The Impact of Chemokine-Like Receptor 1 Gene Knockout on Lipopolysaccharide-Induced Epididymo-Orchitis in Mice.

Abstract

This comprehensive study delved into the pivotal function of chemokine-like receptor 1 (CMKLR1) in lipopolysaccharide (LPS)-triggered epididymo-orchitis in mice. Upon LPS exposure, wild-type (WT) mice exhibited marked elevations in serum pro-inflammatory markers, including G-CSF, IL-6, and RANTES, along with heightened levels of TNF-α and IL-6 in testicular and epididymal tissues, which accompanied by pronounced structural damage within the testicular tissue and a concurrent decline in serum testosterone, estradiol (E2) levels, and testicular steroid synthetase expression. Remarkably, Cmklr1 gene ablation intensified the pro-inflammatory response in the serum (especially IFN-γ), testes, and epididymis of epididymo-orchitis models. Furthermore, Cmklr1 deficiency uniquely induced structural alterations within the epididymis, which is absent in the WT model. This genetic manipulation also exacerbated the decline in serum testosterone and E2 levels and testicular steroid synthase activity. While chemerin levels were significantly diminished in WT epididymo-orchitis models, Cmklr1 knockout had no discernible effect on chemerin expression in the model. In addition, a noteworthy observation was the elevation of the serum low density lipoprotein/high density lipoprotein (LDL/HDL) ratio in Cmklr1-deficient mice. Collectively, these findings underscore that the lack of chemerin/CMKLR1 signaling axis could potentially worsen the symptoms during LPS-induced epididymo-orchitis, highlighting its potential as a therapeutic target in related pathologies.