PUBLICATION

Steroidogenic factor-1 hypermethylation in maternal rat blood could serve as a biomarker for intrauterine growth retardation

Authors
Wu, D.M., Ma, L.P., Song, G.L., Long, Y., Liu, H.X., Liu, Y., Ping, J.
ID
ZDB-PUB-171210-6
Date
2017
Source
Oncotarget   8: 96139-96153 (Journal)
Registered Authors
Long, Yong, Song, Guili
Keywords
DNA methylation, biomarker, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), intrauterine growth retardation (IUGR), steroidogenic factor-1 (SF-1)
MeSH Terms
none
PubMed
29221193 Full text @ Oncotarget
Abstract
Intrauterine growth retardation (IUGR) is a common obstetric complication lacking an optimal method for prenatal screening. DNA methylation profile in maternal blood holds significant promise for prenatal screening. Here, we aimed to screen out potential IUGR biomarkers in maternal blood from the perspective of DNA methylation. The IUGR rat model was established by prenatal maternal undernutrition. High-throughput bisulfite sequencing of genomic DNA methylation followed by functional clustering analysis for differentially methylated region (DMR)-associated genes demonstrated that genes regulating transcription had the most significantly changed DNA methylation status in maternal blood with IUGR. Genes about apoptosis and placental development were also changed. Besides increased placental apoptosis, IUGR rats demonstrated the same hypermethylated CpG sites of steroidogenic factor-1 (SF-1, a DMR-associated transcription factor about placenta) promoter in maternal blood and placentae. Further, ff1b, the SF-1 ortholog, was knocked out in zebrafish by CRISPR/Cas9 technology. The knock-out zebrafish demonstrated developmental inhibition and increased IUGR rates, which confirmed the role of SF-1 in IUGR development. Finally, hypermethylated SF-1 was observed in human maternal blood of IUGR. This study firstly presented distinct DNA methylation profile in maternal blood of IUGR and showed hypermethylated SF-1 could be a potential IUGR biomarker in maternal rat blood.
Genes / Markers
Figures
Figure Gallery (1 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
ABchemical treatment: caffeineLong-pec
ABchemical treatment: caffeineProtruding-mouth
ABchemical treatment: nicotineLong-pec
ABchemical treatment: nicotineProtruding-mouth
nr5a1azf2083/+ (AB)standard conditions5-9 somites
nr5a1azf2083/+ (AB)standard conditions5-9 somites
nr5a1azf2083/+ (AB)standard conditionsDay 6
nr5a1azf2083/+ (AB)standard conditionsDay 6
nr5a1azf2083/+ (AB)standard conditionsDay 6
nr5a1azf2083/+ (AB)standard conditionsDay 6
1 - 10 of 14
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf2083
    		Complex
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    nr5a1aCRISPR1-nr5a1aCRISPR
    1 - 1 of 1
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    Fish
    Fish
    AB
    nr5a1azf2083/+ (AB)
    1 - 2 of 2
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    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available
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    Citation
    Wu, D.M., Ma, L.P., Song, G.L., Long, Y., Liu, H.X., Liu, Y., Ping, J. (2017) Steroidogenic factor-1 hypermethylation in maternal rat blood could serve as a biomarker for intrauterine growth retardation. Oncotarget. 8:96139-96153.