{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T06:30:30Z","timestamp":1766557830764,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Microfluidic platforms have emerged as critical technologies for exploring sperm chemotaxis, providing precise gradient control, and facilitating in-depth behavioral assessment. We designed a novel, user-friendly microfluidic device that is optimized for human sperm morphology and motility. The device was validated using two well-established sperm chemoattractants, progesterone and bourgeonal, demonstrating its reliability and reproducibility. Given the key role of olfactory receptors (ORs) in mediating sperm chemotaxis, the newly developed device was employed to identify additional receptors that may contribute to sperm behavior. Using the Atlas database, we identified OR2H1 as a candidate receptor. It is enriched in testis-derived cells, particularly in early and late spermatids, and it is broadly expressed across human spermatozoa. We demonstrated that OR2H1\u2019s ligand, methional, a sulfur-containing aldehyde naturally found in vaginal fluid and biosynthesized by Lactococcus lactis, significantly enhances sperm migration and progressive motility. Methional stimulation also triggered increased intracellular calcium levels, indicating receptor activation. Computer-assisted sperm analysis revealed that methional treatment improved sperm linearity, straightness, and wobble without affecting the average velocity, suggesting enhanced directional movement. These findings provide evidence that methional promotes sperm chemotaxis via OR2H1 and highlight the potential role of the vaginal microbiome in influencing human fertility.<\/jats:p>","DOI":"10.3390\/cells14130944","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T08:13:56Z","timestamp":1750407236000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring OR2H1-Mediated Sperm Chemotaxis: Development and Application of a Novel Microfluidic Device"],"prefix":"10.3390","volume":"14","author":[{"given":"Fiorella","family":"Di Nicuolo","sequence":"first","affiliation":[{"name":"International Scientific Institute Paul VI, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Teveroni","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8104-5195","authenticated-orcid":false,"given":"Alessandro","family":"Devigili","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35122 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9172-1142","authenticated-orcid":false,"given":"Clelia","family":"Gasparini","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35122 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of Sacred Heart, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tullio","family":"Ghi","sequence":"additional","affiliation":[{"name":"International Scientific Institute Paul VI, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Life Sciences and Public Health, Catholic University of Sacred Heart Rome Campus, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Internal Medicine, Endocrinology and Diabetology, Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Milardi","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Internal Medicine, Endocrinology and Diabetology, Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Mancini","sequence":"additional","affiliation":[{"name":"International Scientific Institute Paul VI, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1021\/ac052087i","article-title":"Chemotaxis Assays of Mouse Sperm on Microfluidic Devices","volume":"78","author":"Koyama","year":"2006","journal-title":"Anal. 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