Dataset Information

Periconceptual Maternal Nutrition Affects Fetal Liver Programming of Energy- and Lipid-Related Genes.

ABSTRACT: During pregnancy, the fetus relies on the dam for its nutrient supply. Nutritional stimuli during fetal organ development can program hepatic metabolism and function. Herein, we investigated the role of vitamin and mineral supplementation (VTM or NoVTM-at least 71 days pre-breeding to day 83 of gestation) and rate of weight gain (low (LG) or moderate (MG)-from breeding to day 83) on the fetal liver transcriptome and the underlying biological pathways. Crossbred Angus beef heifers (n = 35) were randomly assigned to one of four treatments in a 2 × 2 factorial design (VTM_LG, VTM_MG, NoVTM_LG, and NoVTM_MG). Gene expression was measured with RNA-Seq in fetal livers collected on day 83 ± 0.27 of gestation. Our results show that vitamin and mineral supplementation and rate of weight gain led to the differential expression of hepatic genes in all treatments. We identified 591 unique differentially expressed genes across all six VTM-gain contrasts (FDR ≤ 0.1). Over-represented pathways were related to energy metabolism, including PPAR and PI3K-Akt signaling pathways, as well as lipid metabolism, mineral transport, and amino acid transport. Our findings suggest that periconceptual maternal nutrition affects fetal hepatic function through altered expression of energy- and lipid-related genes.

SUBMITTER: Diniz WJS

PROVIDER: S-EPMC9951695 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Periconceptual Maternal Nutrition Affects Fetal Liver Programming of Energy- and Lipid-Related Genes.

Diniz Wellison J S WJS Ward Alison K AK McCarthy Kacie L KL Kassetas Cierrah J CJ Baumgaertner Friederike F Reynolds Lawrence P LP Borowicz Pawel P PP Sedivec Kevin K KK Kirsch James D JD Dorsam Sheri T ST Neville Tammi L TL Forcherio J Chris JC Scott Ronald R Caton Joel S JS Dahlen Carl R CR

Animals : an open access journal from MDPI 20230209 4

During pregnancy, the fetus relies on the dam for its nutrient supply. Nutritional stimuli during fetal organ development can program hepatic metabolism and function. Herein, we investigated the role of vitamin and mineral supplementation (VTM or NoVTM-at least 71 days pre-breeding to day 83 of gestation) and rate of weight gain (low (LG) or moderate (MG)-from breeding to day 83) on the fetal liver transcriptome and the underlying biological pathways. Crossbred Angus beef heifers (<i>n</i> = 35) ...[more]

PMID: 36830387

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Project description:BackgroundMaternal obesity significantly influences fetal development and health later in life; however, the molecular mechanisms behind it remain unclear. This study aims to investigate signature genes related to maternal obesity and fetal programming based on a genomic-wide transcriptional placental study using a combination of different bioinformatics tools.MethodsThe dataset (GSE128381) was obtained from Gene Expression Omnibus (GEO). The data of 100 normal body mass index (BMI) and 27 obese mothers were included in the analysis. Differentially expressed genes (DEGs) were evaluated by limma package. Thereafter, functional enrichment analysis was implemented. Then, weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) analysis were used to further screening of signature genes. Simple linear regression analysis was used to assess the correlation between signature genes and newborn birth weight. Gene set enrichment analysis (GSEA) was implemented to study signaling pathways related to signature genes. The expression of the signature genes was also explored in 48 overweight mothers in the same dataset.ResultsA total of 167 DEGs were obtained, of which 122 were up-regulated while 45 were down-regulated. The dataset was then clustered into 11 modules by WGCNA, and the MEbrown was found as the most significant module related to maternal obesity and fetal programming (cor = 0.2, p = 0.03). The LASSO analysis showed that PTX3, NCF2, HOXB5, ABCA6, and C1orf162 are signature genes related to maternal obesity and fetal programming, which were increased in the placenta of obese mothers compared to those with normal BMI. The area under the curve (AUC) of the signature genes in the receiver operating characteristic curve (ROC) was 0.709, 0.660, 0.674, 0.667, and 0.717, respectively. Simple linear regression analysis showed that HOXB5 was associated with newborn birth weight. GSEA analysis revealed that these signature genes positively participate in various signaling pathways/functions in the placenta.ConclusionPTX3, NCF2, HOXB5, ABCA6, and C1orf162 are novel signature genes related to maternal obesity and fetal programming, of which HOXB5 is implicated in newborn birth weight.

Dataset Information

Periconceptual Maternal Nutrition Affects Fetal Liver Programming of Energy- and Lipid-Related Genes.

Publications

Periconceptual Maternal Nutrition Affects Fetal Liver Programming of Energy- and Lipid-Related Genes.

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