Dataset Information

Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition.

ABSTRACT:

Background

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. In this study, we investigated the result of maternal food restriction on liver protein expression in Wistar male newborn pups.

Materials & methods

Ten (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.

Results

In 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.

Conclusion

This 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.

SUBMITTER: Sarli PM

PROVIDER: S-EPMC8195994 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFetal growth restriction (FGR) has been associated with a higher risk of developing adverse perinatal outcomes and distinct neurodevelopmental and neurobehavioral disorders. The aim of the present study was to investigate the impact of prenatal food restriction on the brain proteome in both FGR and appropriately grown rats and to identify potential pathways connecting maternal malnutrition with altered brain development.MethodsTen time-dated pregnant Wistar rats were housed individually at their 12th day of gestation. On the 15th day of gestation, the rats were randomly divided into two groups, namely the food restricted one (n = 6) and the control group (n = 4). From days 15 to 21 the control group had unlimited access to food and the food restricted group was given half the amount of food that was on average consumed by the control group, based on measurements taken place the day before. On the 21st day of gestation, all rats delivered spontaneously and after birth all newborn pups of the food restricted group were weighed and matched as appropriately grown (non-FGR) or growth restricted (FGR) and brain tissues were immediately collected. A multiplex experiment was performed analyzing brain tissues from 4 FGR, 4 non-FGR, and 3 control male offspring. Differentially expressed proteins (DEPs) were subjected to bioinformatics analysis in order to identify over-represented processes.ResultsProteomic analysis resulted in the profiling of 3,964 proteins. Gene ontology analysis of the common DEPs using DAVID (https://david.ncifcrf.gov/) showed significant enrichment for terms related to cellular morphology, learning, memory and positive regulation of NF-kappaB signaling. Ingenuity Pathway Analysis showed significant induction of inflammation in FGR pups, whereas significant induction of cell migration and cell spreading were observed in non-FGR pups.ConclusionThis study demonstrated that in both FGR and non-FGR neonates, a range of adaptive neurodevelopmental processes takes place, which may result in altered cellular morphology, chronic stress, poor memory and learning outcomes. Furthermore, this study highlighted that not only FGR, but also appropriately grown pups, which have been exposed to prenatal food deprivation may be at increased risk for impaired cognitive and developmental outcomes.