title: Unique trophoblast stem cell- and pluripotency marker staining patterns depending on gestational age and placenta-associated pregnancy complications.
abstract: Preeclampsia (PE) and intrauterine growth retardation (IUGR) are rare but severe pregnancy complications that are associated with placental insufficiency often resulting in premature birth. The clinical pathologies are related to gross placental pathologies and trophoblastic deficiencies that might derive from inflammatory processes and oxidative stress injury. The mesenchymal core of placental villi has been identified as a possible niche for trophoblast progenitor cells that are called upon to replenish the injured syncytiotrophoblast layer. These progenitor cells are known to express trophoblast stem cell (CDX2) and pluripotency (SOX2, NANOG and OCT4A) markers, however only little data is available characterizing the expression of these transcription factors beyond the blastocyst stage. We aimed to describe the expression of these factors in healthy 1st and 3rd trimester placentae as well as PE, IUGR and combined PE+IUGR placentae. We analyzed 8 respective samples derived from 1st trimester (elective abortions), and 3rd trimester (healthy controls, PE, IUGR and combined PE+IUGR). We accomplished immunoperoxidase staining to detect the stem cell markers: CDX2 (trophectoderm), SOX2, NANOG and OCT4A (embryonal). Immunoreative scoring was used for objective analyses of staining patterns. All markers display clearly elevated signals in 1st trimester villous samples as compared to healthy 3rd trimester counterparts. Especially CDX2 and NANOG were specific to the cytotrophoblast layer and the mesenchymal core. Specific and differential expression patterns were visible in the villous/extravillous compartment of each placenta-associated pregnancy complication (PE: pan elevated expression; IUGR elevated SOX2 in basal plate; combined PE+IUGR pan loss of expression). Reduction of stem cell transcription factor expression in term placentae indicates temporal regulation, and probably a specific function which is yet to be elucidated. The differential expression patterns within placentae complicated with placenta-associated pregnancy complications indicate that PE, IUGR and combined PE+IUGR are separate entities. It is unclear whether the alterations are the cause or the effect of the clinical pathology.
authors.affiliation: a Department of Obstetrics , Placenta Lab, University Hospital Jena , Jena , Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Weber
authors.affiliation: a Department of Obstetrics , Placenta Lab, University Hospital Jena , Jena , Germany.|b Department of Obstetrics and Gynecology , University Medical Center Groningen, University of Groningen , Groningen , The Netherlands.
authors.forename: Claudia
authors.initials: C
authors.lastname: Göhner
authors.affiliation: c Biomedical Research Center, School of Medicine, Universidad de Valparaiso , Chile.
authors.forename: Sebastian
authors.initials: S
authors.lastname: San Martin
authors.affiliation: d Department of Obstetrics and Gynecology , Ludwig Maximilians University of Munich , Munich , Germany.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Vattai
authors.affiliation: d Department of Obstetrics and Gynecology , Ludwig Maximilians University of Munich , Munich , Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hutter
authors.affiliation: c Biomedical Research Center, School of Medicine, Universidad de Valparaiso , Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Parraga
authors.affiliation: d Department of Obstetrics and Gynecology , Ludwig Maximilians University of Munich , Munich , Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
authors.affiliation: a Department of Obstetrics , Placenta Lab, University Hospital Jena , Jena , Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Schleussner
authors.affiliation: a Department of Obstetrics , Placenta Lab, University Hospital Jena , Jena , Germany.
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.affiliation: a Department of Obstetrics , Placenta Lab, University Hospital Jena , Jena , Germany.|e Praxisklinik am Anger, Kinderwunschzentrum Erfurt , Erfurt , Germany.
authors.forename: Justine S
authors.initials: JS
authors.lastname: Fitzgerald
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000473:pathology; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism* / Q000473:pathology; D011263:Pregnancy Trimester, Third / Q000378:metabolism; D013194:Staining and Labeling; D014327:Trophoblasts / Q000473:pathology*
chemical_list: D015415:Biomarkers
keywords: IUGR; placenta; pluripotency markers; preeclampsia; trophoblast stem cell markers