| Description |
Intrauterine growth restriction (IUGR) refers to failure of the fetus to achieve its genetic growth potential in utero and is commonly caused by uteroplacental insufficiency secondary to maternal hypertensive disorders. A hallmark of IUGR is a decrease in circulating docosahexaenoic acid (DHA), an ω-3 fatty acid essential for organogenesis and favorable neonatal outcomes. Human and animal models demonstrate that IUGR causes a general predisposition to hepatic dysfunction and steatosis, both precursors of nonalcoholic fatty liver disease (NAFLD). However, previous clinical trials examining the effects of perinatal DHA supplementation in preterm and term infants have shown sexdivergent outcomes for growth and adiposity. Our preliminary data demonstrate that IUGR increases lipid accumulation in the liver of day 21 male IUGR rat pups, and this accumulation is normalized with DHA supplementation. Despite the prevalence of hepatic steatosis in IUGR, contributing mechanisms are unknown, as are the effects of DHA supplementation in the context of IUGR. We hypothesized that IUGR would cause sexdivergent alterations in hepatic PEMT, histone methylation, and expression of downstream hepatic lipid protein products, and that DHA supplementation would normalize observed molecular changes. With our IUGR rat model, we measured mRNA transcript levels using real-time RT PCR and protein abundance using Western blot. Mediators of hepatic lipid accumulation were minimally affected by IUGR, but the presence of supplemental DHA resulted in multiple sex-divergent changes in the expression of molecular mediators of lipid clearance, with and without IUGR. Subsequent studies will examine the cause-and-effect relationship between these mediators, mechanisms of sex-divergent responses, and earlier timepoints that may correspond to peak molecular changes in the IUGR phenotype. |
