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Here, we show that the influx of HCO3\u2212, a trigger of capacitation, is impaired and intracellular pH (pHi) is decreased in the sperm of Slc22a14 knockout (KO) mice. While intracellular cAMP concentration did not increase during capacitation in Slc22a14 KO spermatozoa, HCO3\u2212-dependent soluble adenylate cyclase activity was normal, and the addition of 8-bromo cAMP rescued the decreased protein tyrosine phosphorylation. In addition, the pHi of Slc22a14 KO sperm was lower than that of WT sperm and did not increase after the addition of HCO3\u2212. Although its relationship to the regulation of pHi is unknown, transmembrane protein 225, a possible protein phosphatase inhibitor, was found to be decreased in Slc22a14 KO sperm. The decreased in vitro fertilization rate of Slc22a14 KO sperm was partially rescued by an increase in the pHi and the addition of 8-bromo cAMP. These results suggest that SLC22A14 is involved in capacitation through the regulation of HCO3\u2212 transport and pHi.<\/jats:p>","DOI":"10.1530\/rep-21-0135","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T11:05:23Z","timestamp":1635332723000},"page":"23-32","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":3,"title":["Dysregulation of intracellular pH is a cause of impaired capacitation in\n                    <i>Slc22a14<\/i>\n                    -deficient mice"],"prefix":"10.1093","volume":"163","author":[{"given":"Momoe","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Applied Life Sciences , Faculty of Agriculture, Shizuoka University, Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Unou","sequence":"additional","affiliation":[{"name":"Department of Agriculture , Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiya","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Applied Life Sciences , Faculty of Agriculture, Shizuoka University, Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhei","family":"So","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Perinatal Medicine , Hamamatsu University School of Medicine, Shizuoka, Japan"},{"name":"Tawara IVF Clinic , Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Virology and Parasitology , Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichiro","family":"Yogo","sequence":"additional","affiliation":[{"name":"Department of Applied Life 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