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

• Published in: Placenta (Eastbourne) Vol. 36; no. 11; pp. 1218 - 1224
• Main Authors: Amraoui, F, Hassani Lahsinoui, H, Boussata, S, Keijser, R, Veenboer, G.J.M, Middeldorp, S, van der Post, J.A.M, Ris-Stalpers, C, Afink, G.B, van den Born, B.J.H
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-11-2015
• Subjects: 3-O-Sulfotransferase-3A1; Adult; Birth Weight; Blood Pressure; Case-Control Studies; Female; Glycocalyx; Glycocalyx - metabolism; Glycomics; Heparan sulfate; Humans; In Situ Hybridization; Internal Medicine; Microarray Analysis; Obstetrics and Gynecology; Placenta - enzymology; Pre-eclampsia; Pre-Eclampsia - enzymology; Pregnancy; Real-Time Polymerase Chain Reaction; Sulfotransferases - metabolism; Young Adult; Heparan sulfate; Glycocalyx; Blood pressure; Birth weight; Pre-eclampsia; 3-O-Sulfotransferase-3A1
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2015.09.008

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.