Characterisation of the syncytiotrophoblast glycocalyx across gestation and in fetal growth restriction (#509)
Background: Fetal growth restriction (FGR) occurs when fetal growth decelerates because placental exchange capacity cannot keep up with fetal demand. The glycocalyx is a carbohydrate layer lining the endothelial cell surface in blood vessels, where it has important roles in facilitating mechanosensation and exchange. In pathologies such as sepsis, and cardiovascular disease, the glycocalyx is thinner, with increased shedding into the circulation. On the surface of the placenta, the syncytiotrophoblast is also covered in a glycocalyx layer. However, changes to this layer throughout pregnancy and in pathologies such as FGR are not well understood. This study thus aimed to quantify the thickness and coverage of the syncytiotrophoblast glycocalyx across gestation and in FGR
Methods: Villous tissue samples from first trimester (n=10), normal (n=5) or FGR (n=5) placentae were stained with an Alcian Blue protocol, resin embedded, and imaged by transmission electron microscopy. Glycocalyx thickness and coverage on syncytiotrophoblast microvilli was quantified using custom MATLAB code.
Results: Within the first trimester, glycocalyx thickness and coverage increased significantly from 7-8 weeks (8.31±0.41nm thick, 99.15%±0.10% coverage) to 10-13 weeks of gestation (11.19±0.49nm thick (p<0.0001), 99.38%±0.08% coverage (p=0.0344)), potentially reflecting changes associated with the onset of maternal blood flow to the intervillous space. This trend continued throughout gestation, with glycocalyx thickness and coverage increasing from the first trimester (10.20±0.32nm thick, 99.26%±0.06% coverage) to the third trimester (15.94±0.87nm thick, 99.62%±0.06% coverage, p<0.0001 for both). Compared to normal term placentae, in FGR glycocalyx thickness was decreased (7.59±0.29nm, p<0.0001), but coverage was not altered.
Conclusion: The thinner glycocalyx in FGR could indicate potential damage to this layer, potentially contributing to impaired placental function by impacting coagulation or syncytiotrophoblast permeability. Further understanding of the molecular signatures associated with increased glycocalyx shedding in FGR may enable identification of early serum biomarkers to better identify at-risk babies.