Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848676 (male subfertility)
 265 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital chloride diarrhoea (CLD) is a rare inherited disease caused by mutations in the solute carrier family 26 member 3 (SLC26A3) gene. Disruption of intestinal Cl(-)/HCO(3)(-) exchange causes watery Cl(-) rich diarrhoea from birth, and recently male subfertility was observed as a novel manifestation. Expression of SLC26A3, together with interacting proteins cystic fibrosis transmembrane conductance regulator (CFTR) and Na(+)/H(+) exchanger 3 (NHE3), was studied using immunohistochemistry in the testis (n = 2) and efferent ducts (ED) (n = 1) of patients with CLD (V317del genotype) and in the testis and epididymis (n = 11), seminal vesicle (n = 9) and prostate (n = 4) of the controls. SLC26A3 was immunolocalized in the head of the elongating spermatids (stages III-VI) and CFTR in the elongating spermatids (stages III and IV) and pachytene (stages III-V) and diplotene spermatocytes. In the non-ciliated cells of the ED, apical expression of all three proteins was observed, but only SLC26A3 and CFTR were detected on the luminal border of the apical mitochondria-rich cells (AMRC) of the ductus epididymis and in the epithelium of the seminal vesicle. Only CFTR was present in the epithelium of the prostatic duct. In the patient with CLD, the expression of both SLC26A3 and CFTR was absent in the ED, but testicular expression was identical to that of the controls. These results suggest a primary role for SLC26A3 in male reproduction. Tissue-specific co-expression with CFTR and NHE3 supports diverse functions of SLC26A3 and may have an impact on pathophysiology of male subfertility both in CLD and in cystic fibrosis (CF), as well as spermatoceles.
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PMID:Expression of SLC26A3, CFTR and NHE3 in the human male reproductive tract: role in male subfertility caused by congenital chloride diarrhoea. 1642 Dec 16

Congenital chloride diarrhoea (CLD, OMIM214700) is a rare genetic disease caused by mutations in a plasma membrane protein, the solute-linked carrier family 26 member A3 (SLC26A3) protein, which encodes for an epithelial anion exchanger for Cl- and HCO3-. The main clinical symptom is a lifetime watery diarrhoea with a high Cl- content and low pH, causing dehydration and hypochloremic metabolic alkalosis. CLD may be fatal, if not adequately treated by substitution of NaCl, KCl and fluid lost in the faeces. Long-term prognosis is generally favourable, but complications such as renal disease, inflammatory bowel disease, hyperuricemia, inguinal hernias, spermatoceles and male subfertility are possible. The role of dysfunctional SLC26A3 in the pathogenesis of these complications is poorly known. Altogether 30 different mutations of the SLC26A3 gene are currently known among patients with CLD; the most common of them being the three founder mutations present among Finns (V317del), Polish (I675676ins) and Arabic (G187X) populations. Individual variation in the clinical picture of CLD is common, but not known to associate with the genotype.
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PMID:SLC26A3 and congenital chloride diarrhoea. 1712 Jul 62

Members of the solute carrier 26 (SLC26) family have emerged as important players in mediating anions fluxes across the plasma membrane of epithelial cells, in cooperation with the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Among them, SLC26A3 acts as a chloride/bicarbonate exchanger, highly expressed in the gastrointestinal, pancreatic and renal tissues. In humans, mutations in the SLC26A3 gene were shown to induce congenital chloride-losing diarrhea (CLD), a rare autosomal recessive disorder characterized by life-long secretory diarrhea. In view of some reports indicating subfertility in some male CLD patients together with SLC26-A3 and -A6 expression in the male genital tract and sperm cells, we analyzed the male reproductive parameters and functions of SLC26A3 deficient mice, which were previously reported to display CLD gastro-intestinal features. We show that in contrast to Slc26a6, deletion of Slc26a3 is associated with severe lesions and abnormal cytoarchitecture of the epididymis, together with sperm quantitative, morphological and functional defects, which altogether compromised male fertility. Overall, our work provides new insight into the pathophysiological mechanisms that may alter the reproductive functions and lead to male subfertility in CLD patients, with a phenotype reminiscent of that induced by CFTR deficiency in the male genital tract.
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PMID:Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm fertilization potential in the mouse. 3011 83