title: Placental expression of heparan sulfate 3-O-sulfotransferase-3A1 in normotensive and pre-eclamptic pregnancies.
abstract: BACKGROUND
  The endothelial glycocalyx, consisting of membrane-bound proteoglycans and attached glycosaminoglycans plays an important role in vascular homeostasis. We aimed to assess whether glycocalyx mRNA transcripts are differentially expressed in placental tissue of pre-eclamptic and normotensive women.
  
  
  METHODS
  We evaluated the expression of transcripts encoding for proteins involved in glycocalyx synthesis and degradation using a microarray analysis of placental mRNA obtained from pre-eclamptic and normotensive women. Participants were recruited from the department of obstetrics at a university hospital in Amsterdam, The Netherlands. The most prominent differentially expressed transcript was validated by qPCR on 112 additional placenta samples.
  
  
  RESULTS
  Of 78 preselected genes involved in glycocalyx synthesis and degradation, only HS3ST3A1 mRNA was differentially expressed in placental tissue obtained from pre-eclamptic women (N = 12) compared to normotensive women (N = 12, fold change = 0.61, p = 0.02). Validation with qPCR in additional placental samples of 64 normotensive and 48 pre-eclamptic women confirmed that normalized mRNA expression of HS3ST3A1 was decreased by 27% (95% CI 14%-41%) in placental tissue obtained from pre-eclamptic compared to normotensive women (p < 0.001). HS3ST3A1 expression was positively correlated with neonatal birth weight in normotensive women (r = 0.35, p < 0.01) and inversely correlated with mean arterial pressure of women with pre-eclampsia (r = 0.32, p = 0.02).
  
  
  CONCLUSIONS
  The mRNA expression of HS3ST3A1, which encodes for a 3-O sulfating enzyme of heparan sulfate (3-OST-3A1), is decreased in pre-eclamptic placental tissue. Expression of this glycocalyx synthesis transcript is correlated with maternal blood pressure and neonatal birth weight, suggesting a possible role in pre-eclampsia-associated placental dysfunction.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: f.amraoui@amc.nl.
authors.forename: F
authors.initials: F
authors.lastname: Amraoui
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands; Reproductive Biology Laboratory, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: h.hassanilahsinoui@amc.nl.
authors.forename: H
authors.initials: H
authors.lastname: Hassani Lahsinoui
authors.affiliation: Reproductive Biology Laboratory, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: s.boussata@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Boussata
authors.affiliation: Reproductive Biology Laboratory, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: r.keijser@amc.nl.
authors.forename: R
authors.initials: R
authors.lastname: Keijser
authors.affiliation: Reproductive Biology Laboratory, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: g.j.veenboer@amc.nl.
authors.forename: G J M
authors.initials: GJ
authors.lastname: Veenboer
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: s.middeldorp@amc.nl.
authors.forename: S
authors.initials: S
authors.lastname: Middeldorp
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: j.a.vanderpost@amc.nl.
authors.forename: J A M
authors.initials: JA
authors.lastname: van der Post
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands; Reproductive Biology Laboratory, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: c.ris@amc.nl.
authors.forename: C
authors.initials: C
authors.lastname: Ris-Stalpers
authors.affiliation: Reproductive Biology Laboratory, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: g.b.afink@amc.nl.
authors.forename: G B
authors.initials: GB
authors.lastname: Afink
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: b.j.vandenborn@amc.nl.
authors.forename: B J H
authors.initials: BJ
authors.lastname: van den Born
mesh_terms: D000328:Adult; D001724:Birth Weight; D001794:Blood Pressure; D016022:Case-Control Studies; D005260:Female; D019276:Glycocalyx / Q000378:metabolism*; D054794:Glycomics; D006801:Humans; D017403:In Situ Hybridization; D046228:Microarray Analysis; D010920:Placenta / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000201:enzymology*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D015238:Sulfotransferases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015238:Sulfotransferases; C000610627:HS3ST3A1 protein, human; C021350:heparitin sulfotransferase
keywords: 3-O-Sulfotransferase-3A1; Birth weight; Blood pressure; Glycocalyx; Heparan sulfate; Pre-eclampsia