Intrauterine growth restriction alters essential fatty acid ratios and essential fatty acid conversion enzymes in a sex-specific manner in the rat

Intrauterine growth restriction (IUGR) increases the risk of chronic lung disease (CLD), and males have worse outcomes. Altered ratios of omega-6 and omega-3 essential fatty acids (EFA) in preterm infants are associated with increased risk of CLD. Conversion of omega-6 and omega-3 EFAs require the same set of EFA conversion enzymes. We hypothesized that IUGR would alter EFA ratios and EFA conversion enzymes in a sex-specific manner in fetal serum, liver and lung. Because maternal docosahexanoic acid (DHA) supplementation has been shown to ameliorate lung dysfunction in IUGR rats, we further hypothesized that alterations in EFA ratios and EFA conversion enzymes would be ameliorated with maternal DHA supplementation. We found that IUGR altered EFA ratios and EFA conversion enzymes in a sex-specific manner. IUGR induced changes in male circulating EFAs that correlate with EFA ratios seen in male preterm infants at increased risk for CLD. Maternal DHA supplementation ameliorated the altered circulating EFAs in male IUGR rats. IUGR induced changes in liver and lung EFA conversion enzyme mRNA and protein did not explain alterations in circulating and lung EFA ratios. We conclude that IUGR induces sex-specific changes in circulating EFA ratios and liver EFA conversion enzymes in newborn IUGR rat pups. We speculate that IUGR induced changes in EFA levels may occur as a result of alterations in placental EFA transfer, and that IUGR impacts placental transfer of EFAs in a sex-specific manner.