{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:37Z","timestamp":1792789117800,"version":"4.5.0"},"reference-count":206,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Social Development Project of Jiangsu Province","award":["BE2022765"],"award-info":[{"award-number":["BE2022765"]}]},{"name":"Social Development Project of Jiangsu Province","award":["MS22022087"],"award-info":[{"award-number":["MS22022087"]}]},{"name":"Social Development Project of Jiangsu Province","award":["JC22022086"],"award-info":[{"award-number":["JC22022086"]}]},{"name":"Social Development Project of Jiangsu Province","award":["JSSCRC2021543"],"award-info":[{"award-number":["JSSCRC2021543"]}]},{"name":"Nantong Social and People\u2019s Livelihood Science and Technology Plan","award":["BE2022765"],"award-info":[{"award-number":["BE2022765"]}]},{"name":"Nantong Social and People\u2019s Livelihood Science and Technology Plan","award":["MS22022087"],"award-info":[{"award-number":["MS22022087"]}]},{"name":"Nantong Social and People\u2019s Livelihood Science and Technology Plan","award":["JC22022086"],"award-info":[{"award-number":["JC22022086"]}]},{"name":"Nantong Social and People\u2019s Livelihood Science and Technology Plan","award":["JSSCRC2021543"],"award-info":[{"award-number":["JSSCRC2021543"]}]},{"name":"Basic Science Research Program of Nantong","award":["BE2022765"],"award-info":[{"award-number":["BE2022765"]}]},{"name":"Basic Science Research Program of Nantong","award":["MS22022087"],"award-info":[{"award-number":["MS22022087"]}]},{"name":"Basic Science Research Program of Nantong","award":["JC22022086"],"award-info":[{"award-number":["JC22022086"]}]},{"name":"Basic Science Research Program of Nantong","award":["JSSCRC2021543"],"award-info":[{"award-number":["JSSCRC2021543"]}]},{"name":"Jiangsu Innovation and Entrepreneurship Talent Plan","award":["BE2022765"],"award-info":[{"award-number":["BE2022765"]}]},{"name":"Jiangsu Innovation and Entrepreneurship Talent Plan","award":["MS22022087"],"award-info":[{"award-number":["MS22022087"]}]},{"name":"Jiangsu Innovation and Entrepreneurship Talent Plan","award":["JC22022086"],"award-info":[{"award-number":["JC22022086"]}]},{"name":"Jiangsu Innovation and Entrepreneurship Talent Plan","award":["JSSCRC2021543"],"award-info":[{"award-number":["JSSCRC2021543"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>pH homeostasis is crucial for spermatogenesis, sperm maturation, sperm physiological function, and fertilization in mammals. HCO3\u2212 and H+ are the most significant factors involved in regulating pH homeostasis in the male reproductive system. Multiple pH-regulating transporters and ion channels localize in the testis, epididymis, and spermatozoa, such as HCO3\u2212 transporters (solute carrier family 4 and solute carrier family 26 transporters), carbonic anhydrases, and H+-transport channels and enzymes (e.g., Na+-H+ exchangers, monocarboxylate transporters, H+-ATPases, and voltage-gated proton channels). Hormone-mediated signals impose an influence on the production of some HCO3\u2212 or H+ transporters, such as NBCe1, SLC4A2, MCT4, etc. Additionally, ion channels including sperm-specific cationic channels for Ca2+ (CatSper) and K+ (SLO3) are directly or indirectly regulated by pH, exerting specific actions on spermatozoa. The slightly alkaline testicular pH is conducive to spermatogenesis, whereas the epididymis\u2019s low HCO3\u2212 concentration and acidic lumen are favorable for sperm maturation and storage. Spermatozoa pH increases substantially after being fused with seminal fluid to enhance motility. In the female reproductive tract, sperm are subjected to increasing concentrations of HCO3\u2212 in the uterine and fallopian tube, causing a rise in the intracellular pH (pHi) of spermatozoa, leading to hyperpolarization of sperm plasma membranes, capacitation, hyperactivation, acrosome reaction, and ultimately fertilization. The physiological regulation initiated by SLC26A3, SLC26A8, NHA1, sNHE, and CFTR localized in sperm is proven for certain to be involved in male fertility. This review intends to present the key factors and characteristics of pHi regulation in the testes, efferent duct, epididymis, seminal fluid, and female reproductive tract, as well as the associated mechanisms during the sperm journey to fertilization, proposing insights into outstanding subjects and future research trends.<\/jats:p>","DOI":"10.3390\/biom14060685","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T06:47:30Z","timestamp":1718174850000},"page":"685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["pH Homeodynamics and Male Fertility: A Coordinated Regulation of Acid-Based Balance during Sperm Journey to Fertilization"],"prefix":"10.3390","volume":"14","author":[{"given":"Pengyuan","family":"Dai","sequence":"first","affiliation":[{"name":"Institute of Reproductive Medicine, Medical School, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Medicine, Medical School, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Medicine, Medical School, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Medicine, Medical School, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-866X","authenticated-orcid":false,"given":"Xiaoning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Medicine, Medical School, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Medicine, Medical School, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16.e1","DOI":"10.1016\/j.fertnstert.2008.09.046","article-title":"A public health focus on infertility prevention, detection, and management","volume":"93","author":"Macaluso","year":"2010","journal-title":"Fertil. 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