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Lipid metabolism-related genes as biomarkers and therapeutic targets reveal endometrial receptivity and immune microenvironment in women with reproductive dysfunction

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Background

In recent years, alterations in lipid metabolism are currently considered a hallmark feature of many diseases. However, the role in women with reproductive dysfunction (WRD) remains to be fully elucidated. Here, this study aimed to explore the effect of lipid metabolism-related genes (LMRGs) on endometrial receptivity of WRD.

Methods

This study retrospectively analyzed endometrial receptivity array (ERA) in GEO database. The differential expression genes (DEGs) were obtained by limma differential analysis, and the core genes and corresponding predicted microRNA were obtained through protein–protein interaction (PPI) analysis and TargetScan database, so as to predict the chemical targets of drug therapy. Through the intersection of DEGs and LMRGs, the target gene expression profile was obtained for subsequent consensus clustering analysis and immune analysis. In addition, the immune cell infiltration was assessed by applying the ESTIMATE and MCPcounter algorithm and potential drug targets were obtained from the HERB website.

Results

1473 genes showed differential expression between the groups of WRD and fertile women, and then a large number of lipid metabolism-related pathways and immune-related pathways were enriched. Twelve core genes and corresponding predicted miR-134-3p were obtained; most importantly, we found that these 12 genes were all LMRGs. Through drug target prediction, we obtained three drugs that regulate lipid metabolism and improve blood circulation, namely lovastatin, estrogen, and quercetin. EHHADH (AUC = 0.85) and PTEN (AUC = 0.82) have the best diagnostic performance. UMAP and heatmap revealed large differences between three clusters. LMRGs revealed specific manifestations of WRD in endometrial receptivity and immune microenvironment.

Conclusions

Our study explored the expression pattern of LMRGs in endometrium of WRD, screened the corresponding biomarkers, and proposed the combination of traditional Chinese and Western medicine to improve the endometrial receptivity.

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Authors and Affiliations

  1. Shandong University Cheeloo College of Medicine, Shandong University, Jinan, China

    Yang Liu

  2. College of Clinical Medical Sciences, Dalian Medical University, Dalian, China

    Yanqi Yao, Hangyu Sun, Jiayini Zhao, Hongye Li, Shanlin Wang, Ting Zhang & Meng Meng

  3. The First Affiliated Hospital, Dalian Medical University, Dalian, China

    Shu Zhou

Authors
  1. Yang Liu
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  2. Yanqi Yao
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  3. Hangyu Sun
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  4. Jiayini Zhao
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  5. Hongye Li
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  6. Shanlin Wang
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  7. Ting Zhang
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  8. Meng Meng
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  9. Shu Zhou
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Contributions

SZ: conceptualization.

YL: data curation, methodology, investigation, writing—review and editing.

YY, HS: methodology, validation.

JZ, HL: data curation, investigation.

SW, TZ, MM: data curation, investigation.

Corresponding author

Correspondence to Shu Zhou.

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Liu, Y., Yao, Y., Sun, H. et al. Lipid metabolism-related genes as biomarkers and therapeutic targets reveal endometrial receptivity and immune microenvironment in women with reproductive dysfunction. J Assist Reprod Genet 39, 2179–2190 (2022). https://doi.org/10.1007/s10815-022-02584-z

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  • DOI: https://doi.org/10.1007/s10815-022-02584-z

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