The role of BMI1 in assessing endometrial receptivity and its clinical implications

Endometrial receptivity lacks robust biomarkers. Given its role in stabilizing the progesterone receptor, the epigenetic regulator BMI1 is a key candidate, yet its clinical potential is undefined. This study aimed to characterize BMI1's expression and functional role in receptivity and evaluate its utility as a biomarker for predicting reproductive outcomes.

Endometrial tissues were obtained from patients with elective (EA, n = 78) and spontaneous abortion (SA, n = 39). BMI1 levels, measured by immunohistochemistry (IHC), quantitative real-time PCR (qPCR), and western blot (WB), demonstrated diagnostic value by Receiver Operating Characteristic (ROC) analysis and predicted superior reproductive outcomes in a two-year infertile patient cohort (n = 50).

BMI1 expression was significantly downregulated at both the mRNA and protein levels in the SA compared to the EA group (p < 0.05), with predominant localization in the endometrial epithelium. This was accompanied by significant downregulation of upstream regulators (PR, E6AP) and downstream effectors (GATA6, NANOG) in the SA group, indicating impaired BMI1 pathway activity. ROC analysis confirmed the diagnostic utility of BMI1 for assessing receptivity. Clinical follow-up revealed that BMI1-positive patients had significantly higher rates of bio-chemical pregnancy, clinical pregnancy, and live birth compared to BMI1-negative patients.

Our findings establish BMI1 as a critical regulator of endometrial receptivity, through its role in modulating progesterone signaling. The strong correlation between BMI1 status and pregnancy outcomes highlights its potential as a novel prognostic biomarker for infertility, offering new insights for diagnostic and therapeutic strategies in reproductive medicine.