 2002 Mar-Apr;23(2):237-41
pubmed: 11868817
Hum Reprod. 2002 Aug;17(8):2066-72
pubmed: 12151438
MLO Med Lab Obs. 2002 Oct;34(10):8-12; quiz 14, 16
pubmed: 12385171
J Biol Chem. 2002 Dec 27;277(52):50503-9
pubmed: 12403779
Am J Med Genet A. 2003 Jul 15;120A(2):296-8
pubmed: 12833420
Hum Reprod. 2004 Feb;19(2):250-3
pubmed: 14747162
Hum Reprod. 2004 May;19(5):1094-100
pubmed: 15070876
J Biol Chem. 1992 May 5;267(13):9331-9
pubmed: 1577762
Hum Reprod. 2005 Sep;20(9):2470-5
pubmed: 15905293
Mol Hum Reprod. 2006 Feb;12(2):107-11
pubmed: 16421216
Reproduction. 2007 Apr;133(4):775-84
pubmed: 17504921
Hum Reprod. 2009 Mar;24(3):748-55
pubmed: 19095672
Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G886-98
pubmed: 19164484
Clin Genet. 2009 Sep;76(3):282-6
pubmed: 19737283
Urology. 2013 Aug;82(2):345-51
pubmed: 23768522
Science. 1989 Sep 8;245(4922):1066-73
pubmed: 2475911
J Urol. 1989 Jul;142(1):62-5
pubmed: 2499695
PLoS Genet. 2017 Apr 6;13(4):e1006715
pubmed: 28384194
Gene. 2017 Sep 20;629:117-126
pubmed: 28756021
J Urol. 1971 Oct;106(4):568-74
pubmed: 4399160
J Clin Invest. 1994 Jan;93(1):106-13
pubmed: 8282777
Am J Physiol. 1996 Jan;270(1 Pt 1):G29-41
pubmed: 8772498
Nat Genet. 1998 Jul;19(3):282-5
pubmed: 9662405
J Med Genet. 1998 Jul;35(7):594-6
pubmed: 9678705