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DNA Methylation and gene expression patterns are widely altered in fetal growth restriction and associated with FGR development.

ABSTRACT: Fetal growth restriction (FGR) is the failure of the fetus toachieve its genetically determined growth potential, which increasesrisks for a variety of genetic diseases, such as type 2 diabetes mellitus, coronary artery disease, and stroke, during the lifetime. The dysregulation of DNA methylationis known to interact with environmental fluctuations, affect gene expressions comprehensively, and be fatal to fetus development in specific cases. Therefore, we set out to find out epigenetic and transcriptomic alterations associated with FGR development. We found a set of differentially expressed genes associated with differentially methylated regions in placentae and cord blood samples. Using dimensional reduction analysis, the expression and methylation variables of the epigenetically altered genes classified the FGR samples from the controls. These genes were also enriched in the biological pathways such as metabolism and developmental processes related to FGR. Furthermore, three genes of INS, MEG3, and ZFP36L2 are implicated in epigenetic imprinting, which has been associated with FGR. These results strongly suggest that DNA methylation is highly dysregulated during FGR development, and abnormal DNA methylation patterns are likely to alter gene expression.

SUBMITTER: Lee S

PROVIDER: S-EPMC8253195 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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DNA Methylation and gene expression patterns are widely altered in fetal growth restriction and associated with FGR development.

Lee Seoyeong S Kim Young Nam YN Im DoHwa D Cho Su Han SH Kim Jiyeon J Kim Jeong-Hyun JH Kim Kwoneel K

Animal cells and systems 20210517 3

Fetal growth restriction (FGR) is the failure of the fetus toachieve its genetically determined growth potential, which increasesrisks for a variety of genetic diseases, such as type 2 diabetes mellitus, coronary artery disease, and stroke, during the lifetime. The dysregulation of DNA methylationis known to interact with environmental fluctuations, affect gene expressions comprehensively, and be fatal to fetus development in specific cases. Therefore, we set out to find out epigenetic and trans ...[more]

PMID: 34262655

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Project description:BackgroundThis systematic review investigates potential differences in brain development between growth restricted (FGR)-fetuses compared to appropriate for gestational age (AGA) fetuses using MRI.MethodsPubMed, Embase, Cochrane Library and Web of Science databases were searched from 1985 to 2023. FGR was defined as an estimated fetal weight (EFW) < p10 and/or an abdominal circumference (AC) < p10, or 20% reduction in EFW or AC using a minimum interval of two weeks. Outcomes included volumetrics, biometrics, apparent diffusion coefficients (ADC), 1H-MRS-metabolites, and oxygenation of the fetal brain. Risk of bias was assessed using Newcastle-Ottawa Scale (NOS). A meta-analysis was conducted on variables when reported in at least three studies, calculating the mean difference (MD) with a 95% confidence interval (CI).ResultsTwenty-nine studies were included after three-phase screening, 13 used the FGR consensus definition according to the Delphi procedure. Total brain volume and cerebellar volume were significantly reduced in FGR fetuses (n = 183; 74) when compared to AGA fetuses (n = 283; 166) with a MD of -30.84 cm3 (p < 0.01) and - 2.24 cm3 (p < 0.01). ADC values in the frontal white matter (FWM), occipital white matter (OWM), temporal white matter (TWM), thalami, centrum semiovale (CSO), basal ganglia, pons and cerebellum, significantly lower in growth restricted fetuses (-0.07 × 10-3 mm2/s (p < 0.01); -0.06 × 10-3 mm2/s (p < 0.01); -0.07 × 10-3 mm2/s (p < 0.01); -0.10 × 10-3 mm2/s (p < 0.01); -0.06 × 10-3 mm2/s (p < 0.01); -0.07 × 10-3 mm2/s (p < 0.01); -0.07 × 10-3 mm2/s (p < 0.01); -0.02 × 10-3 mm2/s (p < 0.01); respectively). 1H-MRS showed reduced levels of N-acetyl aspartate (NAA): Choline (Cho) and NAA: Creatine(CR) levels in the frontal lobe and central brain tissue, whilst contradictive findings concerning Cho: Cr and Inositol(Ino): Cho ratios were found. Two studies investigated the cerebral hemodynamic changes in FGR fetuses showing no difference in fractional moving blood volume, similar venous blood oxygenation in the superior sagittal sinus and no difference in T2* in the fetal brain.DiscussionMRI provides additional information on fetal brain development in a growth restricted population. Smaller total brain and cerebellar volumes and lower ADC values in the FWM, OWM, TWM, thalami, CSO, basal ganglia, pons and cerebellum have been observed in FGR. These conclusions are drawn on relatively small sample sizes with high heterogeneity resulting from diverse study populations and MRI techniques. Furthermore, how these findings correlate to long-term neurocognitive abnormalities associated with FGR remains to be elucidated. A large cohort study comparing brain maturation, myelination, metabolic and hemodynamic status between brain-sparing FGR fetuses to healthy age-matched controls is needed.

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DNA Methylation and gene expression patterns are widely altered in fetal growth restriction and associated with FGR development.

Publications

DNA Methylation and gene expression patterns are widely altered in fetal growth restriction and associated with FGR development.

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