Introduction
Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. Idiopathic FGR pregnancies are associated with abnormal umbilical artery Doppler velocimetry and histological evidence of placental thrombosis. Heparan sulphate containing proteoglycans (HSPG), which interacts with antithrombin are highly expressed in the placenta. This interaction may prevent thrombosis within the placental circulation. Glypicans (GPC) are a family of HSPGs. We hypothesised that altered expression of the HSPGs, GPC-1 and GPC-3, may result in dysregulation of placental thrombosis, and therefore contribute to the development of FGR. The aim of this study was to determine the expression of GPC-1 and GPC-3 in FGR-affected placentae compared with gestation-matched controls.
Methods
Placental RNA was obtained from 24 FGR and 24 control placentae and reverse transcribed into cDNA. Real-time PCR was used to determine the mRNA expression of GPC-1 and GPC-3, relative to the housekeeping gene, GAPDH, according to the 2-ΔΔCT method [1]. Western immunoblotting and immunohistochemistry were performed to determine the protein expression and cellular localisation of GPC-1 and GPC-3, respectively. Data are represented as mean±SD with statistical analysis by Mann-Whitney U test.
Results
The table shows the relative mean mRNA expression of GPC-1 and GPC-3 in FGR-affected placentae compared with gestation-matched controls.
|
Mean mRNA expression (mean±SEM) |
|
||
|
Glypican |
Control |
FGR |
P Value |
|
GPC-1 |
1.01±0.31 |
0.68±0.32 |
0.003 |
|
GPC-3 |
2.19±1.40 |
1.31±0.56 |
0.02 |
Conclusion
Reduced expression of GPC-1 and GPC-3 in the FGR placentae may contribute to dysregulated placental thrombosis in FGR. Further investigation fn the functional role of GPC may provide novel insight to understanding the molecular mechanisms of FGR.