Influence of maternal nutrition on placental vascularity and mRNA expression of angiogenic factors (AFs) and their receptors (AFRs) in adolescent sheep.

Placental and fetal growth are compromised in rapidly growing adolescent ewes. Our aim was to determine the ontogeny of placental AF/AFR mRNA expression and vascular morphology throughout gestation. Singleton pregnancies (single sire) were established by embryo transfer and then adolescent dams were offered a high (H, n=30) or control (C, n=34) nutrient intake. Whole placentomes, collected at Day (D) 50, 90 or 130 of gestation, were (a) frozen for quantitative real-time RT-PCR determination of placental AF/AFR mRNA expression or (b) perfusion-fixed and stained for quantification of vascular morphology. Placentome mass was independent of nutrition at D50 and 90, and by D130 both placentome (- 46%) and fetal weight (-20%) were reduced in H pregnancies. Placentome mRNA expression of vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and Ang-2, basic fibroblast growth factor (FGF-2), endothelial nitric oxide synthase (eNOS), and placental growth factor (PLGF), and AFRs VEGFR-1 (flt), VEGFR-2 (KDR), and FGFR-2 increased as gestation advanced (P<0.001), whereas, hypoxia inducible factor (HIF1α), soluble guanylate cyclase (NO receptor) and neuropilin (NP)-2) declined (P<0.05). H-intakes reduced NP-1 expression (P<0.04) at each stage and increased eNOS at D130 (P<0.01). Tie-2 (Ang receptor) expression was unaffected by stage or nutrition level. H-intakes reduced (P<0.004) capillary area density and size in the cotyledon at D50, but thereafter placental vascular morphology per unit tissue was largely unaffected. Similarly, caruncular vascular morphology was independent of nutrition throughout. This study provides clues as to the AF/AFR's involved in the nutritional mediation of placental growth. As vascular morphology per unit placenta is largely unperturbed at D90 and 130, the data further suggest that it is the small size of the placenta and thus the reduction in total vascular volume that is the major limitation to fetal nutrient supply in late pregnancy. [ABSTRACT FROM AUTHOR]