Chemerin's Role in Endometrial Dysfunction: Insights From Transcriptomic Analysis

TL;DR

This study explores how chemerin, a protein linked to obesity, affects endometrial cells, revealing its role in disrupting endometrial function and fertility.

Contribution

The study identifies chemerin's impact on lipid metabolism, epithelial-mesenchymal transition, and STAT3 signaling in endometrial dysfunction.

Findings

Chemerin treatment altered the transcriptome of endometrial epithelial cells, with 388 differentially expressed genes.

Chemerin inhibited lipid metabolism and induced epithelial-mesenchymal transition and cellular senescence.

Chemerin restrained the STAT3 signaling pathway, crucial for endometrial receptivity.

Abstract

Endometrium, the lining of the uterus, changes dynamically in response to fluctuations in ovarian hormones. The proper endocrine environment regulates endometrial functions: menstruation and supporting pregnancy. Obesity is closely related to endometrial dysfunction, which seriously affects women's health and fertility, but the pathological mechanism is unknown. Chemerin is an adipokine involved in multiple biological events such as immunity and metabolism by acting on its functional receptors. This study aimed to characterise the effects of chemerin on human endometrial epithelial cells by RNA‐Seq. 12Z cells were utilised as the model because immunoblot results showed that they expressed endometrial markers, epithelial markers and functional receptors for chemerin. Principal component analysis (PCA) showed that chemerin treatment significantly altered the transcriptome. Differential Expression Analysis found 388 significant differentially expressed genes (DEG) in the chemerin treatment group compared with the controls. Gene Set Enrichment Analysis (GSEA) showed that chemerin inhibited lipid metabolism and induced the epithelial‐mesenchymal transition (EMT)‐like process and cellular senescence. More importantly, GSEA and immunoblots showed that chemerin restrained the STAT3 signalling pathway, which is required for endometrial receptivity establishment. Collectively, these findings provide new evidence that over‐produced chemerin underlying the endometrial dysfunctions in obesity.

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