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

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 i...

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Main Authors: Polyxeni-Maria Sarli, Antigoni Manousopoulou, Elias Efthymiou, Andreas Zouridis, Anastasios Potiris, Panagiota Pervanidou, Konstantinos Panoulis, Nikolaos Vlahos, Efthymios Deligeoroglou, Spiros D. Garbis, Makarios Eleftheriades
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Endocrinology
Subjects:
FGR
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2021.684220/full
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spelling doaj-9edd3176adfd4a80bdc521349b1529882021-05-28T10:15:48ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-05-011210.3389/fendo.2021.684220684220Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal UndernutritionPolyxeni-Maria Sarli0Antigoni Manousopoulou1Elias Efthymiou2Andreas Zouridis3Anastasios Potiris4Panagiota Pervanidou5Konstantinos Panoulis6Nikolaos Vlahos7Efthymios Deligeoroglou8Spiros D. Garbis9Makarios Eleftheriades10Second Department of Obstetrics and Gynaecology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceBeckman Research Institute, City of Hope National Medical Center, Duarte, CA, United StatesSecond Department of Obstetrics and Gynaecology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceSecond Department of Obstetrics and Gynaecology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceSecond Department of Obstetrics and Gynaecology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Paediatrics, Medical School, National and Kapodistrian University of Athens, Athens, GreeceSecond Department of Obstetrics and Gynaecology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceSecond Department of Obstetrics and Gynaecology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceSecond Department of Obstetrics and Gynaecology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceInstitute for Life Sciences, University of Southampton, Southampton, United KingdomSecond Department of Obstetrics and Gynaecology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceBackgroundFetal 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.https://www.frontiersin.org/articles/10.3389/fendo.2021.684220/fullFGRfetal programmingfood restrictionmetabolic disordersliver proteomics
collection DOAJ
language English
format Article
sources DOAJ
author Polyxeni-Maria Sarli
Antigoni Manousopoulou
Elias Efthymiou
Andreas Zouridis
Anastasios Potiris
Panagiota Pervanidou
Konstantinos Panoulis
Nikolaos Vlahos
Efthymios Deligeoroglou
Spiros D. Garbis
Makarios Eleftheriades
spellingShingle Polyxeni-Maria Sarli
Antigoni Manousopoulou
Elias Efthymiou
Andreas Zouridis
Anastasios Potiris
Panagiota Pervanidou
Konstantinos Panoulis
Nikolaos Vlahos
Efthymios Deligeoroglou
Spiros D. Garbis
Makarios Eleftheriades
Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition
Frontiers in Endocrinology
FGR
fetal programming
food restriction
metabolic disorders
liver proteomics
author_facet Polyxeni-Maria Sarli
Antigoni Manousopoulou
Elias Efthymiou
Andreas Zouridis
Anastasios Potiris
Panagiota Pervanidou
Konstantinos Panoulis
Nikolaos Vlahos
Efthymios Deligeoroglou
Spiros D. Garbis
Makarios Eleftheriades
author_sort Polyxeni-Maria Sarli
title Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition
title_short Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition
title_full Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition
title_fullStr Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition
title_full_unstemmed Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition
title_sort liver proteome profile of growth restricted and appropriately grown newborn wistar rats associated with maternal undernutrition
publisher Frontiers Media S.A.
series Frontiers in Endocrinology
issn 1664-2392
publishDate 2021-05-01
description 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.
topic FGR
fetal programming
food restriction
metabolic disorders
liver proteomics
url https://www.frontiersin.org/articles/10.3389/fendo.2021.684220/full
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