{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:08:49Z","timestamp":1790431729682,"version":"4.1.0"},"reference-count":43,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":1598,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P50 HD055764"],"award-info":[{"award-number":["P50 HD055764"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R37 HD076253"],"award-info":[{"award-number":["R37 HD076253"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sara Borrell Programme Fellowship","award":["CD14\/00229"],"award-info":[{"award-number":["CD14\/00229"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Preeclampsia (PE), which affects \u223c8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs normally up regulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g., placental proteins, markers of oxidative stress). We confirmed a sPE-related increase in production of PAPPA1, which releases IGF-1 from its binding protein. IGF1 enhanced proliferation of smooth chorion CTBs, a possible explanation for expansion of this layer, which may partially compensate for the placental deficits.<\/jats:p>","DOI":"10.1242\/dev.146100","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T01:11:01Z","timestamp":1487898661000},"source":"Crossref","is-referenced-by-count":18,"title":["Severe preeclampsia is associated with alterations in cytotrophoblasts of the smooth chorion"],"prefix":"10.1242","author":[{"given":"T.","family":"Garrido-Gomez","sequence":"first","affiliation":[{"name":"Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"},{"name":"Fundaci\u00f3n Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI, INCLIVA, Valencia University, Valencia, Spain"},{"name":"Igenomix, Parc Cientific Universidad de Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Ona","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kapidzic","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Gormley","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Sim\u00f3n","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI, INCLIVA, Valencia University, Valencia, Spain"},{"name":"Igenomix, Parc Cientific Universidad de Valencia, Valencia, Spain"},{"name":"Department of Obstetrics and Gynecology, School of Medicine, Stanford University, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Genbacev","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7745-4850","authenticated-orcid":false,"given":"S. J.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA"},{"name":"The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, CA 94143, USA"},{"name":"Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042609080970100_DEV146100C1","first-page":"573","article-title":"Experimental toxemia of pregnancy in the monkey, with a preliminary report on renin and aldosterone","volume":"86","author":"Abitbol","year":"1977","journal-title":"Am. J. Pathol."},{"key":"2021042609080970100_DEV146100C2","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1161\/HYPERTENSIONAHA.114.04484","article-title":"17-hydroxyprogesterone caproate significantly improves clinical characteristics of preeclampsia in the reduced uterine perfusion pressure rat model","volume":"65","author":"Amaral","year":"2015","journal-title":"Hypertension"},{"key":"2021042609080970100_DEV146100C3","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1159\/000147695","article-title":"Studies of hemidesmosomes in human amnion: the use of a detergent extraction protocol for compositional and ultrastructural analysis and preparation of a hemidesmosome-enriched fraction from tissue","volume":"152","author":"Behzad","year":"1995","journal-title":"Acta Anat."},{"key":"2021042609080970100_DEV146100C4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-642-23941-0","volume-title":"Pathology of the Human Placenta","author":"Benirschke","year":"2012"},{"key":"2021042609080970100_DEV146100C5","first-page":"Pvi","article-title":"The role of the spiral arteries in the pathogenesis of pre-eclampsia","volume":"101","author":"Brosens","year":"1970","journal-title":"J. Pathol."},{"key":"2021042609080970100_DEV146100C6","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/j.1600-0897.1989.tb01009.x","article-title":"Expression of epidermal growth factor receptor and transferrin receptor by human trophoblast populations","volume":"21","author":"Bulmer","year":"1989","journal-title":"Am. J. Reprod. Immunol."},{"key":"2021042609080970100_DEV146100C7","first-page":"S6.e1","article-title":"What is the placenta?","volume":"213","author":"Burton","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2021042609080970100_DEV146100C8","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1387\/ijdb.082764gb","article-title":"The influence of the intrauterine environment on human placental development","volume":"54","author":"Burton","year":"2010","journal-title":"Int. J. Dev. Biol."},{"key":"2021042609080970100_DEV146100C9","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1242\/dev.120.12.3657","article-title":"Integrin switching regulates normal trophoblast invasion","volume":"120","author":"Damsky","year":"1994","journal-title":"Development"},{"key":"2021042609080970100_DEV146100C10","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1053\/plac.2001.0626","article-title":"Structure of anchoring villi and the trophoblastic shell in the human, baboon and macaque placenta","volume":"22","author":"Enders","year":"2001","journal-title":"Placenta"},{"key":"2021042609080970100_DEV146100C11","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1083\/jcb.109.2.891","article-title":"Adhesive and degradative properties of human placental cytotrophoblast cells in vitro","volume":"109","author":"Fisher","year":"1989","journal-title":"J. Cell Biol."},{"key":"2021042609080970100_DEV146100C12","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1053\/plac.2000.0573","article-title":"Does plasminogen activator inhibitor-1 (PAI-1) control trophoblast invasion? A study of fetal and maternal tissue in intrauterine, tubal and molar pregnancies","volume":"21","author":"Floridon","year":"2000","journal-title":"Placenta"},{"key":"2021042609080970100_DEV146100C13","doi-asserted-by":"publisher","first-page":"2701","DOI":"10.1016\/j.bbagen.2012.11.002","article-title":"IGF dependent modulation of IGF binding protein (IGFBP) proteolysis by pregnancy-associated plasma protein-A (PAPP-A): multiple PAPP-A-IGFBP interaction sites","volume":"1830","author":"Gaidamauskas","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"2021042609080970100_DEV146100C14","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.placenta.2015.05.002","article-title":"The role of chorionic cytotrophoblasts in the smooth chorion fusion with parietal decidua","volume":"36","author":"Genbacev","year":"2015","journal-title":"Placenta"},{"key":"2021042609080970100_DEV146100C15","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1093\/humrep\/dew077","article-title":"Integrin alpha4-positive human trophoblast progenitors: functional characterization and transcriptional regulation","volume":"31","author":"Genbacev","year":"2016","journal-title":"Hum. Reprod."},{"key":"2021042609080970100_DEV146100C16","first-page":"383","article-title":"Reduced uterine perfusion pressure (RUPP) model for studying cardiovascular-renal dysfunction in response to placental ischemia","volume":"122","author":"Granger","year":"2006","journal-title":"Methods Mol. Med."},{"key":"2021042609080970100_DEV146100C17","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1515\/JPEM.2000.13.4.343","article-title":"The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development","volume":"13","author":"Handwerger","year":"2000","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"2021042609080970100_DEV146100C18","doi-asserted-by":"publisher","first-page":"6456","DOI":"10.4049\/jimmunol.1003691","article-title":"Guanylate binding protein 4 negatively regulates virus-induced type I IFN and antiviral response by targeting IFN regulatory factor 7","volume":"187","author":"Hu","year":"2011","journal-title":"J. Immunol."},{"key":"2021042609080970100_DEV146100C19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000299115","article-title":"Cellular proliferation in villi of normal and pathological pregnancies","volume":"17","author":"Hustin","year":"1984","journal-title":"Gynecol. Obstet. Invest."},{"key":"2021042609080970100_DEV146100C20","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s00441-014-2037-z","article-title":"The biology and regulation of corneodesmosomes","volume":"360","author":"Ishida-Yamamoto","year":"2015","journal-title":"Cell Tissue Res."},{"key":"2021042609080970100_DEV146100C21","doi-asserted-by":"publisher","first-page":"33061","DOI":"10.1074\/jbc.M104539200","article-title":"Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones","volume":"276","author":"Johansson","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021042609080970100_DEV146100C22","doi-asserted-by":"publisher","first-page":"3057","DOI":"10.1073\/pnas.87.8.3057","article-title":"Human trophoblast-extracellular matrix (ECM) interactions in vitro: ECM thickness modulates morphology and proteolytic activity","volume":"87","author":"Kliman","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042609080970100_DEV146100C23","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.placenta.2015.11.004","article-title":"Differential expression of human placental PAPP-A2 over gestation and in preeclampsia","volume":"37","author":"Kramer","year":"2016","journal-title":"Placenta"},{"key":"2021042609080970100_DEV146100C24","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.chom.2016.02.019","article-title":"Guanylate Binding Protein (GBP) 5 is an interferon-inducible inhibitor of HIV-1 infectivity","volume":"19","author":"Krapp","year":"2016","journal-title":"Cell Host Microbe"},{"key":"2021042609080970100_DEV146100C25","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/0143-4004(87)90036-1","article-title":"Peroxidase-labelled lectin binding of human extravillous trophoblast","volume":"8","author":"Lalani","year":"1987","journal-title":"Placenta"},{"key":"2021042609080970100_DEV146100C26","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/S0143-4004(05)80386-8","article-title":"Regional distribution of the angiotensinogens in human placentae","volume":"14","author":"Lenz","year":"1993","journal-title":"Placenta"},{"key":"2021042609080970100_DEV146100C27","first-page":"1809","article-title":"Human cytotrophoblast differentiation\/invasion is abnormal in pre-eclampsia","volume":"151","author":"Lim","year":"1997","journal-title":"Am. J. Pathol."},{"key":"2021042609080970100_DEV146100C28","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1146\/annurev-cellbio-100814-125620","article-title":"Placenta: the forgotten organ","volume":"31","author":"Maltepe","year":"2015","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2021042609080970100_DEV146100C29","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.mce.2012.02.009","article-title":"Differential placental expression profile of human Growth Hormone\/Chorionic Somatomammotropin genes in pregnancies with pre-eclampsia and gestational diabetes mellitus","volume":"355","author":"M\u00e4nnik","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"2021042609080970100_DEV146100C30","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1210\/endo-109-4-1150","article-title":"Localization of renin in trophoblasts in human chorion laeve at term pregnancy","volume":"109","author":"Poisner","year":"1981","journal-title":"Endocrinology"},{"key":"2021042609080970100_DEV146100C31","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1126\/science.1111726","article-title":"Latest advances in understanding preeclampsia","volume":"308","author":"Redman","year":"2005","journal-title":"Science"},{"key":"2021042609080970100_DEV146100C32","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1126\/science.1217141","article-title":"GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals","volume":"336","author":"Shenoy","year":"2012","journal-title":"Science"},{"key":"2021042609080970100_DEV146100C33","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1038\/2171152a0","article-title":"Production of renin by in vitro cultures of human chorion and uterine muscle","volume":"217","author":"Symonds","year":"1968","journal-title":"Nature"},{"key":"2021042609080970100_DEV146100C34","doi-asserted-by":"publisher","first-page":"4239","DOI":"10.1073\/pnas.070371497","article-title":"Cardiac fibrosis in mice lacking brain natriuretic peptide","volume":"97","author":"Tamura","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042609080970100_DEV146100C35","doi-asserted-by":"publisher","first-page":"12077","DOI":"10.1038\/ncomms12077","article-title":"Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins","volume":"7","author":"Tyrkalska","year":"2016","journal-title":"Nat. Commun."},{"key":"2021042609080970100_DEV146100C36","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/0143-4004(89)90053-2","article-title":"Vacuolated cytotrophoblast: a subpopulation of trophoblast in the chorion laeve","volume":"10","author":"Yeh","year":"1989","journal-title":"Placenta"},{"key":"2021042609080970100_DEV146100C37","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0014-5793(02)02870-3","article-title":"Overexpression of human metallothionein-III prevents hydrogen peroxide-induced oxidative stress in human fibroblasts","volume":"521","author":"You","year":"2002","journal-title":"FEBS Lett."},{"key":"2021042609080970100_DEV146100C38","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.bbrc.2006.01.042","article-title":"Contribution of inducible nitric oxide synthase and cyclooxygenase-2 to apoptosis induction in smooth chorion trophoblast cells of human fetal membrane tissues","volume":"341","author":"Yuan","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021042609080970100_DEV146100C39","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.lfs.2007.12.016","article-title":"Imbalance between ROS production and elimination results in apoptosis induction in primary smooth chorion trophoblast cells prepared from human fetal membrane tissues","volume":"82","author":"Yuan","year":"2008","journal-title":"Life Sci."},{"key":"2021042609080970100_DEV146100C40","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/j.biocel.2008.09.031","article-title":"Direct contribution of inducible nitric oxide synthase expression to apoptosis induction in primary smooth chorion trophoblast cells of human fetal membrane tissues","volume":"41","author":"Yuan","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2021042609080970100_DEV146100C41","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1172\/JCI116316","article-title":"Preeclampsia is associated with abnormal expression of adhesion molecules by invasive cytotrophoblasts","volume":"91","author":"Zhou","year":"1993","journal-title":"J. Clin. Invest."},{"key":"2021042609080970100_DEV146100C42","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1172\/JCI119388","article-title":"Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome?","volume":"99","author":"Zhou","year":"1997","journal-title":"J. Clin. Invest."},{"key":"2021042609080970100_DEV146100C43","doi-asserted-by":"publisher","first-page":"2862","DOI":"10.1172\/JCI66966","article-title":"Reversal of gene dysregulation in cultured cytotrophoblasts reveals possible causes of preeclampsia","volume":"123","author":"Zhou","year":"2013","journal-title":"J. Clin. Invest."}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dev.146100","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/144\/5\/767\/1850617\/dev146100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.146100\/2053290\/dev_146100v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.146100\/2053290\/dev_146100v1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T17:02:46Z","timestamp":1621357366000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/doi\/10.1242\/dev.146100\/264298\/Severe-preeclampsia-is-associated-with-alterations"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,1]]},"references-count":43,"URL":"https:\/\/doi.org\/10.1242\/dev.146100","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2017,1,1]]},"article-number":"dev.146100"}}