Placentae from pregnancies with fetal growth restriction (FGR) exhibit poor oxygen and nutrient exchange, in part due to impaired placental vascular development. pMSCs reside in a perivascular niche, where they may influence blood vessel formation and function. However, the role of pMSCs in influencing vascular dysfunction in FGR is unknown. To elucidate the mechanisms by which pMSCs may impact placental vascularisation we compared the transcriptomes of pMSCs from normal and FGR pregnancies.
MSCs were isolated from FGR (<5thcentile) (n=9) and gestation-matched control placentae (n=9). Transcriptomes were compared using Affymetrix microarrays. Genes/proteins of interest were validated by qPCR and by immunohistochemistry (IHC).
Whilst at the transcriptome level there were no statistically significant differences between normal and FGR pMSCs, the data were used to generate hypotheses. Several genes linked to vascular function exhibited distinct fold changes, supporting reports that FGR placentae exhibit differences in vascular compliance and structure that may impair blood flow and exchange. qPCR, demonstrated that the expression of Tenascin-X, ADAMTS1 and Fibulin-2 were significantly upregulated, whilst hyaluronan synthase-2 was significantly downregulated, in pMSCs from FGR placentae relative to controls (p<0.05 for all, n= 9 FGR and 9 control placentae). IHC indicated all four proteins were expressed perivascularly in third-trimester placentae.
Tenascin-X and Fibulin-2 maintain vessel elasticity, and their increased expression in FGR pMSCs could help explain the increased distensibility of FGR blood vessels. ADAMTS1 and hyaluronan synthase-2 regulate angiogenesis, and their differential expression by pMSCs from FGR placentae may contribute to the impaired angiogenesis in these placentae. Future work to relate expression of these proteins to vessel compliance in normal and FGR placentae will inform in silico models to better understand normal and abnormal placental haemodynamics and exchange function.