Abstract
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.
Highlights
Fetal growth restriction (FGR) known as intrauterine growth restriction (IUGR), refers to newborns failing to reach their genetically predetermined growth potential (Battaglia and Lubchenco, 1967; Beune et al, 2018; ACOG, 2019)
The mean birth weight of the control group was 6.419 g, standard deviation 0.436 g and the cut-off for FGR was set at 5.547 g as described previously
The newborns of the food restricted group were divided into two further groups, namely FGR and non-FGR according to their birth weight
Summary
Fetal growth restriction (FGR) known as intrauterine growth restriction (IUGR), refers to newborns failing to reach their genetically predetermined growth potential (Battaglia and Lubchenco, 1967; Beune et al, 2018; ACOG, 2019). According to the “thrifty phenotype” hypothesis, when a mother is nutritionally restricted, the in utero modifications that secure fetal energy sufficiency are in priority Even though these adaptive changes have a major impact for short-term survival of the fetus, they tend to make it more susceptible to disease in the future (Hales and Barker, 2001). Evidence shows that FGR has been associated with obesity and the metabolic syndrome and increases the risk for diabetes type-2 and cardiovascular disease later in life (Pervanidou et al, 2006; Pedroso et al, 2017) These FGR-evoked alterations affect both males and females, with females favoring an earlier obesity development in comparison with males (Pedroso et al, 2019). 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
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