2-Methoxyestradiol alleviates E. coli-induced endometritis in rats via inhibition of TLR-4/MyD88/NF-κB axis.

Endometritis refers to inflammation of uterine endometrial tissues that occurs mainly due to infection affecting the glandular and stromal tissues. It represents a significant cause of infertility in both humans and animals. 2-Methoxyestradiol (2 ME) is a natural derivative of 17β-estradiol (E2) produced in the body, and it is recognized to have remarkable anti-inflammatory properties. This study aimed to explore the possible protective effects of 2 ME against experimentally induced endometritis. Endometritis was induced by inoculating Escherichia coli (E. coli) in rats' uteri. This caused marked histopathological changes as well as oxidative stress. Also, E. coli-induced endometritis was manifested by increased immune expression of tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and myeloperoxidase (MPO). Furthermore, E. coli significantly enhanced endometrial apoptosis as evidenced by modulation of messenger ribonucleic acid (mRNA) expressions of Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) in favor of apoptosis. Intraperitoneal administration of 2 ME (1 or 5 mg/kg) significantly inhibited oxidative stress and suppressed the expression of the inflammatory markers. Further, it inhibited E. coli-induced apoptosis in uterine tissues. Finally, 2 ME significantly inhibited the expression of Toll-like receptor-4 (TLR-4), myeloid differentiation primary response 88 (MyD88), and nuclear factor-kappa B (NF-κB). In conclusion, 2 ME inhibits E. coli-induced endometritis in rats via modulation of the TLR-4/MyD88/NF-κB axis.