{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:42:13Z","timestamp":1792460533024,"version":"4.5.0"},"reference-count":145,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:p>Endometriosis is an estrogen-dependent chronic inflammatory syndrome characterized by viable endometrial tissue outside the uterine cavity and associated with pain and infertility. Endometriosis, as tissue or a pathological process, is dynamic in that its establishment and progression require repeated episodes of retrograde travel of shed endometrial tissue, which implants in the lower abdominal cavity following ovulatory cycles and survives. Estrogen-rich follicular fluid released onto peritoneal surfaces during ovulation may also support endometriotic implants. DNA evidence indicates that endometriosis originates from eutopic endometrial tissue, which may reach the abdominal cavity in a retrograde manner primarily via the uterine tubes. Unlike uterine bleeding associated with non-ovulatory circumstances, retrograde menstruation following an ovulation maximizes shedding of epithelial cells localized to deep invaginations of the basalis portion of the endometrium, which likely carry somatic cancer-driver mutations such as KRAS. The attached endometrial stromal cells are mostly mutation free but display epigenetic defects including overexpression of aromatase and estrogen receptor-\u03b2 and downregulation of progesterone receptor, causing estrogen excess and progesterone resistance. These tissue clones may form implants in involuting ovarian corpus luteum cysts and peritoneal surfaces and induce tissue remodeling and fibrosis, manifested as deep-infiltrating endometriosis. The first-line treatment for chronic pelvic pain associated with endometriosis is suppression of ovulation, with the goal of relieving pain. Infertility is often managed using in vitro fertilization, which improves the embryo quality and alters endometrial development.<\/jats:p>","DOI":"10.1172\/jci188787","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T14:00:34Z","timestamp":1751292034000},"source":"Crossref","is-referenced-by-count":28,"title":["Endometriosis and ovulatory menstruation: beyond the Sampson principle"],"prefix":"10.1172","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0850-8637","authenticated-orcid":true,"given":"Serdar E.","family":"Bulun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoae045"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dead229"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.12.039"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0245-z"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1810764"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00389-5"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.7.8683"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(98)00022-3"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)44409-2"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(97)81391-X"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(97)81392-1"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2018.06.003"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoac009"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.255"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-2115(00)00265-7"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10061403"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2019.10.007"},{"issue":"2","key":"B18","article-title":"Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation","volume":"3","author":"Sampson","year":"1927","journal-title":"Am J Pathol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(15)30003-X"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(40)91238-8"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14507"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.037"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/path.5778"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu330"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13708-y"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2023.03.006"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmab017"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000002978"},{"key":"B29","article-title":"Dysmenorrhoea","volume":"2014","author":"Latthe","year":"2014","journal-title":"BMJ Clin Evid"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(01)02981-8"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1597306"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.99"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.08.008"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00242"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804690"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e318299a6cf"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-018-0667-3"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des073"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0223316"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-021-06243-z"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-35236-y"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2023.11.034"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/8.1.84"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00794"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2022.07.012"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2022.05.030"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.34.1170"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2010.009321"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dep275"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dei368"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2006.12.078"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3399\/bjgp24X737685"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-019-03419-3"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh035"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1597308"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dead206"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.806574"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1177\/1933719108322430"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2016.07.041"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2013.08.007"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/eva.13244"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.xagr.2023.100259"},{"key":"B63"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/0020-7292(89)90541-9"},{"key":"B65"},{"key":"B66"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-8-117"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(94)90070-1"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2008.02055.x"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j3778"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.05.035"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2006.01.016"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(96)80086-X"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcped.2013.04.010"},{"key":"B75","unstructured":"Hartmann KE, et al. Primary Care Management of Abnormal Uterine Bleeding. Agency for Healthcare Research and Quality, Rockville, Maryland, USA. 2013. https:\/\/effectivehealthcare.ahrq.gov\/sites\/default\/files\/pdf\/abnormal-uterine-bleeding_research.pdf Accessed May 14, 2025"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2005.06.044"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.17812"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2024.104345"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deae086"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2023.07.033"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.whi.2024.03.004"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.1.81"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0828"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2012.03064.x"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1177\/1066896913501385"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614814"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2214-z"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwg177"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1002\/path.4516"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117569"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.12.4474"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2005.11.041"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.12.0742"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0459"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1536"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der172"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.8.2897"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.02.158"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0043"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gan036"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1210\/jc.78.3.642"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.2.600"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1177\/1933719118756751"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1692"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2005.08.046"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1210\/jc.81.1.174"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1210\/mend.13.2.0229"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004158"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0494"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.107.061804"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmz005"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa070"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2015.06.046"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.116.140434"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008601"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05070-z"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1177\/1933719113497267"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1210\/jc.76.6.1458"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1180"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1466"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.106.051912"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab150"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10051085"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28608-x"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.106.059451"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2076"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1242996"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.7.3263"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201347200"},{"issue":"2","key":"B130","first-page":"189","article-title":"Peritoneal fluid volume, estrogen, progesterone, prostaglandin, and epidermal growth factor concentrations in patients with and without endometriosis","volume":"68","author":"De Leon","year":"1986","journal-title":"Obstet Gynecol"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)48194-X"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2004.02.007"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2006.05.068"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(99)00393-3"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2003.09.076"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.11.022"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507931112"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2023.106734"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des313"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det041"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.10.022"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMct0803719"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1700089"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00622-5"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1097\/00006250-200205000-00008"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/188787\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:16:53Z","timestamp":1779211013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/188787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":145,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,5,13]]},"published-print":{"date-parts":[[2025,7,1]]}},"alternative-id":["10.1172\/JCI188787"],"URL":"https:\/\/doi.org\/10.1172\/jci188787","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"article-number":"e188787"}}