{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:40:26Z","timestamp":1790109626505,"version":"4.0.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"This project was supported by intramural funds from the Faculty of Medicine, University of Southampton (INC &amp;#x2013; PI account)."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Chlamydia trachomatis<\/jats:italic> (Ct) is the leading cause of bacterial sexually transmitted infections worldwide and has been associated with male infertility. Recently, it was hypothesized that Ct may infect the epithelium of the seminiferous tubule, formed by Sertoli cells, thus leading to impaired spermatogenesis. To date, there is a lack of data on Ct infection of the seminiferous epithelium; therefore, we aimed to characterize, for the first time, an <jats:italic>in vitro<\/jats:italic> infection model of primary human Sertoli cells. We compared Ct inclusion size, morphology and growth kinetics with those in McCoy cells and we studied F-actin fibres, Vimentin-based intermediate filaments and \u03b1-tubulin microtubules in Sertoli and McCoy cells. Our main finding highlighted the ability of Ct to infect Sertoli cells, although with a unique growth profile and the inability to exit host cells. Furthermore, we observed alterations in the cytoskeletal fibres of infected Sertoli cells. Our results suggest that Ct struggles to generate a productive infection in Sertoli cells, limiting its dissemination in the host. Nevertheless, the adverse effect on the cytoskeleton supports the notion that Ct may compromise the blood-testis barrier, impairing spermatogenesis.<\/jats:p>","DOI":"10.1038\/s41598-019-42396-3","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T10:18:48Z","timestamp":1554891528000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Growth kinetics of Chlamydia trachomatis in primary human Sertoli cells"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-8588","authenticated-orcid":false,"given":"Simone","family":"Filardo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel J.","family":"Skilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette E.","family":"O\u2019Neill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Di Pietro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Sessa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian N.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,10]]},"reference":[{"key":"42396_CR1","doi-asserted-by":"publisher","unstructured":"Sessa, R., et al. Lactobacilli-lactoferrin interplay in Chlamydia trachomatis infection. Pathog Dis. 75(5), https:\/\/doi.org\/10.1093\/femspd\/ftx054 (2017).","DOI":"10.1093\/femspd\/ftx054"},{"issue":"1","key":"42396_CR2","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1139\/bcb-2016-0049","volume":"95","author":"R Sessa","year":"2017","unstructured":"Sessa, R. et al. Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation. Biochem Cell Biol. 95(1), 34\u201340, https:\/\/doi.org\/10.1139\/bcb-2016-0049 (2017).","journal-title":"Biochem Cell Biol."},{"issue":"12","key":"42396_CR3","doi-asserted-by":"publisher","first-page":"e0143304","DOI":"10.1371\/journal.pone.0143304","volume":"10","author":"L Newman","year":"2015","unstructured":"Newman, L. et al. Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting. PLoS One. 10(12), e0143304, https:\/\/doi.org\/10.1371\/journal.pone.0143304 (2015).","journal-title":"PLoS One."},{"issue":"1-2","key":"42396_CR4","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.jri.2009.07.007","volume":"83","author":"S Bhushan","year":"2009","unstructured":"Bhushan, S., Schuppe, H. C., Fijak, M. & Meinhardt, A. Testicular infection: microorganisms, clinical implications and host-pathogen interaction. J Reprod Immunol. 83(1\u20132), 164\u2013167, https:\/\/doi.org\/10.1016\/j.jri.2009.07.007 (2009).","journal-title":"J Reprod Immunol."},{"issue":"9","key":"42396_CR5","doi-asserted-by":"publisher","first-page":"390","DOI":"10.15698\/mic2016.09.525","volume":"3","author":"CM O\u2019Connell","year":"2016","unstructured":"O\u2019Connell, C. M. & Ferone, M. E. Chlamydia trachomatis Genital Infections. Microb Cell. 3(9), 390\u2013403, https:\/\/doi.org\/10.15698\/mic2016.09.525 (2016).","journal-title":"Microb Cell."},{"issue":"3","key":"42396_CR6","doi-asserted-by":"publisher","first-page":"188","DOI":"10.4103\/iju.IJU_407_16","volume":"33","author":"M Solomon","year":"2017","unstructured":"Solomon, M. & Henkel, R. Semen culture and the assessment of genitourinary tract infections. Indian J Urol. 33(3), 188\u2013193, https:\/\/doi.org\/10.4103\/iju.IJU_407_16 (2017).","journal-title":"Indian J Urol."},{"key":"42396_CR7","doi-asserted-by":"publisher","unstructured":"Vander Borght, M. & Wyns, C. Fertility and infertility: Definition and epidemiology. Clin Biochem. pii: S0009-9120(18)30220-0. https:\/\/doi.org\/10.1016\/j.clinbiochem.2018.03.012 (2018).","DOI":"10.1016\/j.clinbiochem.2018.03.012"},{"issue":"12","key":"42396_CR8","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/nrurol.2014.285","volume":"11","author":"F Gimenes","year":"2014","unstructured":"Gimenes, F. et al. Male infertility: a public health issue caused by sexually transmitted pathogens. Nat Rev Urol. 11(12), 672\u2013687, https:\/\/doi.org\/10.1038\/nrurol.2014.285 (2014).","journal-title":"Nat Rev Urol."},{"issue":"4","key":"42396_CR9","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.euf.2016.08.002","volume":"2","author":"M Fode","year":"2016","unstructured":"Fode, M., Fusco, F., Lipshultz, L. & Weidner, W. Sexually Transmitted Disease and Male Infertility: A Systematic Review. Eur Urol Focus. 2(4), 383\u2013393, https:\/\/doi.org\/10.1016\/j.euf.2016.08.002 (2016).","journal-title":"Eur Urol Focus."},{"issue":"1","key":"42396_CR10","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1093\/humrep\/dei269","volume":"21","author":"A Satta","year":"2006","unstructured":"Satta, A. et al. Experimental Chlamydia trachomatis infection causes apoptosis in human sperm. Hum Reprod. 21(1), 134\u2013137 (2006).","journal-title":"Hum Reprod."},{"key":"42396_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/srep24583","volume":"6","author":"AM O\u2019Doherty","year":"2016","unstructured":"O\u2019Doherty, A. M., Di Fenza, M., K\u00f6lle, S. & Lipopolysaccharide, L. P. S. disrupts particle transport, cilia function and sperm motility in an ex vivo oviduct model. Sci Rep. 6, 24583, https:\/\/doi.org\/10.1038\/srep24583 (2016).","journal-title":"Sci Rep."},{"issue":"9","key":"42396_CR12","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1093\/humrep\/dei082","volume":"20","author":"A Eley","year":"2005","unstructured":"Eley, A., Hosseinzadeh, S., Hakimi, H., Geary, I. & Pacey, A. A. Apoptosis of ejaculated human sperm is induced by co-incubation with Chlamydia trachomatis lipopolysaccharide. Hum Reprod. 20(9), 2601\u20132607 (2005).","journal-title":"Hum Reprod."},{"key":"42396_CR13","doi-asserted-by":"publisher","unstructured":"Ahmadi, M. H., Mirsalehian, A., Sadighi Gilani, M. A., Bahador, A., Afraz, K. Association of asymptomatic Chlamydia trachomatis infection with male infertility and the effect of antibiotic therapy in improvement of semen quality in infected infertile men. Andrologia, https:\/\/doi.org\/10.1111\/and.12944 (2018).","DOI":"10.1111\/and.12944"},{"issue":"5","key":"42396_CR14","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1177\/0956462417735245","volume":"29","author":"M Moazenchi","year":"2018","unstructured":"Moazenchi, M. et al. The impact of Chlamydia trachomatis infection on sperm parameters and male fertility: A comprehensive study. Int J STD AIDS. 29(5), 466\u2013473, https:\/\/doi.org\/10.1177\/0956462417735245 (2018).","journal-title":"Int J STD AIDS."},{"issue":"7","key":"42396_CR15","doi-asserted-by":"publisher","first-page":"e98903","DOI":"10.1371\/journal.pone.0098903","volume":"9","author":"H Sellami","year":"2014","unstructured":"Sellami, H. et al. Molecular detection of Chlamydia trachomatis and other sexually transmitted bacteria in semen of male partners of infertile couples in Tunisia: the effect on semen parameters and spermatozoa apoptosis markers. PLoS One. 9(7), e98903, https:\/\/doi.org\/10.1371\/journal.pone.0098903 (2014).","journal-title":"PLoS One."},{"issue":"1","key":"42396_CR16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1095\/biolreprod.114.124180","volume":"92","author":"AP Sobinoff","year":"2015","unstructured":"Sobinoff, A. P. et al. Chlamydia muridarum infection-induced destruction of male germ cells and sertoli cells is partially prevented by Chlamydia major outer membrane protein-specific immune CD4 cells. Biol Reprod. 92(1), 27, https:\/\/doi.org\/10.1095\/biolreprod.114.124180 (2015).","journal-title":"Biol Reprod."},{"issue":"5","key":"42396_CR17","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1210\/er.2014-1101","volume":"36","author":"DD Mruk","year":"2015","unstructured":"Mruk, D. D. & Cheng, C. Y. The Mammalian Blood-Testis Barrier: Its Biology and Regulation. Endocr Rev. 36(5), 564\u2013591, https:\/\/doi.org\/10.1210\/er.2014-1101 (2015).","journal-title":"Endocr Rev."},{"issue":"4","key":"42396_CR18","doi-asserted-by":"publisher","first-page":"504","DOI":"10.14310\/horm.2002.1648","volume":"14","author":"PK Iliadou","year":"2015","unstructured":"Iliadou, P. K., Tsametis, C., Kaprara, A., Papadimas, I. & Goulis, D. G. The Sertoli cell: Novel clinical potentiality. Hormones (Athens). 14(4), 504\u2013514, https:\/\/doi.org\/10.14310\/horm.2002.1648 (2015).","journal-title":"Hormones (Athens)."},{"issue":"2","key":"42396_CR19","doi-asserted-by":"publisher","first-page":"e979106","DOI":"10.4161\/21565562.2014.979106","volume":"4","author":"KJ Johnson","year":"2014","unstructured":"Johnson, K. J. Testicular histopathology associated with disruption of the Sertoli cell cytoskeleton. Spermatogenesis. 4(2), e979106 (2014).","journal-title":"Spermatogenesis."},{"key":"42396_CR20","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/978-1-4939-7698-0_16","volume":"1748","author":"Q Wen","year":"2018","unstructured":"Wen, Q. et al. Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and Microtubule-Based Cytoskeletons. Methods Mol Biol. 1748, 229\u2013243, https:\/\/doi.org\/10.1007\/978-1-4939-7698-0_16 (2018).","journal-title":"Methods Mol Biol."},{"issue":"3","key":"42396_CR21","first-page":"256","volume":"67","author":"D Taylor-Robinson","year":"1991","unstructured":"Taylor-Robinson, D. & Thomas, B. J. Laboratory techniques for the diagnosis of chlamydial infections. Genitourin Med. 67(3), 256\u201366 (1991).","journal-title":"Genitourin Med."},{"issue":"4","key":"42396_CR22","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1136\/jcp.2004.021543","volume":"58","author":"JM Lyons","year":"2005","unstructured":"Lyons, J. M., Ito, J. I. Jr, Pe\u00f1a, A. S. & Morr\u00e9, S. A. Differences in growth characteristics and elementary body associated cytotoxicity between Chlamydia trachomatis oculogenital serovars D and H and Chlamydia muridarum. J Clin Pathol. 58(4), 397\u2013401 (2005).","journal-title":"J Clin Pathol."},{"issue":"3","key":"42396_CR23","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1128\/IAI.01118-10","volume":"79","author":"CM O\u2019Connell","year":"2011","unstructured":"O\u2019Connell, C. M. et al. Toll-like receptor 2 activation by Chlamydia trachomatis is plasmid dependent, and plasmid-responsive chromosomal loci are coordinately regulated in response to glucose limitation by C. trachomatis but not by C. muridarum. Infect Immun. 79(3), 1044\u201356, https:\/\/doi.org\/10.1128\/IAI.01118-10 (2011).","journal-title":"Infect Immun."},{"issue":"5","key":"42396_CR24","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1007\/s10096-008-0650-z","volume":"28","author":"M Donati","year":"2009","unstructured":"Donati, M. et al. Chlamydia trachomatis serovar distribution and other concurrent sexually transmitted infections in heterosexual men with urethritis in Italy. Eur J Clin Microbiol Infect Dis. 28(5), 523\u2013526, https:\/\/doi.org\/10.1007\/s10096-008-0650-z (2009).","journal-title":"Eur J Clin Microbiol Infect Dis."},{"issue":"4","key":"42396_CR25","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1097\/OLQ.0b013e3181fc6944","volume":"38","author":"J Twin","year":"2011","unstructured":"Twin, J. et al. Chlamydia trachomatis genotypes among men who have sex with men in Australia. Sex Transm Dis. 38(4), 279\u2013285, https:\/\/doi.org\/10.1097\/OLQ.0b013e3181fc6944 (2011).","journal-title":"Sex Transm Dis."},{"key":"42396_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-3","volume":"14","author":"SP Verweij","year":"2014","unstructured":"Verweij, S. P. et al. Serovar D and E of serogroup B induce highest serological responses in urogenital Chlamydia trachomatis infections. BMC Infect Dis. 14, 3, https:\/\/doi.org\/10.1186\/1471-2334-14-3 (2014).","journal-title":"BMC Infect Dis."},{"key":"42396_CR27","doi-asserted-by":"publisher","first-page":"25","DOI":"10.12688\/wellcomeopenres.13905.1","volume":"3","author":"RJ Skilton","year":"2018","unstructured":"Skilton, R. J. et al. The Chlamydia muridarum plasmid revisited: new insights into growth kinetics. Wellcome Open Res. 3, 25, https:\/\/doi.org\/10.12688\/wellcomeopenres.13905.1 (2018).","journal-title":"Wellcome Open Res."},{"issue":"Pt 3","key":"42396_CR28","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1099\/mic.0.27625-0","volume":"151","author":"MA Pickett","year":"2005","unstructured":"Pickett, M. A., Everson, J. S., Pead, P. J. & Clarke, I. N. The plasmids of Chlamydia trachomatis and Chlamydophila pneumoniae (N16): accurate determination of copy number and the paradoxical effect of plasmid-curing agents. Microbiology. 151(Pt 3), 893\u2013903 (2005).","journal-title":"Microbiology."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42396-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42396-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42396-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T08:31:12Z","timestamp":1671265872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42396-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,10]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["42396"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-42396-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,10]]},"assertion":[{"value":"6 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"5847"}}