Adaptive responses to maternal nutrient restriction alter placental transport in ewes

Maternal nutrient partitioning, uteroplacental blood flow, transporter activity, and fetoplacental metabolism mediate nutrient delivery to the fetus. Inadequate availability or delivery of nutrients results in intrauterine growth restriction (IUGR), a leading cause of neonatal morbidity and mortality. Maternal nutrient restriction can result in IUGR, but only in an unforeseeable subset of individuals. To elucidate potential mechanisms regulating fetal nutrient availability, singleton sheep pregnancies were generated by embryo transfer. Pregnant ewes received either a 50% NRC (NR; n = 24) or 100% NRC (n = 7) diet from gestational Day 35 until necropsy on Day 125. Maternal weight did not correlate with fetal weight; therefore, the six heaviest (NR Non-IUGR) and five lightest (NR IUGR) fetuses from nutrient-restricted ewes, and seven 100% NRC fetuses, were compared to investigate differences in nutrient availability. Insulin, multiple amino acids, and their metabolites, were reduced in fetal circulation of NR IUGR compared to NR Non-IUGR and 100% NRC pregnancies. In contrast, glucose in fetal fluids was not different between groups. There was a nearly two-fold reduction in placentome volume and fetal/maternal interface length in NR IUGR compared to NR Non-IUGR and 100% NRC pregnancies. Changes in amino acid concentrations were associated with altered expression of cationic (SLC7A2, SLC7A6, and SLC7A7) and large neutral (SLC38A2) amino acid transporters in placentomes. Results establish a novel approach to study placental adaptation to maternal undernutrition in sheep and support the hypothesis that amino acids and polyamines are critical mediators of placental and fetal growth in sheep. •Only a subset of nutrient restricted fetuses have fetal weights lower than control fetuses.•Insulin and select amino acids were reduced in circulation of nutrient restricted IUGR fetuses.•Placental amino acid transporter mRNA expression changes are associated with amino acid levels.