Consequences of Maternal Nutrient Restriction on Ovine Placental Development
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Maternal nutrient intake and partitioning, uteroplacental blood flow, nutrient transporter activity, and fetoplacental metabolism mediate nutrient delivery to the fetus. Inadequate delivery of nutrients results in intrauterine growth restriction (IUGR), a leading cause of neonatal morbidity and mortality. The present studies exploited natural population variance in nutrient-restricted (NR) ewes to identify subpopulations of IUGR and non-IUGR fetuses as subjects for research to elucidate adaptive mechanisms of fetal-placental development. Singleton pregnancies were generated by embryo transfer and assigned to receive either 50% (n=24) or 100% (n=7) of the National Research Council’s (NRC) recommended dietary intake from Day 35 to Day 125 of gestation, at which time ewes were necropsied. Maternal weight did not correlate with fetal weight; therefore, differences in development of the six heaviest (NR non-IUGR) and six lightest (NR IUGR) fetuses from NR ewes, as well as the seven fetuses from control ewes were compared. Mean weights of NR IUGR fetuses (2.8±0.1 kg) were lower (P<0.05) than for control (4.0±0.1 kg) and NR non-IUGR (4.1±0.1 kg) fetuses. The first study investigated potential mechanisms regulating nutrient availability for fetuses. Results indicated that normal fetal growth in a subpopulation of NR ewes is associated with enhanced delivery of a number of amino acids and their metabolites into the fetal circulation, which may at least partially result from up-regulation of expression of amino acid transporter mRNAs in the placentome. The second study elucidated potential physiological mechanisms regulating placental growth and development in ewes having NR IUGR and NR non-IUGR fetuses. Results suggest that placentome morphology and angiogenic growth factor expression varies in response to maternal nutritional challenge during pregnancy and may play critical roles in regulating fetal growth. The third study was conducted to capitalize on natural population variance in NR ewes to identify novel factors regulating placental growth and function. Results suggest that enhanced fetal growth in NR non-IUGR pregnancies is associated with an altered expression of genes related to immune response and function in the placentome. Collectively, results of these studies suggest that enhanced fetal growth in a subset of NR ewes is associated with enhanced expression of select nutrient transporters and angiogenic factors, increased nutrient availability to the fetus, altered placentome morphology, and an altered immune response within the placentomes of those ewes.
Keith, Ashley Brooke (2015). Consequences of Maternal Nutrient Restriction on Ovine Placental Development. Doctoral dissertation, Texas A & M University. Available electronically from