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The pathophysiology of endometriosis pain is not well understood and poorly correlated to stage. We hypothesized that this clinical heterogeneity may be explained by examining differences in gene expression. We performed RNA sequencing of 27 formalin-fixed, paraffin-embedded peritoneal biopsies from 9 symptomatic (Sx) and 10 asymptomatic (ASx) subjects. Eight hundred and ninety genes were differentially expressed between Sx and ASx samples. Of these, the most significant including genes involved inflammatory signaling (IL16, IL17RA, JAK3, SMPD3, RELT), cell adhesion (OLFML1, CDON, VCAN), and neuromodulation (SEMA6D, ADRA2C, SLC7A5). Gene set enrichment analysis identified functional enrichment in 22 gene ontology pathways, of which 7 represented immunologic pathways. Weighted gene correlation network analysis identified 11 co-expression modules significantly correlated with symptomaticity, including one module strongly enriched for immunologic\/inflammatory functions. Of all molecules identified as associated with pain, IL16 expression also correlated with symptom severity when cases were stratified into mild versus severe pain based on clinical criteria. These findings suggest that endometriotic lesions of symptomatic subjects are characterized by distinct molecular signatures, including altered expression of inflammatory pathways, highlighting potential mechanisms underlying symptom variability and identifying candidate pathways for future therapeutic interventions.<\/jats:p>","DOI":"10.1093\/molehr\/gaag055","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:48:48Z","timestamp":1788954528000},"source":"Crossref","is-referenced-by-count":0,"title":["Endometriosis pain: genes linked to inflammation distinguish symptomatic from asymptomatic disease"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4022-8910","authenticated-orcid":false,"given":"Ramanaiah","family":"Mamillapalli","sequence":"first","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J","family":"Li","sequence":"additional","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shant","family":"Apelian","sequence":"additional","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah F","family":"Wang","sequence":"additional","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishita","family":"Pondugula","sequence":"additional","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"de Queiroz Campos","sequence":"additional","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaiya","family":"Sayeed","sequence":"additional","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghee","family":"Cho","sequence":"additional","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh S","family":"Taylor","sequence":"additional","affiliation":[{"name":"Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine , New Haven, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"2026100810571227300_gaag055-B1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0015-0282(97)81391-X","article-title":"Revised American Society for Reproductive Medicine Classification of Endometriosis: 1996","volume":"67","author":"American Society For Reproductive Medicine","year":"1997","journal-title":"Fertil Steril"},{"key":"2026100810571227300_gaag055-B2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1055\/s-0036-1597123","article-title":"Relating chronic pelvic pain and endometriosis to signs of sensitization and myofascial pain and dysfunction","volume":"35","author":"Aredo","year":"2017","journal-title":"Semin Reprod Med"},{"key":"2026100810571227300_gaag055-B3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12974-023-02713-0","article-title":"Endometriosis leads to central nervous system-wide glial activation in a mouse model of endometriosis","volume":"20","author":"Bashir","year":"2023","journal-title":"J Neuroinflammation"},{"key":"2026100810571227300_gaag055-B4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1093\/humrep\/det401","article-title":"Can chemokines be used as biomarkers for endometriosis? 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