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RNA Sequencing of Decidua Reveals Differentially Expressed Genes in Recurrent Pregnancy Loss

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Abstract

Recurrent pregnancy loss (RPL) is affecting 3–5% of the women who are expecting to have babies annually. However, the molecular changes of RPL patients have not been well characterized before. In the current study, we aimed to discover the differentially expressed genes (DEGs) in decidua from RPL patients by utilizing RNA sequencing (RNA-seq) technology. Four RPL patients and three control women were recruited to conduct RNA-seq, and 153 genes comprising 69 were upregulated and 84 downregulated showed different expression levels between the health control and RPL groups. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to identify potential biological processes associated with RPL. We recognized that type I interferon signaling pathway and TNF signaling pathway are significantly upregulated in women with RPL. Upregulated expression of MX1, IFI27, and ISG15 in type I interferon signaling pathway and TNFRSF21 in TNF signaling pathway were validated by an extended sample of 15 RPL patients and 12 control women, by quantitative real-time polymerase chain reaction (qRT-PCR). In conclusion, the results of the current study revealed molecular changes in decidua which may reflect the intrauterine circumstance when pregnancy loss happens and potentially contributes to RPL.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

Abbreviations

RPL:

Recurrent pregnancy loss

RIF:

Recurrent implantation failure

DEG:

Differentially expressed gene

RNA-seq:

RNA sequencing

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

PCA:

Principal component analysis

qRT-PCR:

Quantitative real-time polymerase chain reaction

TNFRSF21:

Tumor necrosis factor receptor superfamily member 21

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Acknowledgments

We thank Chaoyang Sun for the great help for bioinformatic analysis during data processing.

Funding

This study was supported by the National Key Research and Development Project (2018YFC1002103).

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Authors and Affiliations

  1. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095#, Wuhan, 430030, People’s Republic of China

    Yuehan Li, Renjie Wang, Meng Wang, Weiming Huang, Chang Liu, Zishui Fang, Shujie Liao & Lei Jin

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  1. Yuehan Li
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  2. Renjie Wang
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  3. Meng Wang
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Contributions

Y. L. designed the experiments. Y. L., R. W., and W. H. performed the experiments. Y. L. performed data analysis, constructed the figures, and drafted the manuscript. S. L. and L. J. assisted in the design of the experiments. M. W. and Z. F. revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Shujie Liao or Lei Jin.

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Ethics Approval

This study was approved by the Institutional Review Board of Tongji Hospital (No. TJ-IRB20181110).

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The authors declare no competing interests.

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Supplementary Information

Fig. S1

Placental marker genes expressed by each sample. Heat map showing relative expression of placental marker genes in each sequenced sample (X24, X44, and X45 belong to the control group; X46, X47, X49, and X50 belong to the RPL group). The placental marker genes were provided by Suryawanshi et al. [27] (PNG 699 kb).

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Li, Y., Wang, R., Wang, M. et al. RNA Sequencing of Decidua Reveals Differentially Expressed Genes in Recurrent Pregnancy Loss. Reprod. Sci. 28, 2261–2269 (2021). https://doi.org/10.1007/s43032-021-00482-w

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