Influence of Maternal Nutrition on Messenger RNA Expression of Placental Angiogenic Factors and Their Receptors at Midgestation in Adolescent Sheep1

Abstract

Previous studies have shown that placental growth and pregnancy outcome are severely compromised in adolescent ewes overnourished to promote rapid maternal growth. Using this paradigm, the aim of the present study was to investigate expression of the major angiogenic factors and their receptors in the placenta at the onset of the most rapid phase of fetal growth. Singleton pregnancies to a single sire were established by embryo transfer, and thereafter, adolescent dams were offered a high or moderate nutrient intake predicted to induce compromised or normal fetoplacental size at term, respectively. Ovine-specific oligonucleotide probe and primer sets for several angiogenic factors and their receptors were developed for quantitative real-time reverse transcription-polymerase chain reaction determination of placentome mRNA expression at Day 81 of gestation. Total placentome weight and fetal weight were equivalent in high- compared with moderate-intake groups at this stage of gestation. Placentome expression of the angiogenic factors, vascular endothelial growth factor, angiopoietins 1 and 2, and nitric oxide synthase 3, were reduced in overfed ewes. Similarly, level of expression of vascular endothelial growth factor/vascular permeability factor receptor (FLT1) was less in overfed ewes. Thus, in the adolescent, maternal overnutrition has a negative impact on midgestation placental angiogenic factor/ receptor expression. This may impact placental vascularity and explain why uteroplacental mass, blood flow, and nutrient uptake are compromised in late pregnancy, resulting in low-birth-weight offspring.