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        Genome wide methylation analysis to uncover genes related to recurrent pregnancy loss

        Lixia Zhou,Yudong Pu,Yuxun Zhou,Bin Wang,Ye Chen,Yang Bai,Shuzhen He 한국유전학회 2021 Genes & Genomics Vol.43 No.4

        Background Recurrent pregnancy loss (RPL) refers to two or more consecutive spontaneous abortion before 24 weeks of gestation, representing 1% of couples of childbearing age. Epigenetic factors including dysregulation of DNA methylation of some genes may play a role in RPL. Objective To identify RPL related genes modulated by DNA methylation expressed in decidua and blood. Methods Three decidua samples each from RPL patients and normal controls were recruited to perform genome-wide bisulfte sequencing (GWBS) and transcriptome sequencing. Based on the above results, 22.52 kb of diferential methylation regions (DMRs) from 17 genes were verifed by bisulfte sequencing PCR at specifc region (Hi-MethylSeq) in another 15 decidua (7RPL vs. 8 Controls) and 13 blood (5RPL vs. 8 Controls) samples. Results 23 genes showed signifcantly diferential cytosine methylation status and distinct expression level between PRL patients and healthy controls synergistically. Three signaling pathways were found to be shared between genes with both hypomethylated diferential methylation regions (DMR) and upregulated diferential gene expression (DGE). The results from Hi-MethylSeq showed that the hypermethylation of SGK1 in both blood and decidua samples in RPL patients, which was consistent to its lower expression in endometrium reported earlier. SGK3 and CREB5 also showed modulated methylation level in RPL decidua. Conclusion Our fnding supported that aberrant methylation of SGK1 and CREB5 could be a cause of the dysregulation of these gens in the endometrium, which is one of cause of reproductive failure. The function of SGK3 in reproduction system deserves further investigation.

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