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Dysfunctional intercellular communication and metabolic signaling pathways in thin endometrium

Authors :
Liang Xu
Yingying Fan
Jianjun Wang
Rui Shi
Source :
Frontiers in Physiology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Background: The endometrial thickness is a key factor for successful implantation. Thin endometrium is associated with lower implantation rate and pregnancy rate. Lacking of a better understanding for the cellular and molecular mechanisms of thin endometrium, managing patients with thin endometrium still represents a major challenge for clinicians.Methods: In this study, we combined four single-cell RNA sequencing (scRNA-seq) and one bulk sequencing (bulk-seq) data for thin endometrium to perform an integrated analysis for endometrial cells in proliferating phase. Cell proportion and differentially expressed genes (DEGs) were analyzed to determine the disease-specific cell type and signaling pathways. The cell-cell communication among cell types were inferred by “CellChat” to illustrate the differential intercellular communication under normal and thin endometrium conditions. GSEA and GSVA were applied to identify dysfunctional signals and metabolic pathways before and after thin endometrium.Results: Integration of scRNA-seq identified eight cell types. The proportion of stromal cells showed a significant difference between normal and thin endometrial tissue. The DEGs in diverse cell types revealed enriched pathways in a cell-specific manner. Aberrant cell-cell signaling transduction was found in almost all cell types, especially in immune cells and epithelial cells. Furthermore, dysfunctional metabolic signaling pathways were induced in a cell-type dependent way. The down-regulation of carbohydrate metabolism and nucleotide metabolism was observed and the energy metabolism switch was indicated.Conclusion: Conclusively, we discover dysfunctional signals and metabolic pathways in thin endometrium, providing insight into mechanisms and therapeutic strategies for the atrophic endometrium.

Details

Language :
English
ISSN :
1664042X
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Physiology
Publication Type :
Academic Journal
Accession number :
edsdoj.fd36dff84a704b7a88ca2c20ccaf5fb2
Document Type :
article
Full Text :
https://doi.org/10.3389/fphys.2022.1050690