Reproductive tract infections contribute to the development of testicular inflammatory lesions, leading to
male infertility. Previous research shows that the activation of the NLRP3
inflammasome in
orchitis promotes the secretion and maturation of IL-1β and, thus, decreases male fertility. The
calcium-sensing receptor (CaSR) is closely related to the secretion of proinflammatory
cytokines. An increase in the CaSR level promotes the assembly and activation of the NLRP3
inflammasome. However, the role of CaSRs in
orchitis is unknown. We first constructed a uropathogenic Escherichia Coli (UPEC) rat
orchitis model and then detected the expression of CaSR and NLRP3 inflammatory pathway
proteins in testicular macrophages (TM) through RT-PCR and WB,
calcium levels in TM through flow cytometry, and proinflammatory factor IL-1β through ELISA. In addition,
testosterone levels in the serum samples were detected using liquid chromatography-mass spectrometry (LC-MS). Here, we show that CaSR upregulation after
infection in TM in a rat model of UPEC induces the activation of the NLRP3
inflammasome pathway and thereby enhances IL-1β secretion and reduces the
testosterone level in the blood. Moreover, CaSR inhibitors can alleviate inflammatory impairment. After UPEC challenge in vitro, CaSR promoted NLRP3 expression and released IL-1β cleaved from TM into the supernatant. Overall, elevated CaSR levels in TM in testes with UPEC-induced
orchitis may impair
testosterone synthesis through the activation of the NLRP3 pathway and PK2 is an upstream regulatory
protein of CaSR. Our research further shows the underlying mechanisms of
inflammation-related
male infertility and provides anti-inflammatory therapeutic targets for
male infertility.