{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:01:35Z","timestamp":1790622095508,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T00:00:00Z","timestamp":1752364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD069631"],"award-info":[{"award-number":["R01 HD069631"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>What effect do toxins produced by bacterial vaginosis (BV) bacteria have on sperm function?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>BV toxins dysregulate sperm capacitation and intracellular calcium homeostasis, and impair the ability of sperm to fertilize oocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>In BV, which is linked to infertility, overgrowth of Prevotella and Gardnerella in the vagina is accompanied by elevated concentrations of the toxins lipopolysaccharide (LPS) and vaginolysin (VLY).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This was a laboratory study in which human semen samples were collected from consenting healthy donors with normal semen parameters. Mouse sperm samples were obtained from the caudal epididymis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>Motile mouse and human sperm were isolated via swim-up and treated under non-capacitating or capacitating conditions. LPS from Escherichia coli was commercially available. VLY was produced by cloning the Gardnerella VLY protein in the ClearColi expression system. Mouse sperm were pre-incubated in IVF medium with LPS or VLY and then co-cultured with ovulated cumulus\u2013oocyte complexes. The effects of LPS and VLY on sperm motility and hyperactivation were assessed with computer-assisted sperm analysis. Effects on viability were assessed by Hoechst staining. Acrosomal exocytosis was assessed in sperm from transgenic Acr-eGFP mice and in human sperm stained with Pisum sativum agglutinin FITC. Intracellular calcium concentration was measured by using the calcium-sensitive dye Fluo-4 AM and fluorescence microscopy. The effects of LPS on sperm from CatSper knockout mice were assessed. Additionally, sperm were treated with a Toll-like receptor 4 (TLR4) antagonist and further exposed to LPS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>Exposure of mouse sperm to LPS or VLY significantly decreased IVF (P\u2009&amp;lt;\u20090.05). Under capacitating conditions, both toxins initially increased mouse (P\u2009&amp;lt;\u20090.001) and human (P\u2009&amp;lt;\u20090.05) sperm hyperactivation, then significantly decreased sperm motility (P\u2009&amp;lt;\u20090.05), hyperactivation (P\u2009&amp;lt;\u20090.05), and acrosomal exocytosis (P\u2009&amp;lt;\u20090.01). These changes were accompanied by a rapid and irreversible increase in sperm intracellular calcium concentration. Effects of LPS, but not VLY, were prevented by polymyxin B, which binds LPS. The LPS-induced intracellular calcium increase required external calcium, but not the calcium channel CatSper, and was inhibited by a TLR4 antagonist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LARGE SCALE DATA<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>First, the commercially available LPS we used was isolated from Escherichia coli, rather than from the BV-associated bacteria Prevotella bivia. Second, we did not quantify the absolute sperm intracellular calcium concentration before or after LPS or VLY treatment. Third, all of our experiments were in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>These studies suggest that BV-associated toxins contribute to infertility, in part, by impairing sperm capacitation and reducing their fertilizing ability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>This work was supported by the National Institutes of Health (grant number R01 HD069631 to C.M.S.). The authors declare that they have no conflict of interest.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deaf132","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T07:51:16Z","timestamp":1750924276000},"page":"1720-1734","source":"Crossref","is-referenced-by-count":10,"title":["Bacterial vaginosis toxins impair sperm capacitation and fertilization"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-3264","authenticated-orcid":false,"given":"Shweta","family":"Bhagwat","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine , Saint Louis, MO,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Asadi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine , Saint Louis, 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