Developmental programming in human umbilical cord vein endothelial cells following fetal growth restriction

Autor: Fieke Terstappen, Jaap A. Joles, Torsten Plösch, Bas B. van Rijn, Jorg J. A. Calis, Michal Mokry, A. Titia Lely, Nina D. Paauw
Přispěvatelé: Obstetrics & Gynecology, Center for Liver, Digestive and Metabolic Diseases (CLDM), Reproductive Origins of Adult Health and Disease (ROAHD)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Epigenomics
Male
Galectin 1
NRM
Umbilical vein
Transcriptome
0302 clinical medicine
Pregnancy
Gene expression
Prospective Studies
RNA-Seq
Genetics (clinical)
DNA methylation
Fetal Growth Retardation
Fetal growth restriction
Nuclear Proteins
Methylation
Human umbilical cord vein endothelial cells
Cardiovascular Diseases
030220 oncology & carcinogenesis
Epigenetics
Female
Kidney Diseases
RNA
Long Noncoding
Adult
Gene set enrichment analysis
FPR3
RNA-sequencing
Biology
Developmental programming
Andrology
03 medical and health sciences
Fetus
Sex differences
Genetics
Human Umbilical Vein Endothelial Cells
Humans
Molecular Biology
Gene
LGALS1
Research
Gene Expression Profiling
Membrane Proteins
Placental Insufficiency
Receptors
Formyl Peptide
Pregnancy Complications
030104 developmental biology
Gene Expression Regulation
Case-Control Studies
CpG Islands
Developmental Biology
Zdroj: Clinical Epigenetics, 12(1):185. BioMed Central Ltd.
Clinical Epigenetics
Clinical Epigenetics, 12(1):185. BMC
ISSN: 1868-7083
1868-7075
Popis: Background Fetal growth restriction (FGR) is associated with an increased susceptibility for various noncommunicable diseases in adulthood, including cardiovascular and renal disease. During FGR, reduced uteroplacental blood flow, oxygen and nutrient supply to the fetus are hypothesized to detrimentally influence cardiovascular and renal programming. This study examined whether developmental programming profiles, especially related to the cardiovascular and renal system, differ in human umbilical vein endothelial cells (HUVECs) collected from pregnancies complicated by placental insufficiency-induced FGR compared to normal growth pregnancies. Our approach, involving transcriptomic profiling by RNA-sequencing and gene set enrichment analysis focused on cardiovascular and renal gene sets and targeted DNA methylation assays, contributes to the identification of targets underlying long-term cardiovascular and renal diseases. Results Gene set enrichment analysis showed several downregulated gene sets, most of them involved in immune or inflammatory pathways or cell cycle pathways. seven of the 22 significantly upregulated gene sets related to kidney development and four gene sets involved with cardiovascular health and function were downregulated in FGR (n = 11) versus control (n = 8). Transcriptomic profiling by RNA-sequencing revealed downregulated expression of LGALS1, FPR3 and NRM and upregulation of lincRNA RP5-855F14.1 in FGR compared to controls. DNA methylation was similar for LGALS1 between study groups, but relative hypomethylation of FPR3 and hypermethylation of NRM were present in FGR, especially in male offspring. Absolute differences in methylation were, however, small. Conclusion This study showed upregulation of gene sets related to renal development in HUVECs collected from pregnancies complicated by FGR compared to control donors. The differentially expressed gene sets related to cardiovascular function and health might be in line with the downregulated expression of NRM and upregulated expression of lincRNA RP5-855F14.1 in FGR samples; NRM is involved in cardiac remodeling, and lincRNAs are correlated with cardiovascular diseases. Future studies should elucidate whether the downregulated LGALS1 and FPR3 expressions in FGR are angiogenesis-modulating regulators leading to placental insufficiency-induced FGR or whether the expression of these genes can be used as a biomarker for increased cardiovascular risk. Altered DNA methylation might partly underlie FPR3 and NRM differential gene expression differences in a sex-dependent manner.
Databáze: OpenAIRE
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