Lipid metabolism is altered in maternal, placental, and fetal tissues of ewes with small for gestational age fetuses†

Nutrient restriction (NR) has the potential to negatively impact birthweight, an indicator of neonatal survival and lifelong health. Those fetuses are termed as small for gestational age (SGA). Interestingly, there is a spectral phenotype of fetal growth rates in response to NR associated with changes in placental development, nutrient and waste transport, and lipid metabolism. A sheep model with a maternal diet, starting at Day 35, of 100% National Research Council (NRC) nutrient requirements (n= 8) or 50% NRC (n= 28) was used to assess alterations in fetuses designated NR SGA (n= 7) or NR NonSGA (n= 7) based on fetal weight at Day 135 of pregnancy. Allantoic fluid concentrations of triglycerides were greater in NR SGA fetuses than 100% NRC and NR NonSGA fetuses at Day 70 (P< 0.05). There was a negative correlation between allantoic fluid concentrations of triglycerides (R2= 0.207) and bile acids (R2= 0.179) on Day 70 and fetal weight at Day 135 for NR ewes (P< 0.05). Bile acids were more abundant in maternal and fetal blood for NR SGA compared to 100% NRC and NR NonSGA ewes (P< 0.05). Maternal blood concentrations of NEFAs increased in late pregnancy in NR NonSGA compared to NR SGA ewes (P< 0.05). Protein expression of fatty acid transporter SLC27A6 localized to placentomal maternal and fetal epithelia and decreased in Day 70 NR SGA compared to 100% NRC and NR NonSGA placentomes (P< 0.05). These results identify novel factors associated with an ability of placentae and fetuses in NR NonSGA ewes to adapt to, and overcome, nutritional hardship during pregnancy.Summary Sentence Allantoic fluid concentrations of triglycerides and bile acids from nutrient restricted ewes at mid-gestation are negatively correlated with fetal weights near term, while placental fatty acid transporter SLC27A6 protein is reduced in small for gestational age fetuses.