Is human placenta proteoglycan remodeling involved in pre-eclampsia?

Abstract

Impaired placento-fetal communication is a coherent symptom of exaggerated pre-eclampsia. The impact of the cellular expression of different glycosaminoglycans (GAGs) in this event on the placenta in pre-eclampsia is still obscure. This is the first study aimed at discovering the relationship between structural alterations of different sulfated GAGs at the molecular level and the development of pre-eclampsia in inflicted placenta. Sulfated GAGs were isolated and purified from control and pre-eclampsia placentas. The amount and the molecular weight of GAG in each tissue sample were measured. The polydispersity of the recovered GAG samples were determined by polyacrylamide gel electrophoresis. The disaccharide composition of chondroitin sulfate, dermatan sulfate and heparan sulfate were deduced by chondroitinase and heparinase depolymerization followed by liquid chromatography-mass spectrometry. The in vivo sulfo-modulation of GAGs in pre-eclampsia and control placenta were examined using RT-PCR to determine the transcription levels of different sulfotransferases involved in GAG biosynthesis. Marked differences in GAG sulfation patterns and mRNA level of encoding selected GAG O-sulfotransferases were observed in pre-eclampsia. These data suggest a linkage between pre-eclampsia and the observed alterations in placental GAGs and could provide new insights about the modulating role of GAGs in the development and the severity of placental pre-eclampsia.

Fig. 1

PAGE analysis on GAGs isolated from different tissues. Two gels are shown in the upper panels. Lanes (Std) are the heparin oligosaccharide standard. Lanes 1 to 12 are correspondence to GAGs from duplicate (i.e., A1, A2) samples (see Table 2). Lanes (HS) are heparan sulfate control. The lower panels show scanned data from each gel used to calculate the molecular weight of each GAG sample [23]

Fig. 2

Analysis of GAG disaccharides. Ion-pairing chromatography of CS/DS and Hp/HS disaccharides. a 8 disaccharide standards of CS/DS; b disaccharides of CS/DS from one sample (4) of the control group. c disaccharides of CS/DS from a representative sample (11) of the pre-eclampsia group; d 8 disaccharide standards of Hp/HS; e disaccharides of Hp/HS from one sample (4) of the control group. f disaccharides of Hp/HS from a representative (11) of the pre-eclampsia group. g structure and MS/MS of the 6S and UA2S Hp/HS disaccharides