Fetal growth restriction (FGR) or small for gestational age (SGA), when a baby fails to reach its predestined genetic growth capacity, is a leading cause of stillbirth. The molecular pathogenesis of SGA is poorly understood and there are no accurate biomarkers.
We have recently identified Syndecan-1, a cell surface proteoglycan, as significantly reduced in the circulation of women preceding their diagnosis of SGA. In addition, we’ve shown that placental Syndecan-1 is reduced by hypoxia and its knockdown impairs trophoblast proliferation.
The aim of this study was to characterise Syndecan-1 in the placentas and blood of women with established FGR. In addition, we sought to determine how sydnecan-1 is released from placenta and whether silencing syndecan-1 altered the expression of Placental Growth Factor, a molecule reduced in SGA and important in normal placental function.
In a cohort of placentas collected from women who delivered a FGR baby at <34 weeks’ gestation (n= 18), Syndecan-1 mRNA expression was significantly increased relative to preterm control placentas (n=15), whilst circulating Syndecan-1 protein was significantly reduced in the FGR cohort (n=9) relative to controls (n=17). Treatment of isolated primary human trophoblast (n=4 separate isolations) with broad spectrum matrix metalloproteinase inhibitor batimistat potently reduced the secretion of Syndecan-1 in a dose-dependent manner without altering mRNA expression. siRNA knockdown of Syndecan-1 in primary trophoblast however did not alter the mRNA expression of Placental Growth Factor.
In conclusion, Syndecan-1 is reduced in the circulation of women with both established FGR and preceding diagnosis of FGR/SGA whilst placental mRNA expression is increased in FGR. We provide new evidence that members of the matrix metalloproteinase family are likely regulators of placental Syndecan-1 secretion.