Placental expression of angiogenesis-related genes and their receptors in IUGR pregnancies: correlation with fetoplacental and maternal parameters.

Objectives:Aberrations in placental vascular development compromising fetal supply of oxygen and essential nutrients can be a significant contributor to intrauterine growth restriction (IUGR). The development of placental vascular tree is under the influence of two families of growth factors, namely the vascular endothelial growth factor (VEGF) family and angiopoietin/TEK family. In this study, we have examined the expression of angiogenesis-related growth factors, mainly VEGF family and angiopoietin-TEK (endothelial-specific receptor tyrosine kinase) family genes in placentae from IUGR pregnancies uncomplicated by preeclampsia (PE) compared to normal pregnancies. Methods:Placentae from normotensive IUGR (n = 42) and appropriate for gestational age (AGA) pregnancies (n = 47) were collected and examined histologically. Clinical parameters were obtained from the medical records. Real-time quantitative PCR was performed to assess placental transcript abundance ofVEGF,PGF,FLT1,ANGPT1,ANGPT2, andTEKnormalized to a panel of reference genes. Associations of placental transcript abundance of the genes with maternal, placental, and neonatal parameters were tested. Results:Placental transcript abundance forVEGF(relative expression 10.81 versus 12.98,p< .001),PGF(12.14 versus 13.8,p< .001) andANGPT2(3.67 versus 9.55,p= .002) were significantly lower in IUGR placentae compared to AGA. The transcript level ofVEGFshowed significant negative correlation with birth weight (r= -0.419,p= .006), placental weight (r= -0.318,p= .040), placental length (r= -0.389,p= .011) and breadth (r = -0.308,p= .047) only in the IUGR group. Presence of histopathological features of hypoxia correlated with significantly higher transcript levels ofPGFin IUGR placentae (12.6 versus 10.9,p= .046). Conclusion:The low levels ofVEGFtranscripts may be responsible for the impaired angiogenesis in IUGR placentae. The significance of higher relative expression ofPGFin the presence of chronic hypoxia needs to be explored.