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

Ming Yu1, Yichun Wang1,2, Jinxuan Cai1,3

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Obesity-related endometrial dysfunction may stem from excess chemerin. This adipokine disrupts lipid metabolism, promotes cellular changes, and inhibits the STAT3 pathway crucial for pregnancy.

Keywords:
12Z cellsadipokinechemerinendometrial receptivitytranscriptomic analysis

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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.