2. Academic Validation
  3. β-Hydroxybutyric Acid-Induced Bovine Endometrial Epithelial Cell Pyroptosis via Activating P2X7R

β-Hydroxybutyric Acid-Induced Bovine Endometrial Epithelial Cell Pyroptosis via Activating P2X7R

  • J Agric Food Chem. 2025 Aug 27;73(34):21296-21308. doi: 10.1021/acs.jafc.4c07921.
Jiajia Mu 1 2 3,  Qiannan Sun 4 5,  Nanyan Lin 1 2 3,  Chenguang Yue 1 2 3,  Jiaqiao Zhu 1 2 3,  Hui Zou 1 2 3,  Hongyan Zhao 1 2 3,  Ruilong Song 1 2 3,  Zongping Liu 1 2 3,  Yonggang Ma 1 2 3
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P. R. China.
  • 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, P. R China.
  • 3 Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu 225009, P. R China.
  • 4 Medical Research Center, Northern Jiangsu People's Hospital, Yangzhou 225001, China.
  • 5 Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, China.
PMID: 40742321 DOI: 10.1021/acs.jafc.4c07921
Abstract

Ketosis in dairy cows is linked to endometritis, but the molecular mechanisms are unclear. We investigated whether P2X7R is crucial in ketosis-induced endometritis. Ketotic cows had higher levels of NLRP3, Caspase-1, GSDMD, GSDME, and P2X7R in the uterine tissue. β-Hydroxybutyric acid (BHBA) exposure in bovine endometrial epithelial cells induced Pyroptosis, increased Pyroptosis protein and gene expression, and raised Pyroptosis rates. P2X7R levels rose with BHBA, and BHBA also increased the level of extracellular ATP. Inhibitors of NLRP3, Caspase-1, Caspase-3, and P2X7R reduced BHBA-induced Pyroptosis. P2X7R inhibition suppressed NLRP3, Caspase-1, and Caspase-3 activation, preventing Pyroptosis. In P2rx7-/- mice with a ketosis model, blood BHBA was lower, and uterine tissue showed less pyroptosis-related protein expression compared to ketotic mice. P2X7R appears to regulate BHBA-induced Pyroptosis through NLRP3 and Caspase-3 signaling, suggesting it is a potential therapeutic target.

Keywords

P2X7R; bovine endometrial epithelial cells; endometritis; ketosis; pyroptosis.

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