Steroidogenic factor-1 hypermethylation in maternal rat blood could serve as a biomarker for intrauterine growth retardation
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Dong-Mei Wu1,*, Liang-Peng Ma1,3,*, Gui-Li Song2, Yong Long2, Han-Xiao Liu1, Yang Liu1 and Jie Ping1
1Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China
2Key Laboratory of Biodiversity and Conservation of Aquatic Organism, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
3Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, Hubei, China
*These authors have contributed equally to this work
Jie Ping, email: email@example.com
Keywords: steroidogenic factor-1 (SF-1); DNA methylation; intrauterine growth retardation (IUGR); clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9); biomarker
Received: July 11, 2017 Accepted: September 21, 2017 Published: October 10, 2017
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.
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