Organelle stress in pyometra: Molecular evidence of endoplasmic reticulum stress and mitochondrial dysfunction

This study aimed to explore the key molecular changes related to endoplasmic reticulum stress and mitochondrial damage in the uterine tissues of bitches with open pyometra. A total of 16 bitches were included in the study, divided into a healthy control group (n = 8) and a pyometra group (n = 8). The results showed that compared with healthy individuals, the mRNA expression. and protein abundance of endoplasmic reticulum stress marker genes PERK, ATF4, CHOP, GRP78 and GRP94 were significantly upregulated in the uterine tissues of bitches with pyometra. At the same time, it was observed that the uterus of dogs with uterine abscesses exhibited significant mitochondrial oxidative damage and ultrastructural changes, and transmission electron microscopy (TEM) revealed mitochondrial autophagy phenomena. Western blot analysis further confirmed that the protein abundance of mitochondrial-related proteins TFAM and COX4 in the uterine tissues of dogs with uterine abscesses increased, while the results of real-time quantitative polymerase chain reaction (RT-qPCR) showed that the expression of oxidative stress-related gene CAT was downregulated. In conclusion, our research results indicate that endometritis is driven by a vicious cycle of excessive endoplasmic reticulum stress and mitochondrial dysfunction. This molecular mechanism may further lead to severe damage of endometrial tissues and inflammatory responses.