{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T14:43:59Z","timestamp":1781966639936,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972441"],"award-info":[{"award-number":["81972441"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072883"],"award-info":[{"award-number":["82072883"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Ovary is a common organ site involved by endometriosis. We previously found that fallopian tube may contribute to the histogenesis of ovarian endometriosis. The finding was novel and requires further studies. We addressed this issue by examining a differentially expressed gene folate receptor alpha (<jats:italic>FOLR1<\/jats:italic>) and its protein (FRA) in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 144 tissue samples were studied. These included 32-paired tubal-endometrial-ovarian endometriosis samples (<jats:italic>n<\/jats:italic> =\u200996), 18 samples of ovarian endometriosis without corresponding fallopian tube or endometrium, and 30 ovarian tissue samples with ovarian surface epithelia but without endometriosis. Multiple comparisons among groups of ovarian endometriosis, normal fallopian tube and benign endometrium were performed. <jats:italic>FOLR1<\/jats:italic> was highly expressed in the epithelia of fallopian tube and ovarian endometriosis, with paired endometrial samples showing a significantly lower level of expression. Similar differential studies for FRA protein were performed through Western blot and immunohistochemistry (IHC). The expression of folate receptor alpha at both mRNA and protein levels in the tissues (fallopian tube or ovarian endometriosis vs. the endometrium) were significantly different (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.001). All ovarian surface mesothelial epithelia showed negative expression of FRA by IHC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results further support that the fallopian tube may contribute to the development of ovarian endometriosis. Understanding the tubal contribution to ovarian endometriosis should ultimately contribute to ongoing investigative efforts aimed at identifying alternative ways to prevent and treat endometriosis. High level of FRA expression in the fallopian tube and endometriosis might be considered as potential tissue sites for targeted therapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1138690","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T04:27:06Z","timestamp":1677731226000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Fallopian tubal histogenesis of ovarian endometriosis\u2014A study of folate receptor-alpha expression"],"prefix":"10.3389","volume":"10","author":[{"given":"Yiying","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijiao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry Y.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanrun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeng","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwole","family":"Fadare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0002-9378(15)30003-X","article-title":"Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity","volume":"14","author":"Sampson","year":"1927","journal-title":"Am J Obstet Gynecol"},{"key":"ref2","first-page":"151","article-title":"Retrograde menstruation in healthy women and in patients with endometriosis","volume":"64","author":"Halme","year":"1984","journal-title":"Obstet Gynecol"},{"key":"ref3","first-page":"6","article-title":"The current question of adenomyositis and adenomyomas in general and particularly Seroepithelial adenomyositis and Sarcomatoid adenomyometritis","volume":"43","author":"Meyer","year":"1919","journal-title":"Zentralbl Gynakol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1097\/01.RCT.0000157091.37057.B4","article-title":"Initial endometriosis showing direct morphologic evidence of metaplasia in the pathogenesis of ovarian endometriosis","volume":"24","author":"Zheng","year":"2005","journal-title":"Int J Gynecol Pathol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1038\/modpathol.2011.106","article-title":"Tubal origin of \u2018ovarian\u2019 low-grade serous carcinoma. Modern pathology: an official journal of the United States and Canadian academy of pathology","volume":"24","author":"Li","year":"2011","journal-title":"Inc"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.fertnstert.2018.10.013","article-title":"Pathogenesis of endometriosis: the genetic\/epigenetic theory","volume":"111","author":"Koninckx","year":"2019","journal-title":"Fertil Steril"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1756-8722-5-8","article-title":"Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis","volume":"5","author":"Li","year":"2012","journal-title":"J Hematol Oncol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.ajog.2004.02.067","article-title":"Intraperitoneal serous adenocarcinoma: a critical appraisal of three hypotheses on its cause","volume":"191","author":"Piek","year":"2004","journal-title":"Am J Obstet Gynecol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ygyno.2017.04.015","article-title":"Frequency of \u201cincidental\u201d serous tubal intraepithelial carcinoma (STIC) in women without a history of or genetic risk factor for high-grade serous carcinoma: a six-year study","volume":"146","author":"Meserve","year":"2017","journal-title":"Gynecol Oncol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1038\/modpathol.2013.245","article-title":"Tubal origin of ovarian endometriosis. Modern pathology: an official journal of the United States and Canadian academy of pathology","volume":"27","author":"Yuan","year":"2014","journal-title":"Inc"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/00006254-196801000-00001","article-title":"The histogenesis of endometriosis","volume":"23","author":"Ridley","year":"1968","journal-title":"Obstet Gynecol Surv"},{"key":"ref12","first-page":"615","article-title":"The histogenesis of endometriosis; recent contributions","volume":"1","author":"Gardner","year":"1953","journal-title":"Obstet Gynecol"},{"key":"ref13","first-page":"869","article-title":"Tubal origin of ovarian endometriosis and clear cell and endometrioid carcinoma","volume":"5","author":"Wang","year":"2015","journal-title":"Am J Cancer Res"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.18632\/oncotarget.412","article-title":"Characterization of the human folate receptor alpha via novel antibody-based probes","volume":"2","author":"O\u2019Shannessy","year":"2011","journal-title":"Oncotarget"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1097\/PGP.0b013e3182774562","article-title":"Expression of folate receptor-alpha (FRA) in gynecologic malignancies and its relationship to the tumor type","volume":"32","author":"O\u2019Shannessy","year":"2013","journal-title":"Int J Gynecol Pathol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1016\/S0140-6736(04)17403-5","article-title":"Endometriosis","volume":"364","author":"Giudice","year":"2004","journal-title":"Lancet"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-pathmechdis-012419-032654","article-title":"The origin and pathogenesis of endometriosis","volume":"15","author":"Wang","year":"2020","journal-title":"Annu Rev Pathol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/jcm9061905","article-title":"Cell origin of endometriosis: contribution by the fallopian tube epithelium","volume":"1","author":"Yuan","year":"2013","journal-title":"Am J Clin Exp Obstet Gynecol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1097\/PAS.0b013e3181cf3d79","article-title":"The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory","volume":"34","author":"Kurman","year":"2010","journal-title":"Am J Surg Pathol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1097\/PAS.0b013e3181868904","article-title":"Serous tubal intraepithelial carcinoma and the dominant ovarian mass: clues to serous tumor origin?","volume":"33","author":"Roh","year":"2009","journal-title":"Am J Surg Pathol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1097\/00003081-198012000-00023","article-title":"Anatomy and physiology of the fallopian tube","volume":"23","author":"Eddy","year":"1980","journal-title":"Clin Obstet Gynecol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1093\/humrep\/13.6.1425","article-title":"Endoscopic visualization of the process of fimbrial ovum retrieval in the human","volume":"13","author":"Gordts","year":"1998","journal-title":"Hum Reprod"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/S0140-6736(01)05992-X","article-title":"Tubal ligation and risk of ovarian cancer","volume":"358","author":"Piek","year":"2001","journal-title":"Lancet"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.ygyno.2007.11.020","article-title":"Folate receptor alpha as a tumor target in epithelial ovarian cancer","volume":"108","author":"Kalli","year":"2008","journal-title":"Gynecol Oncol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/B978-0-12-380864-6.00004-3","article-title":"Folate and one-carbon metabolism and its impact on aberrant DNA methylation in cancer","volume":"71","author":"Liu","year":"2010","journal-title":"Adv Genet"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1002\/ijc.24723","article-title":"Relationship between dietary and supplemental intake of folate, methionine, vitamin B6 and folate receptor alpha expression in ovarian tumors","volume":"126","author":"Kotsopoulos","year":"2010","journal-title":"Int J Cancer"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1757-2215-6-29","article-title":"Serum folate receptor alpha, mesothelin and megakaryocyte potentiating factor in ovarian cancer: association to disease stage and grade and comparison to CA125 and HE4","volume":"6","author":"O\u2019Shannessy","year":"2013","journal-title":"J Ovarian Res"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e0122209","DOI":"10.1371\/journal.pone.0122209","article-title":"Folate receptor-alpha (FOLR1) expression and function in triple negative tumors","volume":"10","author":"Necela","year":"2015","journal-title":"PLoS One"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1002\/ijc.29937","article-title":"Serum folate receptor alpha as a biomarker for ovarian cancer: implications for diagnosis, prognosis and predicting its local tumor expression","volume":"138","author":"Kurosaki","year":"2016","journal-title":"Int J Cancer"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2918","DOI":"10.1093\/humrep\/der274","article-title":"The post-reproductive fallopian tube: better removed?","volume":"26","author":"Dietl","year":"2011","journal-title":"Hum Reprod"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/S0140-6736(71)92335-X","article-title":"Incessant ovulation--a factor in ovarian neoplasia?","volume":"2","author":"Fathalla","year":"1971","journal-title":"Lancet"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1093\/humrep\/den358","article-title":"Ovarian epithelial dysplasia after ovulation induction: time and dose effects","volume":"24","author":"Chene","year":"2009","journal-title":"Hum Reprod"},{"key":"ref33","first-page":"310","article-title":"Endosalpingiosis of the peritoneum","volume":"34","author":"Burmeister","year":"1969","journal-title":"Obstet Gynecol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"57s","DOI":"10.1097\/00006250-198003001-00019","article-title":"Endosalpingiosis","volume":"55","author":"Tutschka","year":"1980","journal-title":"Obstet Gynecol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1002\/jcb.240590928","article-title":"Pathology of ovarian cancer precursors","volume":"23","author":"Scully","year":"1995","journal-title":"J Cell Biochem Suppl"},{"key":"ref36","first-page":"784","article-title":"Epithelial metaplastic changes in ovarian endometriosis. Modern pathology: an official journal of the United States and Canadian academy of pathology","volume":"11","author":"Fukunaga","year":"1998","journal-title":"Inc"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1159\/000052874","article-title":"Malignant transformation of ovarian endometriosis","volume":"50","author":"Nishida","year":"2000","journal-title":"Gynecol Obstet Investig"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41571-020-0339-5","article-title":"Exploiting the folate receptor alpha in oncology","volume":"17","author":"Scaranti","year":"2020","journal-title":"Nat Rev Clin Oncol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ijgo.2012.10.025","article-title":"Analysis of biomarker expression in severe endometriosis and determination of possibilities for targeted intraoperative imaging","volume":"121","author":"van den Berg","year":"2013","journal-title":"Int J Gynaecol Obstet"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e22566","DOI":"10.1371\/journal.pone.0022566","article-title":"Calcium prevents tumorigenesis in a mouse model of colorectal cancer","volume":"6","author":"Wang","year":"2011","journal-title":"PLoS One"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/j.1447-0756.2011.01695.x","article-title":"Alteration of HGF and TSP-1 expression in ovarian carcinoma associated with clinical features","volume":"38","author":"Wei","year":"2012","journal-title":"J Obstet Gynaecol Res"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.3892\/or.2012.1641","article-title":"53BP1 suppresses tumor growth and promotes susceptibility to apoptosis of ovarian cancer cells through modulation of the Akt pathway","volume":"27","author":"Hong","year":"2012","journal-title":"Oncol Rep"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1138690\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T04:27:13Z","timestamp":1677731233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1138690\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":42,"alternative-id":["10.3389\/fmed.2023.1138690"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2023.1138690","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,2]]},"article-number":"1138690"}}