Prenatal transcript levels and metabolomics analyses reveal metabolic changes associated with intrauterine growth restriction and sex

Author:

Ponsuksili Siriluck1ORCID,Murani Eduard1ORCID,Hadlich Frieder1,Iqbal Muhammad Arsalan1,Fuchs Beate2,Galuska Christina E.2,Perdomo-Sabogal Alvaro1,Sarais Fabio1,Trakooljul Nares1,Reyer Henry1,Oster Michael1,Wimmers Klaus13ORCID

Affiliation:

1. Research Institute for Farm Animal Biology (FBN), Institute for Genome Biology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany

2. Research Institute for Farm Animal Biology (FBN), Core Facility Metabolomics, 18196 Dummerstorf, Germany

3. Faculty of Agricultural and Environmental Sciences, University Rostock, 18059 Rostock, Germany

Abstract

The metabolic changes associated with intrauterine growth restriction (IUGR) particularly affect the liver, which is a central metabolic organ and contributes significantly to the provision of energy and specific nutrients and metabolites. Therefore, our aim was to decipher and elucidate the molecular pathways of developmental processes mediated by miRNAs and mRNAs, as well as the metabolome in fetal liver tissue in IUGR compared to appropriate for gestational age groups (AGA). Discordant siblings representing the extremes in fetal weight at day 63 post conception (dpc) were selected from F2 fetuses of a cross of German Landrace and Pietrain. Most of the changes in the liver of IUGR at midgestation involved various lipid metabolic pathways, both on transcript and metabolite levels, especially in the category of sphingolipids and phospholipids. Differentially expressed miRNAs, such as miR-34a, and their differentially expressed mRNA targets were identified. Sex-specific phenomena were observed at both the transcript and metabolite levels, particularly in male. This suggests that sex-specific adaptations in the metabolic system occur in the liver during midgestation (63 dpc). Our multi-omics network analysis reveals interactions and changes in the metabolic system associated with IUGR and identified an important biosignature that differs between IUGR and AGA piglets.

Publisher

The Royal Society

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology,General Neuroscience

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