The uterus has a strong self-regulatory capacity that maintains immune homeostasis and self-tolerance by balancing antimicrobial defense with protection against excessive inflammation. Escherichia coli (E. coli) is the major etiological agent of bovine endometritis, which severely impairs reproductive performance and causes substantial economic losses. The α7 nicotinic acetylcholine receptor (α7nAChR) has been implicated in the regulation of infectious and inflammatory diseases; however, its role in E. coli-induced bovine endometritis remains incompletely understood. In this study, E. coli-infected bovine neutrophils and endometrial tissue models were established to investigate the potential regulatory role of α7nAChR in infection-induced uterine inflammation. α7nAChR was highly expressed in normal bovine neutrophils and endometrial tissues, but was markedly reduced following E. coli infection. E. coli markedly increased inflammatory cytokine levels, whereas pretreatment with PNU-282987 (an α7nAChR agonist) reduced these levels, while pretreatment with MLA (an α7nAChR antagonist) further enhanced them. Western blot analysis showed that α7nAChR activation was associated with increased phosphorylation of JAK2 and STAT3 and reduced phosphorylation of ERK, p38, and p65. In addition, activation of α7nAChR alleviated E. coli-induced bovine endometrial injury, whereas its blockade aggravated inflammatory damage. Collectively, these findings suggest that α7nAChR may regulate inflammatory responses and exert protective effects in E. coli-induced bovine endometritis, possibly through the JAK2/STAT3, MAPK, and NF-κB pathways.

To Cite This Article: Zhao F, Zhang Z, Ren X, Wang J, Li J, Xing L, Mohamed RAEH, Al-Shahari EA, Zhuo M, Yang H and Gao R, 2026. The α7 nicotinic acetylcholine receptor maintains uterine immune tolerance during Escherichia coli-induced bovine endometritis. Pak Vet J, 46(4): 876-87. http://dx.doi.org/10.29261/pakvetj/2026.087