Abstract
BackgroundFetal growth restriction (FGR) has been associated with adverse perinatal outcomes and epigenetic modifications that impact gene expression leading to permanent changes of fetal metabolic pathways and thereby influence development of disease in childhood and adult life. In this study, we investigated the result of maternal food restriction on liver protein expression in Wistar male newborn pups.Materials & MethodsTen (n = 10) timed pregnant Wistar rats on their 14th day of gestation were randomly assigned to either control (n = 4) or food restricted group (n = 6). The control group had ad libitum access to food. In the food restricted group, maternal diet was limited in a moderate fashion (50%) from day 15 of pregnancy until delivery. All rats delivered spontaneously on day 21 and newborn pups were immediately weighed. Pups born to normally nourished mothers were considered as controls, while pups born to food restricted mothers were subdivided into two groups, based on their birth weight: growth restricted (FGR) and appropriately grown (non-FGR). Rats were euthanized immediately after birth and liver tissues of 11 randomly selected male offspring (FGR n = 4, non-FGR n = 4, control n = 3) were collected and analyzed using quantitative proteomics.ResultsIn total 6,665 proteins were profiled. Of these, 451 and 751 were differentially expressed in FGR and non-FGR vs. control, respectively, whereas 229 proteins were commonly expressed. Bioinformatics analysis of the differentially expressed proteins (DEPs) in FGR vs. control revealed induction of the super-pathway of cholesterol biosynthesis and inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway. Analysis of DEPs in non-FGR vs. control groups showed inhibition of thyroid hormone metabolism, fatty acid beta oxidation, and apelin liver signaling pathway.ConclusionThis study demonstrates the impact of prenatal food restriction on the proteomic liver profile of FGR and non-FGR offspring underlying the importance of both prenatal adversities and birth weight on liver-dependent postnatal disease.
Highlights
Fetal Growth Restriction (FGR) refers to a fetus that has failed to achieve its biological growth potential due to pathological conditions such as maternal/fetal disease and placental dysfunction
Newborn pups delivered by starved mothers, were further divided to Fetal Growth Restricted (FGR) group when birthweight was < - 2SDs of the mean BW of the control offspring and non-FGR group when birthweight was > - 2SDs of the mean BW of the control
Bioinformatics analysis of differentially expressed proteins (DEPs) in FGR compared to control groups using Ingenuity Pathway Analysis (IPA) showed: a. induction of the super pathway of cholesterol biosynthesis (z = 2.2; p = 1.5e-4) (Figure 4), and b. inhibition of thyroid hormone metabolism (Figure 5) (z = −2.0; p = 4.6e-3), fatty acid beta oxidation (z = −2.0; p = 2.7e-3) (Figure 6), and apelin liver signaling pathway (Figure 7) (z = −2.2; p = 8.5e-5)
Summary
Fetal Growth Restriction (FGR) refers to a fetus that has failed to achieve its biological growth potential due to pathological conditions such as maternal/fetal disease and placental dysfunction. According to Barker’s hypothesis, an unfavorable intrauterine environment may have negative long-term effects in adult life [3]. According to the thrifty phenotype hypothesis [4], FGR impairs the growth of organs such as the liver in order to maintain homeostasis of other crucial for survival organs and systems. These metabolic adaptations, enable fetuses to survive in a malnourished intrauterine environment. Fetal growth restriction (FGR) has been associated with adverse perinatal outcomes and epigenetic modifications that impact gene expression leading to permanent changes of fetal metabolic pathways and thereby influence development of disease in childhood and adult life. We investigated the result of maternal food restriction on liver protein expression in Wistar male newborn pups
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
