title: Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion.
abstract: Pre-eclampsia (PE), which affects ∼8% 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 upregulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g. placental proteins, markers of oxidative stress). We confirmed an sPE-related increase in production of PAPPA1, which releases IGF1 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.
authors.affiliation: Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.|Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.|Fundación Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI, INCLIVA, Biomedical Research Institute, Valencia University, Valencia, 46010, Spain.|Fundación Igenomix, Valencia, 46980, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Garrido-Gomez
authors.affiliation: Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.|Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Ona
authors.affiliation: Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.|Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Mirhan
authors.initials: M
authors.lastname: Kapidzic
authors.affiliation: Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.|Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gormley
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI, INCLIVA, Biomedical Research Institute, Valencia University, Valencia, 46010, Spain.|Fundación Igenomix, Valencia, 46980, Spain.|Department of Obstetrics and Gynecology, School of Medicine, Stanford University, CA 94305, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.affiliation: Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.|Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Genbacev
authors.affiliation: Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA sfisher@cgl.ucsf.edu.|Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA.|The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA.|Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Susan J
authors.identifier: 0000-0001-7745-4850
authors.initials: SJ
authors.lastname: Fisher
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D002823:Chorion / Q000166:cytology / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007633:Keratins / Q000378:metabolism; D018384:Oxidative Stress; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D010929:Placentation; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011485:Protein Binding; D014158:Transcription, Genetic; D059467:Transcriptome; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D007633:Keratins; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: Chorion; Cytotrophoblast; Human; PAPPA1; Pre-eclampsia; Preterm birth