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

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Abstract

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 bisulfite sequencing (GWBS) and transcriptome sequencing. Based on the above results, 22.52 kb of differential methylation regions (DMRs) from 17 genes were verified by bisulfite sequencing PCR at specific region (Hi-MethylSeq) in another 15 decidua (7RPL vs. 8 Controls) and 13 blood (5RPL vs. 8 Controls) samples.

Results

23 genes showed significantly differential 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 differential methylation regions (DMR) and upregulated differential 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 finding 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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Acknowledgement

This work was supported by Social Technology Development (major) Project in Dongguan (NO 201750715024450), Guangdong Province. We thank Lifang Mo, Huanhou Su, Jinru Cao, and other colleagues for their help in the course of the experiment.

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Authors and Affiliations

  1. Obstetrics, Songshan Lake Central Hospital, No 1 Xianglong Road, Shilong Town, Dongguan, 523326, Guangdong, China

    Lixia Zhou, Yudong Pu & Shuzhen He

  2. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China

    Yuxun Zhou & Bin Wang

  3. Shanghai Biowing Applied Biotechnology Co., Ltd, Shanghai, China

    Ye Chen & Yang Bai

Authors
  1. Lixia Zhou
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  2. Yudong Pu
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  3. Yuxun Zhou
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  4. Bin Wang
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  5. Ye Chen
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  6. Yang Bai
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  7. Shuzhen He
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Correspondence to Shuzhen He.

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Lixia Zhou, Yudong Pu, Yuxun Zhou, Bin Wang, Ye Chen, Yang Bai and Shuzhen He declare that they have no conflict of interest.

Ethical approval

This study had been approved by the Ethics Committee of Songshan Lake Central Hospital, Dongguan, Informed consent was obtained from all individual participants included in the study.

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Zhou, L., Pu, Y., Zhou, Y. et al. Genome wide methylation analysis to uncover genes related to recurrent pregnancy loss. Genes Genom 43, 361–369 (2021). https://doi.org/10.1007/s13258-020-01020-9

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  • DOI: https://doi.org/10.1007/s13258-020-01020-9

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