Mare endometrosis induces endometrial proteome changes.

Research Overview

• This study examined changes in protein expression in the uterine lining (endometrium) of mares affected by endometrosis, a common fibrotic condition that impairs horse fertility.
• Researchers identified specific proteins and biological processes linked to the disease, providing insights into its molecular mechanisms and potential pathways for development and progression.

Background and Purpose

• Endometrosis is characterized by excessive fibrosis (scarring) of the mare’s endometrium, leading to reduced fertility—a significant problem in horse breeding.
• The molecular basis of this fibrotic condition is not fully understood, limiting effective diagnosis and treatment options.
• The study aimed to investigate protein changes in the endometrial tissue from mares with different severities of endometrosis (category IIA vs. IIB) to identify involved biological processes and pathways.

Methodology

• Endometrial biopsies were collected from cyclic mares and classified using Kenney and Doig’s system:
  • Category IIA: Mild fibrosis
  • Category IIB: Moderate fibrosis
• Proteomic analysis was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify and quantify proteins present in the tissue samples.
• Differentially abundant proteins (DAPs) were determined using statistical criteria (p < 0.05 and absolute log2 fold change ≥ 1) to compare category IIB vs. IIA samples.
• Western blotting was used to validate the abundance of Histone H2A, one of the proteins significantly changed between categories.

Key Findings

• A total of 100 proteins showed altered abundance in category IIB (moderate fibrosis) compared to category IIA (mild fibrosis) endometrium.
• These proteins were mainly associated with biological processes including:
  • Cell growth and structural organization
  • Apoptotic processes (programmed cell death)
  • Immune response and inflammation
  • Oxidative stress response
• Proteins upregulated in category IIB endometria were enriched in terms related to oxidative stress defense and regulation of epithelial-mesenchymal transition (EMT), which is key in fibrosis development.
• Specific proteins identified as more abundant in advanced endometrosis included:
  • Peroxidasin and glutathione S-transferases (linked to oxidative stress)
  • CD5 molecule-like protein, serpin family proteins, and histone H2A (associated with fibrosis and inflammation)
• Western blot analysis confirmed higher abundance of Histone H2A in category IIB samples, supporting its role in chromatin remodeling and gene regulation during endometrosis.

Implications and Conclusions

• The study provides evidence that oxidative stress and epithelial-mesenchymal transition are important components of endometrosis progression in mares.
• Identified proteins may serve as potential biomarkers or therapeutic targets for the diagnosis and treatment of endometrosis in equine reproductive medicine.
• Understanding these molecular changes enhances knowledge of how endometrial fibrosis disrupts fertility, helping to develop strategies to mitigate its effects in horse breeding.