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

Area of Science:

• Reproductive biology
• Endocrinology
• Cellular and molecular biology

Background:

• The endometrium, crucial for menstruation and pregnancy, is sensitive to hormonal changes.
• Obesity is linked to endometrial dysfunction, impacting women's health and fertility, but mechanisms remain unclear.
• Chemerin, an adipokine, influences immunity and metabolism via its receptors.

Purpose of the Study:

• To investigate the effects of chemerin on human endometrial epithelial cells using RNA sequencing.
• To elucidate the molecular mechanisms underlying chemerin-induced endometrial dysfunction in obesity.

Main Methods:

• Utilized 12Z cells, expressing endometrial and epithelial markers, as a model system.
• Performed RNA sequencing (RNA-Seq) to analyze global gene expression changes.
• Conducted Principal Component Analysis (PCA), Differential Expression Analysis (DEA), and Gene Set Enrichment Analysis (GSEA).

Main Results:

• Chemerin treatment significantly altered the endometrial cell transcriptome.
• Identified 388 differentially expressed genes (DEGs) upon chemerin exposure.
• Observed inhibition of lipid metabolism, induction of epithelial-mesenchymal transition (EMT)-like processes, and cellular senescence.
• Found that chemerin restrains the STAT3 signaling pathway, essential for endometrial receptivity.

Conclusions:

• Overproduced chemerin contributes to endometrial dysfunction in obesity.
• Chemerin disrupts key endometrial functions, including lipid metabolism and STAT3 signaling.
• These findings offer insights into the pathological mechanisms of obesity-related infertility.