{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:17:17Z","timestamp":1780319837034,"version":"3.54.1"},"reference-count":49,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD088868"],"award-info":[{"award-number":["HD088868"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD100529"],"award-info":[{"award-number":["HD100529"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD101852"],"award-info":[{"award-number":["HD101852"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004008","name":"National Institute of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004008","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","fertstert.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Fertility and Sterility"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.fertnstert.2021.05.081","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T02:39:11Z","timestamp":1623206351000},"page":"1160-1171","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":26,"title":["Tryptophan catabolism is dysregulated in leiomyomas"],"prefix":"10.1016","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-7054","authenticated-orcid":false,"given":"Tsai-Der","family":"Chuang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Quintanilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3094-2384","authenticated-orcid":false,"given":"Drake","family":"Boos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-5762","authenticated-orcid":false,"given":"Omid","family":"Khorram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.fertnstert.2021.05.081_bib1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/humupd\/dmt058","article-title":"Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations","volume":"20","author":"Segars","year":"2014","journal-title":"Hum Reprod Update"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib2","doi-asserted-by":"crossref","first-page":"16043","DOI":"10.1038\/nrdp.2016.43","article-title":"Uterine fibroids","volume":"2","author":"Stewart","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib3","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1111\/1471-0528.14640","article-title":"Epidemiology of uterine fibroids: a systematic review","volume":"124","author":"Stewart","year":"2017","journal-title":"Br J Obstet Gynaecol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib4","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S1071-55760300004-2","article-title":"Gene expression profile of leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy","volume":"10","author":"Chegini","year":"2003","journal-title":"J Soc Gynecol Investig"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib5","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1055\/s-0030-1251476","article-title":"Proinflammatory and profibrotic mediators: principal effectors of leiomyoma development as a fibrotic disorder","volume":"28","author":"Chegini","year":"2010","journal-title":"Semin Reprod Med"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib6","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1126\/science.1208930","article-title":"MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas","volume":"334","author":"Makinen","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0033251","article-title":"Whole exome sequencing in a random sample of North American women with leiomyomas identifies MED12 mutations in majority of uterine leiomyomas","volume":"7","author":"McGuire","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.tibs.2010.02.004","article-title":"The human mediator complex: a versatile, genome-wide regulator of transcription","volume":"35","author":"Taatjes","year":"2010","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib9","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1002\/ijc.27424","article-title":"MED12 mutations in uterine fibroids--their relationship to cytogenetic subgroups","volume":"131","author":"Markowski","year":"2012","journal-title":"Int J Cancer"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib10","first-page":"592","article-title":"Silencing Med12 gene reduces proliferation of human leiomyoma cells mediated via Wnt\/beta-catenin signaling pathway","volume":"158","author":"Al-Hendy","year":"2017","journal-title":"Endocrinology"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib11","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s43032-019-00084-7","article-title":"Introduction of somatic mutation in MED12 induces Wnt4\/\u03b2-catenin and disrupts autophagy in human uterine myometrial cell","volume":"27","author":"El Andaloussi","year":"2020","journal-title":"Reprod Sci"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib12","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.fertnstert.2018.01.034","article-title":"Next-generation sequencing reveals differentially expressed small noncoding RNAs in uterine leiomyoma","volume":"109","author":"Chuang","year":"2018","journal-title":"Fertil Steril"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib13","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1177\/1933719117711265","article-title":"Expression profiling of lncRNAs, miRNAs, and mRNAs and their differential expression in leiomyoma using next-generation RNA sequencing","volume":"25","author":"Chuang","year":"2018","journal-title":"Reprod Sci"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib14","doi-asserted-by":"crossref","DOI":"10.1177\/1178646917691938","article-title":"Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects","volume":"10","author":"Badawy","year":"2017","journal-title":"Int J Tryptophan Res"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib15","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.tips.2017.11.007","article-title":"Targeting the IDO1\/TDO2-KYN-AhR pathway forcancer immunotherapy \u2013 challenges and opportunities","volume":"39","author":"Cheong","year":"2018","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib16","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S0002-9378(16)33500-1","article-title":"Dating the endometrial biopsy","volume":"122","author":"Noyes","year":"1975","journal-title":"Am J Obstet Gynecol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib17","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1210\/me.2012-1075","article-title":"miR-93\/106b and their host gene, MCM7, are differentially expressed in leiomyomas and functionally target F3 and IL-8","volume":"26","author":"Chuang","year":"2012","journal-title":"Mol Endocrinol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib18","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1530\/ERC-12-0007","article-title":"miR-200c is aberrantly expressed in leiomyomas in an ethnic-dependent manner and targets ZEBs, VEGFA, TIMP2, and FBLN5","volume":"19","author":"Chuang","year":"2012","journal-title":"Endocr Relat Cancer"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib19","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ygyno.2014.04.012","article-title":"A high-throughput open-array qPCR gene panel to identify housekeeping genes suitable for myometrium and leiomyoma expression analysis","volume":"134","author":"Almeida","year":"2014","journal-title":"Gynecol Oncol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib20","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.fertnstert.2019.12.002","article-title":"Tranilast induces MiR-200c expression through blockade of RelA\/p65 activity in leiomyoma smooth muscle cells","volume":"113","author":"Chuang","year":"2020","journal-title":"Fertil Steril"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib21","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.fertnstert.2019.07.1324","article-title":"Cross-talk between miR-29c and transforming growth factor-\u03b23 is mediated by an epigenetic mechanism in leiomyoma","volume":"112","author":"Chuang","year":"2019","journal-title":"Fertil Steril"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib22","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.fertnstert.2020.07.024","article-title":"Functional role of the long noncoding RNA X-inactive specific transcript in leiomyoma pathogenesis","volume":"115","author":"Chuang","year":"2021","journal-title":"Fertil Steril"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib23","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1182\/blood-2009-09-246124","article-title":"Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity","volume":"115","author":"Liu","year":"2010","journal-title":"Blood"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib24","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1007\/s00432-020-03351-2","article-title":"Different effects of tryptophan 2,3-dioxygenase inhibition on SK-Mel-28 and HCT-8 cancer cell lines","volume":"146","author":"Paccosi","year":"2020","journal-title":"J Cancer Res Clin Oncol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib25","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1093\/humupd\/dmq053","article-title":"The role of mast cells and their mediators in reproduction, pregnancy and labour","volume":"17","author":"Menzies","year":"2011","journal-title":"Hum Reprod Update"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib26","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/jcp.1041460310","article-title":"Serotonin: an inducer of collagenase in myometrial smooth muscle cells","volume":"146","author":"Jeffrey","year":"1991","journal-title":"J Cell Physiol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib27","doi-asserted-by":"crossref","first-page":"25488","DOI":"10.1074\/jbc.273.39.25488","article-title":"Serotonin-mediated production of interstitial collagenase by uterine smooth muscle cells requires interleukin-1alpha, but not interleukin-1beta","volume":"273","author":"Dumin","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib28","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0303-7207(96)03827-0","article-title":"Serotonin regulation of gene expression in uterine extracellular matrix: reciprocal effects on collagens and collagenase","volume":"120","author":"Passaretti","year":"1996","journal-title":"Mol Cell Endocrinol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib29","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1530\/JOE-13-0429","article-title":"Differential expression and regulation of Tdo2 during mouse decidualization","volume":"220","author":"Li","year":"2013","journal-title":"J Endocrinol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib30","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/j.1460-2075.1987.tb04800.x","article-title":"Glucocorticoid induction of the rat tryptophan oxygenase gene is mediated by two widely separated glucocorticoid-responsive elements","volume":"6","author":"Danesch","year":"1987","journal-title":"EMBO J"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib31","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0021-9258(19)75845-1","article-title":"Multihormonal regulation of transcription of the tryptophan 2,3-dioxygenase gene in primary cultures of adult rat hepatocytes with special reference to the presence of a transcriptional protein mediating the action of glucocorticoids","volume":"262","author":"Nakamura","year":"1987","journal-title":"J Biol Chem"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib32","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1210\/endo-117-5-1788","article-title":"A new glucocorticoid receptor species: relation to induction of tryptophan dioxygenase by glucocorticoids","volume":"117","author":"Hirota","year":"1985","journal-title":"Endocrinology"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib33","doi-asserted-by":"crossref","first-page":"7533","DOI":"10.1016\/S0021-9258(19)43858-1","article-title":"Insulin and glucagon as a new regulator system for tryptophan oxygenase activity demonstrated in primary cultured rat hepatocytes","volume":"255","author":"Nakamura","year":"1980","journal-title":"J Biol Chem"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib34","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/abbi.2000.1755","article-title":"Heme: a regulator of rat hepatic tryptophan 2,3-dioxygenase?","volume":"377","author":"Ren","year":"2000","journal-title":"Arch Biochem Biophys"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib35","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1158\/0008-5472.CAN-15-2011","article-title":"A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer","volume":"75","author":"D'Amato","year":"2015","journal-title":"Cancer Res"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib36","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.3390\/ijms19123869","article-title":"The role of tumor necrosis factor \u03b1 in the biology of uterine fibroids and the related symptoms","volume":"19","author":"Ciebiera","year":"2018","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib37","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.fertnstert.2015.09.020","article-title":"Mechanisms underlying aberrant expression of miR-29c in uterine leiomyoma","volume":"105","author":"Chuang","year":"2016","journal-title":"Fertil Steril"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib38","first-page":"29","article-title":"Induction of TDO2 and IDO2 in liver by high-fat feeding in mice: discrepancies with human obesity","volume":"6","author":"Poulain-Godefroy","year":"2013","journal-title":"Int J Tryptophan Res"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib39","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1089\/jir.1986.6.267","article-title":"Characterization of an indoleamine 2,3-dioxygenase induced by gamma-interferon in cultured human fibroblasts","volume":"6","author":"Pfefferkorn","year":"1986","journal-title":"J Interferon Res"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib40","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/0006-291X(87)91431-8","article-title":"The actions of interferon and antiinflammatory agents of induction of indoleamine 2,3-dioxygenase in human peripheral blood monocytes","volume":"144","author":"Ozaki","year":"1987","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib41","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00441-015-2324-3","article-title":"Possible involvement of inflammatory\/reparative processes in the development of uterine fibroids","volume":"364","author":"Protic","year":"2016","journal-title":"Cell Tissue Res"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib42","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2016.03.014","article-title":"On the dependency of cellular protein levels on mRNA abundance","volume":"165","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib43","doi-asserted-by":"crossref","first-page":"8667","DOI":"10.1128\/MCB.00443-06","article-title":"Mediator modulates Gli3-dependent sonic hedgehog signaling","volume":"26","author":"Zhou","year":"2006","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib44","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.cell.2012.10.035","article-title":"MED12 controls the response to multiple cancer drugs through regulation of TGF-beta receptor signaling","volume":"151","author":"Huang","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib45","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature10491","article-title":"An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor","volume":"478","author":"Opitz","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib46","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1124\/dmd.115.064246","article-title":"Indole and tryptophan metabolism: endogenous and dietary routes to Ah receptor activation","volume":"43","author":"Hubbard","year":"2015","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib47","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1124\/mol.116.105361","article-title":"An aryl hydrocarbon receptor-mediated amplification loop that enforces cell migration in ER\u2212\/PR\u2212\/Her2\u2212 human breast cancer cells","volume":"90","author":"Novikov","year":"2016","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib48","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/jid.2013.303","article-title":"Kynurenine increases matrix metalloproteinase-1 and -3 expression in cultured dermal fibroblasts and improves scarring in\u00a0vivo","volume":"134","author":"Li","year":"2014","journal-title":"J Invest Dermatol"},{"key":"10.1016\/j.fertnstert.2021.05.081_bib49","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1002\/jcp.25383","article-title":"Kynurenine modulates MMP-1 and type-I collagen expression via aryl hydrocarbon receptor activation in dermal fibroblasts","volume":"231","author":"Poormasjedi-Meibod","year":"2016","journal-title":"J Cell Physiol"}],"container-title":["Fertility and Sterility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0015028221004349?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0015028221004349?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T06:16:44Z","timestamp":1762150604000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0015028221004349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["S0015028221004349"],"URL":"https:\/\/doi.org\/10.1016\/j.fertnstert.2021.05.081","relation":{},"ISSN":["0015-0282"],"issn-type":[{"value":"0015-0282","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Tryptophan catabolism is dysregulated in leiomyomas","name":"articletitle","label":"Article Title"},{"value":"Fertility and Sterility","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fertnstert.2021.05.081","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a92021 American Society for Reproductive Medicine, Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}