A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR
| Autor: | Kristiina Aittomäki, Liana Shimshilashvili, Jorma Toppari, Juha S. Tapanainen, Satu Wedenoja, Pia Höglund, Outi Hovatta, Ahlam Khamaysi, Juha Kere, Outi Elomaa, Ehud Ohana, Shireen Anbtawe-Jomaa, Christer Holmberg |
|---|---|
| Přispěvatelé: | Clinicum, Department of Obstetrics and Gynecology, University of Helsinki, Research Programs Unit, Research Programme for Molecular Neurology, Genome-Scale Biology (GSB) Research Program, Kristiina Aittomäki / Principal Investigator, Department of Medical and Clinical Genetics, Medicum, HUSLAB, Children's Hospital, Lastentautien yksikkö, Reproductive Disease Modeling, Juha Kere / Principal Investigator, HUS Gynecology and Obstetrics, HUS Children and Adolescents |
| Rok vydání: | 2017 |
| Předmět: |
Male
Models Molecular 0301 basic medicine Protein Conformation lcsh:Medicine Cystic Fibrosis Transmembrane Conductance Regulator VAS-DEFERENS Cystic fibrosis Male infertility 0302 clinical medicine Missense mutation Chloride-Bicarbonate Antiporters lcsh:Science CYSTIC-FIBROSIS GENE 030219 obstetrics & reproductive medicine Multidisciplinary Molecular medicine biology Cystic fibrosis transmembrane conductance regulator TRANSMEMBRANE CONDUCTANCE REGULATOR Sulfate Transporters DEPENDENT HCO3-TRANSPORT SPERM FERTILIZING-CAPACITY Infertility Heterozygote medicine.medical_specialty Congenital chloride diarrhea Mutation Missense CONGENITAL CHLORIDE DIARRHEA SLC26A3 Article Andrology 03 medical and health sciences Internal medicine medicine Humans Amino Acid Sequence Infertility Male MALE-INFERTILITY lcsh:R Heterozygote advantage medicine.disease MOLECULAR-MECHANISM 030104 developmental biology Endocrinology EXCHANGER DRA biology.protein lcsh:Q 3111 Biomedicine REPRODUCTIVE-TRACT |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-14606-3 |
| Popis: | Chloride absorption and bicarbonate excretion through exchange by the solute carrier family 26 member 3 (SLC26A3) and cystic fibrosis transmembrane conductance regulator (CFTR) are crucial for many tissues including sperm and epithelia of the male reproductive tract. Homozygous SLC26A3 mutations cause congenital chloride diarrhea with male subfertility, while homozygous CFTR mutations cause cystic fibrosis with male infertility. Some homozygous or heterozygous CFTR mutations only manifest as male infertility. Accordingly, we studied the influence of SLC26A3 on idiopathic infertility by sequencing exons of SLC26A3 in 283 infertile and 211 control men. A heterozygous mutation c.2062 G > C (p.Asp688His) appeared in nine (3.2%) infertile men, and additionally, in two (0.9%) control men, whose samples revealed a sperm motility defect. The p.Asp688His mutation is localized in the CFTR-interacting STAS domain of SLC26A3 and enriched in Finland, showing a significant association with male infertility in comparison with 6,572 Finnish (P P −/HCO3− exchange activity but suppresses CFTR, despite unaffected domain binding and expression. These results suggest a novel mechanism for human male infertility─impaired anion transport by the coupled SLC26A3 and CFTR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|