Int J Med Sci 2022; 19(3):546-562. doi:10.7150/ijms.69648 This issue

Research Paper

Investigation and Validation of Molecular Characteristics of Endometrium in Recurrent Miscarriage and Unexplained Infertility from a Transcriptomic Perspective

Yuxin Ran1,2,3#, Jie He1,2,3#, Ruixin Chen4#, Yan Qin5, Zheng Liu1,2,3, Yunqian Zhou1,2,3, Nanlin Yin2,3,6✉, Hongbo Qi1,7✉, Wei Zhou7✉

1. Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
2. Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing 400016, China.
3. Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
4. Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu 610041, China.
5. Department of Gynecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
6. Center for Reproductive Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
7. Department of Obstetrics, Chongqing Health Center for Women and Children, Chongqing 401147, China.
# These authors have contributed equally to this work

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Citation:
Ran Y, He J, Chen R, Qin Y, Liu Z, Zhou Y, Yin N, Qi H, Zhou W. Investigation and Validation of Molecular Characteristics of Endometrium in Recurrent Miscarriage and Unexplained Infertility from a Transcriptomic Perspective. Int J Med Sci 2022; 19(3):546-562. doi:10.7150/ijms.69648. Available from https://www.medsci.org/v19p0546.htm

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Abstract

Graphic abstract

Recurrent miscarriage (RM) and unexplained infertility (UI) are gordian knots in reproductive medicine, which are troubling many patients, doctors, and researchers. Although these two diseases of early pregnancy have a significant impact on human reproductive health, little is known about the specific mechanisms, which caused treatment difficulties. This study focused on the molecular signatures underlying the pathological phenotypes of two diseases, with the hope of using statistical methods to identify the significant core genes. An unbiased Weighted Correlation Network Analysis (WGCNA) algorithm was used for endometrial transcriptome data analysis and the disease-related gene modules were screened out. Through enrichment analysis of the candidate genes, we found similarities between both diseases and shared enrichment of immune-related pathways. Therefore, we used immune algorithms to assess the infiltration of immune cells and found abnormal increases of CD8+T cells and neutrophils. In order to explore the molecular profile behind the immunophenotypic changes, we used the SVM algorithm and LASSO regression to identify the core genes with diagnostic capacity in both diseases and discussed their significance of immune disorders in the endometrium. In the end, the satisfactory diagnostic ability of these core genes was verified in the broader group. Our results demonstrated the presence of immune disorders in non-pregnancy tissues of RM and UI, and identified the core molecules of this phenotype, and discuss mechanisms. This provides exploratory evidence for the in-depth understanding of the mechanism of RM and UI and may provide potential targets for their future treatment.

Keywords: Recurrent miscarriage, Unexplained infertility, Molecular characteristics, Endometrium, Transcriptome analysis.