{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:34:20Z","timestamp":1790642060367,"version":"4.1.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T00:00:00Z","timestamp":1444176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0139682","type":"journal-article","created":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T17:21:32Z","timestamp":1444238492000},"page":"e0139682","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":70,"title":["Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia"],"prefix":"10.1371","volume":"10","author":[{"given":"Alejandra","family":"Perez-Sepulveda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara J.","family":"Monteiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Dobierzewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro P.","family":"Espa\u00f1a-Perrot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00eda","family":"Venegas-Araneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra M.","family":"Guzm\u00e1n-Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda I.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Palominos-Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E.","family":"Irarrazabal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horacio","family":"Figueroa-Diesel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Varas-Godoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n E.","family":"Illanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,10,7]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1136\/bmj.39335.385301.BE","article-title":"Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis","volume":"335","author":"L Bellamy","year":"2007","journal-title":"BMJ"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1053\/j.semperi.2009.02.010","article-title":"The global impact of pre-eclampsia and eclampsia","volume":"33","author":"L Duley","year":"2009","journal-title":"Semin Perinatol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"477 e1","DOI":"10.1016\/j.ajog.2010.06.011","article-title":"Steroid profiling in preeclamptic women: evidence for aromatase deficiency","volume":"203","author":"A Hertig","year":"2010","journal-title":"Am J Obstet Gynecol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0140-6736(05)71003-5","article-title":"Pre-eclampsia","volume":"365","author":"B Sibai","year":"2005","journal-title":"Lancet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0140-6736(10)60279-6","article-title":"Pre-eclampsia","volume":"376","author":"EA Steegers","year":"2010","journal-title":"Lancet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.102.014977","article-title":"Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia","volume":"69","author":"P Kaufmann","year":"2003","journal-title":"Biol Reprod"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1586\/14737159.9.1.37","article-title":"Placentation abnormalities in the pathophysiology of preeclampsia","volume":"9","author":"MH Cheng","year":"2009","journal-title":"Expert Rev Mol Diagn"},{"issue":"Suppl A","key":"ref8","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1053\/plac.2002.0815","article-title":"Adriana and Luisa Castellucci Award lecture 2001. Hypoxia inducible factor\u20131: oxygen regulation of trophoblast differentiation in normal and pre-eclamptic pregnancies\u2013-a review","volume":"23","author":"I Caniggia","year":"2002","journal-title":"Placenta"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.2353\/ajpath.2007.061185","article-title":"Human placental hypoxia-inducible factor-1alpha expression correlates with clinical outcomes in chronic hypoxia in vivo","volume":"170","author":"S Zamudio","year":"2007","journal-title":"Am J Pathol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1210\/jc.2005-0078","article-title":"Molecular evidence of placental hypoxia in preeclampsia","volume":"90","author":"N Soleymanlou","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/OGX.0b013e3182331028","article-title":"A critical review of early-onset and late-onset preeclampsia","volume":"66","author":"D Raymond","year":"2011","journal-title":"Obstet Gynecol Surv"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.placenta.2009.02.009","article-title":"Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy","volume":"30","author":"GJ Burton","year":"2009","journal-title":"Placenta"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1477-7827-7-70","article-title":"Potential markers of preeclampsia\u2013-a review","volume":"7","author":"S Grill","year":"2009","journal-title":"Reprod Biol Endocrinol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jsgi.2004.03.003","article-title":"Placental oxidative stress: from miscarriage to preeclampsia","volume":"11","author":"GJ Burton","year":"2004","journal-title":"J Soc Gynecol Investig"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1161\/HYPERTENSIONAHA.113.02664","article-title":"Strategy for standardization of preeclampsia research study design","volume":"63","author":"L Myatt","year":"2014","journal-title":"Hypertension"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1161\/HYPERTENSIONAHA.107.107607","article-title":"Placental origins of preeclampsia: challenging the current hypothesis","volume":"51","author":"B Huppertz","year":"2008","journal-title":"Hypertension"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/ije\/dyg094","article-title":"Maternal serum oestrogen and androgen concentrations in preeclamptic and uncomplicated pregnancies","volume":"32","author":"R Troisi","year":"2003","journal-title":"Int J Epidemiol"},{"key":"ref18","first-page":"390","article-title":"The relationship between serum concentration of free testosterone and pre-eclampsia","volume":"59","author":"V Ghorashi","year":"2008","journal-title":"Endokrynol Pol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/pd.3954","article-title":"Low 2-methoxyestradiol levels at the first trimester of pregnancy are associated with the development of pre-eclampsia","volume":"32","author":"A Perez-Sepulveda","year":"2012","journal-title":"Prenat Diagn"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.0001-6349.2005.00493.x","article-title":"Early second-trimester maternal hyperandrogenemia and subsequent preeclampsia: a prospective study","volume":"84","author":"SM Carlsen","year":"2005","journal-title":"Acta Obstet Gynecol Scand"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/ki.2009.284","article-title":"The biology of preeclampsia","volume":"76","author":"K Kanasaki","year":"2009","journal-title":"Kidney Int"},{"key":"ref22","first-page":"126","article-title":"Aromatase research and its clinical significance","volume":"61","author":"I Czajka-Oraniec","year":"2010","journal-title":"Endokrynol Pol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1146\/annurev.physiol.64.081601.142703","article-title":"Aromatase\u2013-a brief overview","volume":"64","author":"ER Simpson","year":"2002","journal-title":"Annu Rev Physiol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1749-6632.2009.03703.x","article-title":"Molecular characterization of aromatase","volume":"1155","author":"Y Hong","year":"2009","journal-title":"Ann N Y Acad Sci"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"11071","DOI":"10.1158\/0008-5472.CAN-05-1218","article-title":"Human aromatase: gene resequencing and functional genomics","volume":"65","author":"CX Ma","year":"2005","journal-title":"Cancer Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1158\/1055-9965.EPI-06-1012","article-title":"Polymorphisms in the CYP19A1 (aromatase) gene and endometrial cancer risk in Chinese women","volume":"16","author":"MH Tao","year":"2007","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1210\/mend.14.10.0539","article-title":"Hypoxia prevents induction of aromatase expression in human trophoblast cells in culture: potential inhibitory role of the hypoxia-inducible transcription factor Mash\u20132 (mammalian achaete-scute homologous protein\u20132)","volume":"14","author":"B Jiang","year":"2000","journal-title":"Mol Endocrinol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/pd.4113","article-title":"First trimester prediction of early onset preeclampsia using demographic, clinical, and sonographic data: a cohort study","volume":"33","author":"J Caradeux","year":"2013","journal-title":"Prenat Diagn"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.placenta.2014.05.005","article-title":"Banking placental tissue: an optimized collection procedure for genome-wide analysis of nucleic acids","volume":"35","author":"LM Wolfe","year":"2014","journal-title":"Placenta"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1095\/biolreprod.109.077800","article-title":"Models for study of human embryo implantation: choice of cell lines?","volume":"82","author":"NJ Hannan","year":"2010","journal-title":"Biol Reprod"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.earlhumdev.2012.07.010","article-title":"Intrauterine growth restriction modifies the normal gene expression in kidney from rabbit fetuses","volume":"88","author":"H Figueroa","year":"2012","journal-title":"Early Hum Dev"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1177\/1933719113477483","article-title":"Metabolic pathways involved in 2-methoxyestradiol synthesis and their role in preeclampsia","volume":"20","author":"A Perez-Sepulveda","year":"2013","journal-title":"Reprod Sci"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/humupd\/dmp046","article-title":"Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy","volume":"16","author":"KG Pringle","year":"2010","journal-title":"Hum Reprod Update"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/nature06951","article-title":"Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia","volume":"453","author":"K Kanasaki","year":"2008","journal-title":"Nature"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"710","DOI":"10.2353\/ajpath.2010.090513","article-title":"Preeclampsia: 2-methoxyestradiol induces cytotrophoblast invasion and vascular development specifically under hypoxic conditions","volume":"176","author":"SB Lee","year":"2010","journal-title":"Am J Pathol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1016\/j.ajpath.2011.02.029","article-title":"Severe early-onset preeclampsia is not associated with a change in placental catechol O-methyltransferase (COMT) expression","volume":"178","author":"K Palmer","year":"2011","journal-title":"Am J Pathol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"731962","DOI":"10.1155\/2013\/731962","article-title":"Levels of key enzymes of methionine-homocysteine metabolism in preeclampsia","volume":"2013","author":"A Perez-Sepulveda","year":"2013","journal-title":"Biomed Res Int"},{"key":"ref38","first-page":"283","article-title":"Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy","volume":"80","author":"F Rodesch","year":"1992","journal-title":"Obstet Gynecol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/bjc.1998.92","article-title":"Inhibitors of aromatase prevent degradation of the enzyme in cultured human tumour cells","volume":"77","author":"N Harada","year":"1998","journal-title":"Br J Cancer"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1677\/erc.0.0060211","article-title":"Aromatase inhibitors and enzyme stability","volume":"6","author":"N Harada","year":"1999","journal-title":"Endocr Relat Cancer"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/biolreprod\/64.2.499","article-title":"Selective overexpression of the hypoxia-inducible transcription factor, HIF-2alpha, in placentas from women with preeclampsia","volume":"64","author":"A Rajakumar","year":"2001","journal-title":"Biol Reprod"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1095\/biolreprod.112.102723","article-title":"The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis","volume":"87","author":"R Tal","year":"2012","journal-title":"Biol Reprod"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1471-2407-10-36","article-title":"A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole","volume":"10","author":"Z Garcia-Casado","year":"2010","journal-title":"BMC Cancer"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1093\/jnci\/djh167","article-title":"Polymorphisms associated with circulating sex hormone levels in postmenopausal women","volume":"96","author":"AM Dunning","year":"2004","journal-title":"J Natl Cancer Inst"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1158\/0008-5472.CAN-09-3224","article-title":"Functional genetic polymorphisms in the aromatase gene CYP19 vary the response of breast cancer patients to neoadjuvant therapy with aromatase inhibitors","volume":"70","author":"L Wang","year":"2010","journal-title":"Cancer Res"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0139682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T21:54:43Z","timestamp":1540331683000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0139682"}},"subtitle":[],"editor":[{"given":"Sinuhe","family":"Hahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,10,7]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2015,10,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0139682","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,7]]}}}