{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:20:41Z","timestamp":1773663641644,"version":"3.50.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Deep infiltrating endometriosis (DIE) is a severe subtype of endometriosis, often associated with dysmenorrhea and significant diagnostic challenges. Conventional biomarkers, such as cancer antigen 125 (CA125), lack sufficient specificity for accurate DIE diagnosis. Estrogen receptor \u03b136 (ER\u03b136) is a novel isoform of the estrogen receptor, distinct from the classic estrogen receptor \u03b166 (ER\u03b166), and has been implicated in the pathogenesis of several gynecologic disorders, including breast and endometrial cancer. However, the expression pattern of\n                      <jats:italic>ER\u03b136<\/jats:italic>\n                      in DIE tissues and its potential role as a diagnostic biomarker for DIE have not yet been investigated. This study aimed to examine the expression of\n                      <jats:italic>ER\u03b136<\/jats:italic>\n                      in DIE tissues, explore its association with disease presence, and evaluate its potential as a diagnostic biomarker and a candidate for future therapeutic targeting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A case-control study was conducted between 2014 and 2016, enrolling 80 DIE patients as the case group and 132 healthy women as the control group. The expression of ER\u03b136 was evaluated at both the mRNA and protein levels: reverse transcription-polymerase chain reaction was used for mRNA expression and immunohistochemistry was performed for protein detection. Statistical analyses were performed using SPSS version 26.0, and receiver operating characteristic curve analysis was employed to assess the diagnostic performance of ER\u03b136 for DIE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No significant differences were observed between control and endometriosis groups in demographic or reproductive characteristics (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt;0.05). ER\u03b136 mRNA was detected in 71.2% of endometriosis tissues, compared with 36.4% of controls (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.01). Among 80 patients with endometriosis, ER\u03b136 expression was observed in 57 cases and absent in 23. ER\u03b136-positive patients exhibited younger age, higher rFAS (revised American Fertility Society) stage, more severe and longer-lasting dysmenorrhea, increased absenteeism during menstruation, greater adnexal adhesions, and a higher prevalence of DIE (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). Protein gene product 9.5 (PGP9.5) was present in eutopic endometrium, with significantly higher density in DIE lesions compared with ovarian and superficial peritoneal endometriosis (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.01). Notably, ER\u03b136-positive patients showed a higher proportion of strong\n                      <jats:italic>PGP9.5<\/jats:italic>\n                      expression than ER\u03b136-negative patients (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). These findings indicate that\n                      <jats:italic>ER\u03b136<\/jats:italic>\n                      expression is associated with more severe disease phenotypes and increased neural marker expression in endometriosis, particularly in DIE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ER\u03b136 is highly expressed in DIE tissues and exhibits good diagnostic performance with high sensitivity and specificity. These findings suggest that ER\u03b136 may serve as a novel tissue-level biomarker for DIE, representing a potential target for future therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1752870","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:36:09Z","timestamp":1773207369000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between estrogen receptor alpha 36 expression and the risk of deep infiltrating endometriosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Embryo Original Diseases","place":["Shanghai, China"]},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiantian","family":"Yu","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Embryo Original Diseases","place":["Shanghai, China"]},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunbo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstrics and Gynecology, The First People\u2019s Hospital of Jiande","place":["Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruihong","family":"Xue","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Embryo Original Diseases","place":["Shanghai, China"]},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1093\/humrep\/deu290","article-title":"Protein oxidative stress markers in peritoneal fluids of women with deep infiltrating endometriosis are increased","volume":"30","author":"Santulli","year":"2015","journal-title":"Hum Reprod"},{"key":"B2","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.fertnstert.2017.08.036","article-title":"Pathogenesis of deep endometriosis","volume":"108","author":"Gordts","year":"2017","journal-title":"Fertil 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