Identification of genes associated with susceptibility to persistent breeding-induced endometritis by RNA-sequencing of uterine cytobrush samples.

The research investigates the genetic factors influencing susceptibility to a horse reproduction condition, Persistent Breeding-Induced Endometritis (PBIE). The study finds a direct link between the levels of expression in specific genes and the susceptibility to or fertility in mares with this condition.

Objective and Methodology

• The study aims to understand the genetic susceptibility to PBIE, a common reproductive disorder in broodmares.
• The researchers used cytobrush samples of uterine tissue from 81 broodmares 1-3 days before artificial insemination (AI).
• They then assessed the susceptibility to PBIE using criteria like the presence of ≥ 2 cm of intrauterine fluid 24 hours after AI and the fertility status of the mares two weeks post-ovulation.
• The researchers divided the mares into three groups:
  • Susceptible non-pregnant (SNP) mares
  • Resistant pregnant (RP) mares
  • Susceptible pregnant (SP) mares
• They then compared RNA expressions across these groups to identify differences.

Key Findings

• Researchers identified 66 differentially expressed genes (DEGs) between SNP and RP mares, and 60 DEGs between SP and SNP mares.
• SNP mares showed lower expressions of genes associated with regulating steroid hormone metabolism and neutrophil chemotaxis compared to RP mares. They had higher expression levels for genes related to uterine inflammation.
• Compared to SNP mares, SP mares had lower expressions of genes tied to extracellular matrix degradation, tissue adhesions, and fibrosis, whilst showing higher expressions for genes related to uterine cell proliferation, differentiation, and angiogenesis.

Implication and Conclusion

• The study suggests that specific transcript levels like apolipoprotein E (APOE), roundabout 2 (ROBO2), cluster domain 44 (CD44), integrin beta 3 (ITGB3), and epidermal growth factor (EGF) could be potential biomarkers for susceptibility to PBIE.
• Additionally, the research suggests higher expressions of fibroblast growth factor 9 (FGF9), kinase domain receptor (KDR), and C-X-C motif chemokine ligand (CXCL) 16, collagen type V alpha 2 (COL5A2), and fibronectin (FN1) could indicate fertility in susceptible mares when supplemented with proper breeding management.
• The study’s results provide critical insights for equine reproductive management, specifically for broodmares susceptible to PBIE. It has the potential to inform effective breeding management strategies, enhancing fertility rates, and lowering PBIE susceptibility.