{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:16:59Z","timestamp":1788171419473,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Society of Reproductive Endocrinology and Infertility (SREI) Young Investigator Award"},{"id":[{"id":"https:\/\/ror.org\/00d3y5a88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: The objective of this exploratory study was to test the hypothesis that endometriosis is associated with altered abundance and cellular location of nuclear progesterone receptor (PR) isoforms in eutopic endometrium. Methods: Immunohistochemistry (IHC) was used to compare total PR (PR-A\/B), PR-B, and pSer344\/345-PR staining in endometrium from patients with and without endometriosis and between eutopic endometrium and ectopic endometriotic lesions in patients with endometriosis. Reproductive-age female patients undergoing laparoscopy for endometriosis (n = 10), or for other indications and without a diagnosis of endometriosis (n = 10), were included in this case\u2013control study. Results: Eutopic endometrium from patients with endometriosis demonstrated increased total PR (PR-A\/B) staining relative to PR-B staining compared with patients without endometriosis; a similar staining pattern was observed in ectopic lesions. Because PR-A was not measured directly and the total PR and PR-B antibodies may differ in affinity and dynamic range, these findings provide indirect evidence of altered relative PR isoform abundance rather than direct demonstration of a PR-A-dominant state. pSer344\/345-PR staining did not differ significantly between groups, although a nonsignificant trend toward higher staining was observed in endometriosis. Conclusions: These preliminary findings support further study of PR isoform balance and site-specific phosphorylation in progesterone resistance associated with endometriosis.<\/jats:p>","DOI":"10.3390\/jcm15176664","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:21:19Z","timestamp":1788168079000},"page":"6664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered Progesterone Receptor Isoform Expression in Endometrial Cells: A Preliminary Immunohistochemical Study in Endometriosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7413-4111","authenticated-orcid":false,"given":"Kathryn","family":"Coyne","sequence":"first","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Chloe Van","family":"Dorn","sequence":"additional","affiliation":[{"name":"School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8658-8396","authenticated-orcid":false,"given":"Sung Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Joseph","family":"Findley","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Rebecca","family":"Flyckt","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3981-5317","authenticated-orcid":false,"given":"Sam","family":"Mesiano","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Rachel","family":"Weinerman","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1210\/endo.143.6.8885","article-title":"Global gene profiling in human endometrium during the window of implantation","volume":"143","author":"Kao","year":"2002","journal-title":"Endocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1210\/endo.140.10.7070","article-title":"Progesterone receptor regulates decidual prolactin expression in differentiating human endometrial stromal cells","volume":"140","author":"Brosens","year":"1999","journal-title":"Endocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0015-0282(03)00982-8","article-title":"Steroid receptor and aromatase expression in baboon endometriotic lesions","volume":"80","author":"Fazleabas","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/rmb2.12088","article-title":"Decidualization of the human endometrium","volume":"17","author":"Okada","year":"2018","journal-title":"Reprod. Med. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Marquardt, R.M., Kim, T.H., Shin, J.H., and Jeong, J.W. (2019). Progesterone and estrogen signaling in the endometrium: What goes wrong in endometriosis?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153822"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0015-0282(16)60545-9","article-title":"Immunohistochemical analysis of estrogen and progesterone receptors in endometriosis: Comparison with normal endometrium during the menstrual cycle and the effect of medical therapy","volume":"51","author":"Lessey","year":"1989","journal-title":"Fertil. Steril."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0015-0282(16)48376-7","article-title":"Steroidal regulation of endometriosis tissue: Lack of induction of 17 beta-hydroxysteroid dehydrogenase activity by progesterone, medroxyprogesterone acetate, or danazol","volume":"43","author":"Vierikko","year":"1985","journal-title":"Fertil. Steril."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.mce.2005.11.041","article-title":"Progesterone resistance in endometriosis: Link to failure to metabolize estradiol","volume":"248","author":"Bulun","year":"2006","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_9","first-page":"2897","article-title":"Progesterone receptor isoform A but not B is expressed in endometriosis","volume":"85","author":"Attia","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1126\/science.3283939","article-title":"The steroid and thyroid hormone receptor superfamily","volume":"240","author":"Evans","year":"1988","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1002\/j.1460-2075.1990.tb08280.x","article-title":"Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B","volume":"9","author":"Kastner","year":"1990","journal-title":"EMBO J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1128\/MCB.20.9.3102-3115.2000","article-title":"The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding","volume":"20","author":"Giangrande","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"ref_13","first-page":"1256","article-title":"Antagonist-occupied human progesterone B-receptors activate transcription without binding to progesterone response elements and are dominantly inhibited by A-receptors","volume":"7","author":"Tung","year":"1993","journal-title":"Mol. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1093\/molehr\/7.9.875","article-title":"Interactions between progesterone receptor isoforms in myometrial cells in human labour","volume":"7","author":"Pieber","year":"2001","journal-title":"Mol. Hum. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5209","DOI":"10.1074\/jbc.M110090200","article-title":"Differential gene regulation by the two progesterone receptor isoforms in human breast cancer cells","volume":"277","author":"Richer","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1210\/me.2005-0242","article-title":"Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-kappaB may contribute to the onset of labor through inhibition of PR function","volume":"20","author":"Condon","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1210\/jc.2007-0077","article-title":"Nuclear progesterone receptors in the human pregnancy myometrium: Evidence that parturition involves functional progesterone withdrawal mediated by increased expression of progesterone receptor-A","volume":"92","author":"Merlino","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1056\/NEJMra0804690","article-title":"Endometriosis","volume":"360","author":"Bulun","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1177\/1933719115585145","article-title":"Abundance and localization of progesterone receptor isoforms in endometrium in women with and without endometriosis and in peritoneal and ovarian endometriotic implants","volume":"22","author":"Bedaiwy","year":"2015","journal-title":"Reprod. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1097\/PAI.0000000000000663","article-title":"Human endometriosis tissue microarray reveals site-specific expression of estrogen receptors, progesterone receptor, and Ki67","volume":"27","author":"Mendoza","year":"2019","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.fertnstert.2005.01.113","article-title":"Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"84","author":"Igarashi","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_22","first-page":"1","article-title":"Altered expression of progesterone receptor isoforms A and B in human eutopic endometrium in endometriosis patients","volume":"206","author":"Rath","year":"2016","journal-title":"Ann. Anat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00404-014-3419-x","article-title":"Decreased expression of mucin-1 in endometriosis endometrium correlated with progesterone receptor B involved in infertility","volume":"291","author":"Shen","year":"2015","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1210\/en.2018-00374","article-title":"miR-194-3p represses the progesterone receptor and decidualization in eutopic endometrium from women with endometriosis","volume":"159","author":"Pei","year":"2018","journal-title":"Endocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/aogs.13156","article-title":"Progesterone resistance in endometriosis: Origins, consequences and interventions","volume":"96","author":"Patel","year":"2017","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1093\/oxfordjournals.humrep.a137848","article-title":"Ovarian steroid receptor expression in endometriosis and in two potential parent epithelia: Endometrium and peritoneal mesothelium","volume":"7","author":"Prentice","year":"1992","journal-title":"Hum. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.mce.2011.10.035","article-title":"Mechanisms of endometrial progesterone resistance","volume":"358","author":"Lam","year":"2012","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/humupd\/dmu056","article-title":"Role of nuclear progesterone receptor isoforms in uterine pathophysiology","volume":"21","author":"Patel","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1210\/me.2007-0437","article-title":"Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors","volume":"22","author":"Faivre","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1210\/mend.14.1.0413","article-title":"Differential hormone-dependent phosphorylation of progesterone receptor A and B forms revealed by a phosphoserine site-specific monoclonal antibody","volume":"14","author":"Clemm","year":"2000","journal-title":"Mol. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1210\/en.2016-1654","article-title":"Human Parturition Involves Phosphorylation of Progesterone Receptor-A at Serine-345 in Myometrial Cells","volume":"157","author":"Amini","year":"2016","journal-title":"Endocrinology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1136\/jcp.54.8.624","article-title":"Detection of progesterone receptor forms A and B by immunohistochemical analysis","volume":"54","author":"Mote","year":"2001","journal-title":"J. Clin. Pathol."},{"key":"ref_33","first-page":"127","article-title":"The effect of imbalanced progesterone receptor-A\/-B ratio on gelatinase expressions in endometriosis","volume":"13","author":"Mousazadeh","year":"2019","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1210\/clinem\/dgac118","article-title":"Progesterone receptor status of epithelial cells as a predictive marker for postoperative recurrence of endometriosis","volume":"107","author":"Tarumi","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"110743","DOI":"10.1016\/j.mce.2020.110743","article-title":"Progesterone\u2019s role in deep infiltrating endometriosis: Progesterone receptor and estrogen metabolism enzymes expression and physiological changes in primary endometrial stromal cell culture","volume":"505","author":"Kamergorodsky","year":"2020","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1210\/en.2018-00990","article-title":"Phosphorylated progesterone receptor isoforms mediate opposing stem cell and proliferative breast cancer cell fates","volume":"160","author":"Truong","year":"2019","journal-title":"Endocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1210\/jc.2003-031037","article-title":"Prostaglandins differentially modulate progesterone receptor-A and -B expression in human myometrial cells: Evidence for prostaglandin-induced functional progesterone withdrawal","volume":"89","author":"Madsen","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"You, Y., Chen, Y., Fang, W., Li, X., Wang, R., Liu, J., and Ma, X. (2023). The association between sedentary behavior, exercise, and sleep disturbance: A mediation analysis of inflammatory biomarkers. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1080782"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6664\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:37:46Z","timestamp":1788169066000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15176664"],"URL":"https:\/\/doi.org\/10.3390\/jcm15176664","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}