Placental expression of heparan sulfate 3-O-sulfotransferase-3A1 in normotensive and pre-eclamptic pregnancies

Placenta. 2015 Nov;36(11):1218-24. doi: 10.1016/j.placenta.2015.09.008. Epub 2015 Sep 16.

Abstract

Introduction: 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.

Keywords: 3-O-Sulfotransferase-3A1; Birth weight; Blood pressure; Glycocalyx; Heparan sulfate; Pre-eclampsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Birth Weight*
  • Blood Pressure
  • Case-Control Studies
  • Female
  • Glycocalyx / metabolism*
  • Glycomics
  • Humans
  • In Situ Hybridization
  • Microarray Analysis
  • Placenta / enzymology*
  • Pre-Eclampsia / enzymology*
  • Pregnancy
  • Real-Time Polymerase Chain Reaction
  • Sulfotransferases / metabolism*
  • Young Adult

Substances

  • Sulfotransferases
  • HS3ST3A1 protein, human
  • heparitin sulfotransferase