{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:04:37Z","timestamp":1792569877129,"version":"4.5.0"},"posted":{"date-parts":[[2026,4,24]]},"group-title":"Pathology","reference-count":20,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["1R01DK124067"],"award-info":[{"award-number":["1R01DK124067"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21AI138255-01"],"award-info":[{"award-number":["R21AI138255-01"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,24]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n \n Benign Prostatic Hyperplasia (BPH) is the non-cancerous enlargement of the prostate accompanied by lower urinary tract symptoms, affecting 50% of men by the age of 50\n 1,2<\/jats:sup>\n . Advanced highly symptomatic BPH exhibits large epithelial glandular nodules with microglandular\/atypical adenomatous hyperplasia, but how these features form is unknown\n 3<\/jats:sup>\n . Our lab has reported that the common parasite\n Toxoplasma gondii<\/jats:italic>\n can infect the prostate and induce glandular nodule formation in mice\n 3<\/jats:sup>\n . The objective of this study is to determine if\n T. gondii<\/jats:italic>\n exposure in humans correlates to BPH and nodule formation and if it induces urinary dysfunction concurrent in the mouse model.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We assessed\n Toxoplasma<\/jats:italic>\n exposure by serum ELISA in patients with BPH and non-BPH donor controls, and compared seropositivity rates between the groups. We further assessed the histopathology of these patients for the presence of inflammation and epithelial glandular nodule formation and compared\n Toxoplasma<\/jats:italic>\n positive and negative samples. We determined voiding function in\n Toxoplasma<\/jats:italic>\n -infected mice between 14 and 60 days of infection with void spot with Void Whizzard software.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Men diagnosed with BPH are more likely to be seropositive for\n Toxoplasma<\/jats:italic>\n than age-matched undiagnosed donor controls. In addition, BPH patients that are seropositive for\n Toxoplasma<\/jats:italic>\n are more likely to exhibit glandular nodule formation with microglandular \/ adenomous hyperplasia than seronegative\n BPH patients<\/jats:italic>\n . In animal studies,\n Toxoplasma<\/jats:italic>\n infection results in abnormal void patterns concurrent with microglandular hyperplasia and nodule formation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These results suggest that\n Toxoplasma<\/jats:italic>\n may be contributing to BPH pathology and lower urinary tract dysfunction in both humans and mice, opening new insights into the development of this important disease. The results also serve to further characterize this model of prostatic hyperplasia and define it as a potential urinary dysfunction model.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.64898\/2026.04.23.720409","type":"posted-content","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T21:15:13Z","timestamp":1777065313000},"source":"Crossref","is-referenced-by-count":3,"title":["Toxoplasma gondii<\/i>\n associates with human Benign Prostatic Hyperplasia and induces prostatic hyperplasia and accompanying urinary dysfunction in mice"],"prefix":"10.64898","author":[{"given":"Emily F.","family":"Stanczak","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology\u2014Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara D.","family":"Fuller","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology\u2014Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doug W.","family":"Strand","sequence":"additional","affiliation":[{"name":"Department of Urology\u2014University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology\u2014Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver R.","family":"Strobel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology\u2014Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene Heredero","family":"Bermejo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Biotechnology \u2014Universidad de Alcal\u00e1, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-927X","authenticated-orcid":false,"given":"Gustavo","family":"Arrizabalaga","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology--Jacobs School of Medicine & Biomedical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis J.","family":"Jerde","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology\u2014Indiana University School of Medicine, Indianapolis, IN"},{"name":"Department of Pharmacology and Toxicology\u2014Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026042804550849000_2026.04.23.720409v1.1","unstructured":"Simon HB. Prostate Enlargement (Benign Prostatic Hyperplasia). National Institute of Diabetes and Digestive and Kidney Disease. https:\/\/www.niddk.nih.gov\/health-information\/urologic-diseases\/prostate-problems\/prostate-enlargement-benign-prostatic-hyperplasia#whatIs."},{"key":"2026042804550849000_2026.04.23.720409v1.2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000152318.79184.6f"},{"issue":"3","key":"2026042804550849000_2026.04.23.720409v1.3","first-page":"S11","article-title":"Pathology of benign prostatic hyperplasia","volume":"20","year":"2008","journal-title":"Int J Impot Res"},{"key":"2026042804550849000_2026.04.23.720409v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23362"},{"key":"2026042804550849000_2026.04.23.720409v1.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090203"},{"issue":"14","key":"2026042804550849000_2026.04.23.720409v1.6","doi-asserted-by":"crossref","first-page":"R770","DOI":"10.1016\/j.cub.2018.05.035","article-title":"Toxoplasma gondii","volume":"28","year":"2018","journal-title":"Curr Biol."},{"key":"2026042804550849000_2026.04.23.720409v1.7","unstructured":"Dubey JP. Toxoplasma Gondii . In: Baron S , editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996."},{"key":"2026042804550849000_2026.04.23.720409v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21433"},{"key":"2026042804550849000_2026.04.23.720409v1.9","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s10555-022-10072-0","article-title":"Circadian disruption: from mouse models to molecular mechanisms and cancer therapeutic targets","volume":"42","year":"2023","journal-title":"Cancer Metastasis Rev"},{"key":"2026042804550849000_2026.04.23.720409v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2011.04.006"},{"key":"2026042804550849000_2026.04.23.720409v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2020.12.001"},{"issue":"11","key":"2026042804550849000_2026.04.23.720409v1.12","first-page":"117001","volume":"126","year":"2018","journal-title":"Evaluation of Bisphenol A (BPA) Exposures on Prostate Stem Cell Homeostasis and Prostate Cancer Risk in the NCTR-Sprague-Dawley Rat: An NIEHS\/FDA CLARITY-BPA Consortium Study"},{"key":"2026042804550849000_2026.04.23.720409v1.13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00350.2018"},{"issue":"1","key":"2026042804550849000_2026.04.23.720409v1.14","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/s42003-024-07071-y","article-title":"Inflammation impacts androgen receptor signaling in basal prostate stem cells through interleukin 1 receptor antagonist","volume":"7","year":"2024","journal-title":"Commun Biol"},{"key":"2026042804550849000_2026.04.23.720409v1.15","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.218693"},{"issue":"1","key":"2026042804550849000_2026.04.23.720409v1.16","doi-asserted-by":"crossref","first-page":"F118","DOI":"10.1152\/ajprenal.00213.2025","article-title":"Macrophages and TGFB signaling regulate fibrosis in the Escherichia coli-infected mouse prostate","volume":"330","year":"2026","journal-title":"Am J Physiol Renal Physiol"},{"issue":"6","key":"2026042804550849000_2026.04.23.720409v1.17","doi-asserted-by":"crossref","first-page":"360","DOI":"10.62347\/ATKI4166","article-title":"Mechanisms of prostatic inflammation-mediated male lower urinary tract symptoms","volume":"13","year":"2025","journal-title":"Am J Clin Exp Urol"},{"key":"2026042804550849000_2026.04.23.720409v1.18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00602.2015"},{"issue":"2","key":"2026042804550849000_2026.04.23.720409v1.19","doi-asserted-by":"crossref","first-page":"e0341745","DOI":"10.1371\/journal.pone.0341745","article-title":"Risk of prostatitis in patients with type 2 diabetes mellitus: An observational retrospective cohort study of canagliflozin versus other antihyperglycemic agents using propensity score matching","volume":"21","year":"2026","journal-title":"PLoS One"},{"issue":"4","key":"2026042804550849000_2026.04.23.720409v1.20","doi-asserted-by":"crossref","first-page":"261","DOI":"10.5213\/inj.2244190.095","article-title":"Oxidative Stress and Its Relation to Lower Urinary Tract Symptoms","volume":"26","year":"2022","journal-title":"Int Neurourol J"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.23.720409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:55:20Z","timestamp":1777377320000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.23.720409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":20,"URL":"https:\/\/doi.org\/10.64898\/2026.04.23.720409","relation":{},"subject":[],"published":{"date-parts":[[2026,4,24]]},"subtype":"preprint"}}