{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:29:14Z","timestamp":1760149754994,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Faculty of Saarland University","award":["HOMFOR 2021","282077667","411093008"],"award-info":[{"award-number":["HOMFOR 2021","282077667","411093008"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["HOMFOR 2021","282077667","411093008"],"award-info":[{"award-number":["HOMFOR 2021","282077667","411093008"]}]},{"name":"Saarland University Open Access Publishing program","award":["HOMFOR 2021","282077667","411093008"],"award-info":[{"award-number":["HOMFOR 2021","282077667","411093008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometriosis is a common gynecological disease which is characterized by endometriotic lesions outside the uterine cavity. In this study, we investigated whether the presence of pre-existing endometriotic lesions promotes the development of new lesions due to the exchange of cells and an altered peritoneal environment. For this purpose, uterine tissue samples from FVB\/N wild-type donor mice were transplanted simultaneously or time-delayed with samples from transgenic FVB-Tg(CAG-luc-GFP)L2G85Chco\/J donor mice into the abdominal cavity of FVB\/N wild-type recipient mice. The formation of endometriotic lesions was analyzed by means of high-resolution ultrasound, bioluminescence imaging, histology and immunohistochemistry. Moreover, immune cells and inflammatory factors in the peritoneal fluid were assessed by flow cytometry and a cytokine array. These analyses revealed that the growth of newly developing endometriotic lesions is promoted by the presence of pre-existing ones. This is not due to an exchange of cells between both lesion types but rather caused by peritoneal inflammation induced by already established lesions. These findings indicate that, among other pathogenic mechanisms, the chronic nature of endometriosis may be driven by a lesion-induced inflammatory milieu in the peritoneal cavity, which creates favorable conditions for the development of new lesions.<\/jats:p>","DOI":"10.3390\/ijms241813858","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T07:52:11Z","timestamp":1694159531000},"page":"13858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Presence of Pre-Existing Endometriotic Lesions Promotes the Growth of New Lesions in the Peritoneal Cavity"],"prefix":"10.3390","volume":"24","author":[{"given":"Ilinca T.","family":"Mihai","sequence":"first","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-2297","authenticated-orcid":false,"given":"Jeannette","family":"Rudzitis-Auth","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9670-7961","authenticated-orcid":false,"given":"Michael D.","family":"Menger","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7847-8456","authenticated-orcid":false,"given":"Matthias W.","family":"Laschke","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"446","DOI":"10.4103\/ijmr.IJMR_817_18","article-title":"A systematic review on the prevalence of endometriosis in women","volume":"154","author":"Moradi","year":"2021","journal-title":"Indian J. Med. Res."},{"key":"ref_2","first-page":"594","article-title":"Diagnosis and management of endometriosis","volume":"74","author":"Mounsey","year":"2006","journal-title":"Am. Fam. Physician"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1093\/humupd\/dmm010","article-title":"Endometriosis: Cost estimates and methodological perspective","volume":"13","author":"Simoens","year":"2007","journal-title":"Hum. Reprod. Update"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/j.fertnstert.2006.06.015","article-title":"Economic burden of endometriosis","volume":"86","author":"Gao","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0002-9378(15)30003-X","article-title":"Peritoneal endometriosis due to menstrual dissemination of endometrial tissues into the peritoneal cavity","volume":"14","author":"Sampson","year":"1927","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.fertnstert.2022.07.012","article-title":"Endometriosis caused by retrograde menstruation: Now demonstrated by DNA evidence","volume":"118","author":"Bulun","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jri.2016.01.005","article-title":"Promotion of angiogenesis and proliferation cytokines patterns in peritoneal fluid from women with endometriosis","volume":"116","author":"Rakhila","year":"2016","journal-title":"J. Reprod. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.fertnstert.2017.03.013","article-title":"Peritoneal fluid cytokines related to endometriosis in patients evaluated for infertility","volume":"107","author":"Hill","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1093\/biolre\/ioz039","article-title":"Endometrial cells contribute to preexisting endometriosis lesions in a mouse model of retrograde menstruation","volume":"100","author":"Tal","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.bpobgyn.2018.01.010","article-title":"Immunology of endometriosis","volume":"50","author":"Riccio","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4104","DOI":"10.1111\/bph.15601","article-title":"Targeting sphingosine kinase-1 with the low MW inhibitor SKI-5C suppresses the development of endometriotic lesions in mice","volume":"178","author":"Christoffel","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.2353\/ajpath.2006.051133","article-title":"A novel noninvasive model of endometriosis for monitoring the efficacy of antiangiogenic therapy","volume":"168","author":"Becker","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"dmm049070","DOI":"10.1242\/dmm.049070","article-title":"Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations","volume":"14","author":"Dorning","year":"2021","journal-title":"Dis. Models Mech."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1538\/expanim.21-0146","article-title":"Tracing location by applying Emerald luciferase in an early phase of murine endometriotic lesion formation","volume":"71","author":"Wibisono","year":"2022","journal-title":"Exp. Anim."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.fertnstert.2015.11.047","article-title":"Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients","volume":"105","author":"Monsanto","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1111\/all.13451","article-title":"Immunological and hematological effects of IL-5(R?)-targeted therapy: An overview","volume":"73","author":"Hassani","year":"2018","journal-title":"Allergy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jri.2011.05.008","article-title":"Increased Levels of Human Neutrophil Peptides 1, 2, and 3 in Peritoneal Fluid of Patients with Endometriosis: Association with Neutrophils, T Cells and IL-8","volume":"91","author":"Milewski","year":"2011","journal-title":"J. Reprod. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.molmed.2018.07.004","article-title":"The Immunopathophysiology of Endometriosis","volume":"24","author":"Symons","year":"2018","journal-title":"Trends Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1016\/j.fertnstert.2011.02.019","article-title":"T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal\/mild endometriosis","volume":"95","author":"Andreoli","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/jog.13559","article-title":"Involvement of immune cells in the pathogenesis of endometriosis","volume":"44","author":"Izumi","year":"2018","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"769","DOI":"10.7150\/ijms.71972","article-title":"IL-17: An important pathogenic factor in endometriosis","volume":"19","author":"Shi","year":"2022","journal-title":"Int. J. Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1210\/jc.2006-2486","article-title":"Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells","volume":"92","author":"Takemura","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","first-page":"E6892","article-title":"IL-4-secreting eosinophils promote endometrial stromal cell proliferation and prevent Chlamydia-induced upper genital tract damage","volume":"114","author":"Dixon","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rudzitis-Auth, J., Becker, M., Scheuer, C., Menger, M.D., and Laschke, M.W. (2022). Indole-3-Carbinol Inhibits the Growth of Endometriotic Lesions by Suppression of Microvascular Network Formation. Nutrients, 14.","DOI":"10.3390\/nu14224940"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5625","DOI":"10.1038\/s41598-022-09577-z","article-title":"The ischemic time window of ectopic endometrial tissue crucially determines its ability to develop into endometriotic lesions","volume":"12","author":"Huwer","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"585","DOI":"10.2353\/ajpath.2010.090617","article-title":"High-resolution ultrasound imaging: A novel technique for the noninvasive in vivo analysis of endometriotic lesion and cyst formation in small animal models","volume":"176","author":"Laschke","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/AOG.0000000000005255","article-title":"Barriers to a Timely Diagnosis of Endometriosis: A Qualitative Systematic Review","volume":"142","author":"Davenport","year":"2023","journal-title":"Obstet. Gynecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.cca.2022.11.013","article-title":"Non-invasive diagnosis of endometriosis: Immunologic and genetic markers","volume":"538","author":"Younesi","year":"2023","journal-title":"Clin. Chim. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1007\/s10815-020-01905-4","article-title":"GRN, NOTCH3, FN1, and PINK1 expression in eutopic endometrium\u2014Potential biomarkers in the detection of endometriosis\u2014A pilot study","volume":"37","author":"Holzer","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"900","DOI":"10.3390\/cimb43020064","article-title":"Circulating miRNAs Related to Epithelial-Mesenchymal Transitions (EMT) as the New Molecular Markers in Endometriosis","volume":"43","author":"Zubrzycka","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cuccu, I., D\u2019Oria, O., Sgamba, L., De Angelis, E., Golia D\u2019Aug\u00e8, T., Turetta, C., Di Dio, C., Scudo, M., Bogani, G., and Di Donato, V. (2023). Role of Genomic and Molecular Biology in the Modulation of the Treatment of Endometrial Cancer: Narrative Review and Perspectives. Healthcare, 11.","DOI":"10.3390\/healthcare11040571"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13858\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:47:31Z","timestamp":1760129251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,8]]},"references-count":31,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241813858"],"URL":"https:\/\/doi.org\/10.3390\/ijms241813858","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,9,8]]}}}