Identification of potential hub genes associated with recurrent miscarriage through combined transcriptomic and proteomic analysis

Hao-Ran Xu; Long Yang; Yan Gu; Yan Shi; Shu-Han Yang; Jie Gan; Wen-Wen Gu; Xuan Zhang; Jian Wang

doi:10.17305/bb.2024.11158

Authors

Hao-Ran Xu Shanghai Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
Long Yang Shanghai Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
Yan Gu The Second Hospital of Tianjin Medical University, Tianjin, China
Yan Shi Shanghai Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
Shu-Han Yang Shanghai Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
Jie Gan Shanghai Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
Wen-Wen Gu Shanghai Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
Xuan Zhang Shanghai Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China; National Immunological Laboratory of Traditional Chinese Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
Jian Wang Shanghai Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China

DOI:

https://doi.org/10.17305/bb.2024.11158

Keywords:

Recurrent miscarriage, hub genes, decidua, endometrial stromal cells, ISG15

Abstract

Recurrent miscarriage (RM) is currently difficult to prevent and treat due to a lack of comprehensive understanding of its molecular mechanisms. The aim of this study was to identify genes potentially involved in the pathogenesis of RM and to observe their expression in the decidual tissues of RM patients. A total of 1823 differentially expressed genes (DEGs) and 148 differentially expressed proteins (DEPs) in decidual tissues between RM and control groups were identified. Subsequently, DCN, DPT, LUM, MFAP4, and ISG15 were identified from the DEGs/DEPs as RM-related hub genes through systematic bioinformatics analysis. Bioinformatics analysis of the single-cell dataset GSE214607 revealed that the expression of these five hub genes in the decidual stromal cells (DSCs) of RM patients appeared to be upregulated, while the RT-qPCR assay showed that their decidual expression levels were significantly increased in RM patients. Uterine Isg15 expression was significantly increased, whereas the uterine expression of Dcn, Dpt, Lum, and Mfap4 was decreased in LPS-induced early pregnancy loss (EPL) mice. MiR-16-5p, -21-3p, -27a-3p, and -941 were identified as potentially involved in the regulation of these five hub genes, and their decidual expression levels were significantly decreased in RM patients. The abnormally increased ISG15 expression in the decidual tissues of RM patients and uterine tissues of LPS-induced mice was validated by WB analysis. ISG15 expression was significantly reduced during the in vitro decidualization of human endometrial stromal cells (hESCs). Collectively, DCN, DPT, LUM, MFAP4, and ISG15 were identified as RM-related hub genes, and their expression in the decidual tissues of RM patients was significantly increased. The decidualization of hESCs was accompanied by reduced ISG15 expression, suggesting that increased decidual ISG15 expression might lead to EPL by disrupting the decidualization process.