{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T21:06:57Z","timestamp":1761599217272,"version":"3.37.3"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI119012"],"award-info":[{"award-number":["R01-AI119012"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The outer layers of the vaginal epithelium (VE) are important because they accumulate glycogen which, under optimal conditions, <jats:italic>Lactobacillus<\/jats:italic> spp. consume to grow and acidify the vaginal microenvironment with lactic acid. We hypothesized that exposure to lubricant, for example in the conduct of a transvaginal ultrasound (TVUS), may contribute to the shedding of mature epithelial cells, exposing immature cells. Cervicovaginal fluid (CVF) was sampled at four time points by menstrual cup (Softdisc\u2122) from 50 women referred for TVUS, during which a controlled volume of lubricant was applied to the TVUS wand. Samples were collected (1) immediately before TVUS and (2) 6\u201312 hours, (3) within one week, and (4) two weeks after TVUS. Clinical vaginal lubricants are similar to commercial lubricants, and often have a high osmolality or pH, and contain bactericides such as methylparaben and propylparaben. The number and maturity of epithelial cells in each CVF sample were measured by quantitative and differential fluorimetry (maturity index, MI). Comparisons of cell-counts and maturity were made by paired Wilcoxon signed-rank tests. Among women with a high pre-TVUS MI (&gt; 3), there was a decrease in median cell-count and mean MI in the sample collected 6\u201312 hours after TVUS (<jats:italic>p<\/jats:italic>&lt;0.001, <jats:italic>n<\/jats:italic> = 26 and <jats:italic>p<\/jats:italic> &lt; 0.001, <jats:italic>n<\/jats:italic> = 26, respectively). For these women, cell-count and MI remained lower in the sample collected within the subsequent week (<jats:italic>p<\/jats:italic>&lt;0.001, <jats:italic>n<\/jats:italic> = 29 and <jats:italic>p&lt;<\/jats:italic>0.01, <jats:italic>n<\/jats:italic> = 29, respectively), and MI remained lower in the sample collected within two weeks of TVUS (<jats:italic>p<\/jats:italic>&lt;0.01, <jats:italic>n<\/jats:italic> = 25), compared to the pre-TVUS sample. Among participants with a low pre-TVUS MI (&lt; 3), cell-count was higher in the sample collected within two weeks of TVUS compared to the pre-TVUS sample (<jats:italic>p<\/jats:italic> = 0.03, <jats:italic>n<\/jats:italic> = 15), but no significant changes in MI were observed. Results were similar when restricted to reproductive-age women. This preliminary data indicates hypertonic vaginal lubricants may increase vaginal epithelial cell shedding.<\/jats:p>","DOI":"10.1371\/journal.pone.0250153","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T17:26:35Z","timestamp":1620062795000},"page":"e0250153","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Observational cohort study of the effect of a single lubricant exposure during transvaginal ultrasound on cell-shedding from the vaginal epithelium"],"prefix":"10.1371","volume":"16","author":[{"given":"D. Elizabeth","family":"O\u2019Hanlon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8354-0077","authenticated-orcid":true,"given":"Sarah E.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina A.","family":"Stennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah J.","family":"Robbins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth D.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelia M.","family":"Wnorowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"Mark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Ravel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Cone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca M.","family":"Brotman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"issue":"2","key":"pone.0250153.ref001","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jri.2011.01.005","article-title":"Innate and adaptive immunity at mucosal surfaces of the female reproductive tract: stratification and integration of immune protection against the transmission of sexually transmitted infections","volume":"88","author":"DK Hickey","year":"2011","journal-title":"J Reprod Immunol"},{"issue":"1","key":"pone.0250153.ref002","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/1040841X.2017.1306688","article-title":"Defence factors of vaginal lactobacilli","volume":"44","author":"S Kovachev","year":"2018","journal-title":"Crit Rev Microbiol"},{"issue":"5","key":"pone.0250153.ref003","doi-asserted-by":"crossref","first-page":"e01084","DOI":"10.1128\/mBio.01084-15","article-title":"Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota","volume":"6","author":"K Nunn","year":"2015","journal-title":"MBio"},{"issue":"4","key":"pone.0250153.ref004","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1067\/mob.2000.108857","article-title":"Epithelial cell layer thickness and immune cell populations in the normal human vagina at different stages of the menstrual cycle","volume":"183","author":"D Patton","year":"2000","journal-title":"Am J Obstet Gynecol"},{"issue":"2","key":"pone.0250153.ref005","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.1471-0528.1934.tb08759.x","article-title":"The Biology of the Vagina in the Human Subject","volume":"41","author":"R Cruickshank","year":"1934","journal-title":"BJOG: An International Journal of Obstetrics & Gynaecology"},{"issue":"7","key":"pone.0250153.ref006","doi-asserted-by":"crossref","first-page":"e102467","DOI":"10.1371\/journal.pone.0102467","article-title":"Free glycogen in vaginal fluids is associated with Lactobacillus colonization and low vaginal pH","volume":"9","author":"P Mirmonsef","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"pone.0250153.ref007","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40168-019-0667-9","article-title":"Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: implications for in vivo dominance of the vaginal microbiota","volume":"7","author":"C van der Veer","year":"2019","journal-title":"Microbiome"},{"key":"pone.0250153.ref008","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/1471-2334-11-200","article-title":"In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide","volume":"11","author":"DE O\u2019Hanlon","year":"2011","journal-title":"BMC Infect Dis"},{"issue":"9","key":"pone.0250153.ref009","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.resmic.2017.04.001","article-title":"The role of lactic acid production by probiotic Lactobacillus species in vaginal health","volume":"168","author":"G Tachedjian","year":"2017","journal-title":"Research in Microbiology"},{"issue":"11","key":"pone.0250153.ref010","doi-asserted-by":"crossref","first-page":"e80074","DOI":"10.1371\/journal.pone.0080074","article-title":"Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota","volume":"8","author":"DE O\u2019Hanlon","year":"2013","journal-title":"PLoS One"},{"issue":"4","key":"pone.0250153.ref011","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00055-18","article-title":"Anti-HIV-1 Activity of Lactic Acid in Human Cervicovaginal Fluid","volume":"3","author":"D Tyssen","year":"2018","journal-title":"mSphere"},{"key":"pone.0250153.ref012","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3389\/fphys.2015.00164","article-title":"Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis","volume":"6","author":"M Aldunate","year":"2015","journal-title":"Front Physiol"},{"key":"pone.0250153.ref013","doi-asserted-by":"crossref","first-page":"446","DOI":"10.3389\/fcimb.2019.00446","article-title":"Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota","volume":"9","author":"DJ Delgado-Diaz","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"issue":"6","key":"pone.0250153.ref014","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/aji.12230","article-title":"The structure of the human vaginal stratum corneum and its role in immune defense","volume":"71","author":"DJ Anderson","year":"2014","journal-title":"Am J Reprod Immunol"},{"key":"pone.0250153.ref015","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fcimb.2020.00106","article-title":"Asymptomatic Bacterial Vaginosis Is Associated With Depletion of Mature Superficial Cells Shed From the Vaginal Epithelium","volume":"10","author":"DE O\u2019Hanlon","year":"2020","journal-title":"Frontiers in cellular and infection microbiology"},{"issue":"1","key":"pone.0250153.ref016","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.qai.0000159671.25950.74","article-title":"In vitro and in vivo: the story of nonoxynol 9","volume":"39","author":"SL Hillier","year":"2005","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"1","key":"pone.0250153.ref017","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1743-6109.2010.02067.x","article-title":"Association of lubricant use with women\u2019s sexual pleasure, sexual satisfaction, and genital symptoms: a prospective daily diary study","volume":"8","author":"D Herbenick","year":"2011","journal-title":"J Sex Med"},{"issue":"2","key":"pone.0250153.ref018","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/jsm.12022","article-title":"Women\u2019s perceptions about lubricant use and vaginal wetness during sexual activities","volume":"10","author":"KN Jozkowski","year":"2013","journal-title":"J Sex Med"},{"issue":"3","key":"pone.0250153.ref019","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3200\/JACH.54.3.143-148","article-title":"Condom discomfort and associated problems with their use among university students","volume":"54","author":"R Crosby","year":"2005","journal-title":"J Am Coll Health"},{"issue":"7","key":"pone.0250153.ref020","first-page":"350","article-title":"Lubrication use in condom promotion among commercial sex workers and their clients in Ratchaburi, Thailand","volume":"78","author":"W Rojanapithayakorn","year":"1995","journal-title":"J Med Assoc Thai"},{"issue":"2","key":"pone.0250153.ref021","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/AOG.0b013e3182426275","article-title":"Effect of lubricating gel on patient comfort during vaginal speculum examination: a randomized controlled trial","volume":"119","author":"D Hill","year":"2012","journal-title":"Obstet Gynecol"},{"issue":"4","key":"pone.0250153.ref022","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s00404-013-3047-x","article-title":"The role of gel application in decreasing pain during speculum examination and its effects on papanicolaou smear results","volume":"289","author":"S Simavli","year":"2014","journal-title":"Arch Gynecol Obstet"},{"issue":"10","key":"pone.0250153.ref023","first-page":"3090","article-title":"Diagnosis and treatment of atrophic vaginitis","volume":"61","author":"G Bachmann","year":"2000","journal-title":"Am Fam Physician"},{"issue":"1","key":"pone.0250153.ref024","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1097\/gme.0b013e31821f92df","article-title":"Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women: an up-to-date review","volume":"19","author":"O Tan","year":"2012","journal-title":"Menopause"},{"issue":"9","key":"pone.0250153.ref025","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1089\/aid.2010.0252","article-title":"Identification of personal lubricants that can cause rectal epithelial cell damage and enhance HIV type 1 replication in vitro","volume":"27","author":"O Begay","year":"2011","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"3","key":"pone.0250153.ref026","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3390\/pharmaceutics6030530","article-title":"Characterization of commercially available vaginal lubricants: a safety perspective","volume":"6","author":"A Cunha","year":"2014","journal-title":"Pharmaceutics"},{"issue":"12","key":"pone.0250153.ref027","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1093\/infdis\/jiz412","article-title":"Personal and Clinical Vaginal Lubricants: Impact on Local Vaginal Microenvironment and Implications for Epithelial Cell Host Response and Barrier Function","volume":"220","author":"EM Wilkinson","year":"2019","journal-title":"J Infect Dis"},{"issue":"5","key":"pone.0250153.ref028","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.tiv.2005.10.002","article-title":"Organotypic human vaginal-ectocervical tissue model for irritation studies of spermicides, microbicides, and feminine-care products","volume":"20","author":"S Ayehunie","year":"2006","journal-title":"Toxicol In Vitro"},{"key":"pone.0250153.ref029","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.toxrep.2017.12.011","article-title":"Hyperosmolal vaginal lubricants markedly reduce epithelial barrier properties in a three-dimensional vaginal epithelium model","volume":"5","author":"S Ayehunie","year":"2018","journal-title":"Toxicol Rep"},{"issue":"6","key":"pone.0250153.ref030","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/00007435-200406000-00005","article-title":"Relative safety of sexual lubricants for rectal intercourse","volume":"31","author":"K Sudol","year":"2004","journal-title":"Sex Transm Dis"},{"issue":"5","key":"pone.0250153.ref031","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/OLQ.0b013e3181644669","article-title":"Mucosal irritation potential of personal lubricants relates to product osmolality as detected by the slug mucosal irritation assay","volume":"35","author":"E Adriaens","year":"2008","journal-title":"Sex Transm Dis"},{"issue":"5","key":"pone.0250153.ref032","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1086\/511279","article-title":"Hyperosmolar sexual lubricant causes epithelial damage in the distal colon: potential implication for HIV transmission","volume":"195","author":"E Fuchs","year":"2007","journal-title":"J Infect Dis"},{"issue":"3","key":"pone.0250153.ref033","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1089\/aid.2018.0304","article-title":"The Evolving Facets of Bacterial Vaginosis: Implications for HIV Transmission","volume":"35","author":"LR McKinnon","year":"2019","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"2","key":"pone.0250153.ref034","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/00007435-200302000-00002","article-title":"A self-sampling method to obtain large volumes of undiluted cervicovaginal secretions","volume":"30","author":"E Boskey","year":"2003","journal-title":"Sex Transm Dis"},{"issue":"4","key":"pone.0250153.ref035","first-page":"249","article-title":"The maturation value","volume":"11","author":"A Meisels","year":"1967","journal-title":"Acta Cytol"},{"issue":"7","key":"pone.0250153.ref036","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1177\/22.7.492","article-title":"Acridine orange staining of epithelial cells in strong salt solution","volume":"22","author":"L Adams","year":"1974","journal-title":"J Histochem Cytochem"},{"issue":"4","key":"pone.0250153.ref037","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/gme.0b013e31824d8f40","article-title":"Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging","volume":"19","author":"SD Harlow","year":"2012","journal-title":"Menopause"},{"key":"pone.0250153.ref038","article-title":"Personal and Clinical Vaginal Lubricants: Impact on Local Vaginal Microenvironment and Implications for Epithelial Cell Host Response and Barrier Function","author":"EM Wilkinson","year":"2019","journal-title":"J Infect Dis"},{"issue":"1","key":"pone.0250153.ref039","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0378-5122(94)00863-3","article-title":"The vaginal epithelium in the postmenopause\u2014cytology, histology and pH as methods of assessment","volume":"21","author":"K Nilsson","year":"1995","journal-title":"Maturitas"},{"issue":"3","key":"pone.0250153.ref040","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/OLQ.0b013e31815abad8","article-title":"Application of optical coherence tomography for monitoring changes in cervicovaginal epithelial morphology in macaques: potential for assessment of microbicide safety","volume":"35","author":"KL Vincent","year":"2008","journal-title":"Sex Transm Dis"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T17:27:58Z","timestamp":1620062878000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250153"}},"subtitle":[],"editor":[{"given":"Rupert","family":"Kaul","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,5,3]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0250153","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2021,5,3]]}}}