Placental expression of VEGF, PIGF and their receptors in a model of placental insufficiency - Intrauterine growth restriction (PI-IUGR)

Placental development requires adequate and organized interaction of vascular growth factors and their receptors, including vascular endothelial growth factor (VEGF) and placental growth factor (PIGF). Both VEGF and PIGF, acting through the tyrosine kinase receptors VEGFR-1 and VEGFR-2, have been implicated in playing a role in ovine placental vascular-development. The present studies describe the placental expression of components of the VEGF family at two maturational time points (55 and 90 days post coitus, dpc) in a hyperthermic-induced ovine model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Both caruncular and cotyledonary VEGF and PlGF mRNA concentration increased with gestational age (P<0.05), whereas only cotyledonary VEGF and PlGF protein concentration increased over gestation (P<0.002). At 55 dpc, VEGF mRNA concentration was elevated in hyperthermic (HT) ewes, compared to control thermoneutral (TN) animals (TN; 0.52 +/- 0.08 vs HT; 1.27 +/- 0.17 VEGF/GAPDH, P<0.001). At 90 dpc, expression of PIGF and VEGF mRNA was not altered by the HT treatment. Both TN cotyledonary VEGFR-1 and VEGFR-2 mRNA expression levels rose significantly over the period studied (P<0.05 and P<0.01 respectively). Receptor mRNA concentration in HT cotyledonary tissue was significantly reduced at 90 dpc (VEGFR-1; TN 0.21 +/- 0.02 vs HT 0.11 +/- 0.01 VEGFR-1/actin, P<0.05, VEGFR-2; TN 0.18 +/- 0.05 vs HT 0.07 +/- 0.01 VEGFR-2/actin, P<0.01). Soluble VEGFR-1 (sVEGFR-1) mRNA was not detected in these tissues. These alterations in growth factor and growth factor receptor mRNA expression, as a result of environmental heat stress early in placental development, could impair normal placental vascular development. Furthermore, alterations in VEGF, VEGFR-1 and VEGFR-2 mRNA expression, during the period of maximal placental growth, may contribute to the development of placental insufficiency, and ultimately intrauterine growth restriction. (C) 2002 Elsevier Science Ltd.