PACAP alleviates the defective epididymis and sperm function in LPS-induced acute mice epididymitis

Abstract Background To investigate the molecular mechanisms by which PACAP alleviates LPS-induced epididymitis, focusing on its anti-inflammatory and antioxidant pathways in the epididymal microenvironment. Methods A mouse model of acute epididymitis was induced by LPS injection. The study assessed the levels of inflammatory markers (IL-6 and TNF-α mRNA) in the cauda epididymis, sperm motility and morphology, morphological alterations in the epididymis, and the expression of inflammation and antioxidant-related genes. PACAP treatment was administered to evaluate its effects on these parameters. Results Results showed elevated levels of IL-6 and TNF-α mRNA in the cauda epididymis due to LPS injection. PACAP treatment effectively reduced these inflammatory markers and improved compromised sperm motility and morphology. PACAP also ameliorated morphological changes in the epididymis and mitigated the LPS-induced increase in leukocyte and macrophage markers. Gene expression analysis revealed that PACAP co-treatment suppressed LPS-induced upregulation of Il-6 and Tnf- α in caput tissues. In cauda tissues, PACAP significantly reduced the expression of LPS-elevated Tnf- α and IL-1β. PACAP up-regulated the antioxidant genes Cat and Sod1, which were down-regulated by LPS. IVF experiments demonstrated that PACAP restored the effects of LPS on sperm-egg fusion and embryo development. In conclusion: PACAP played a crucial role in maintaining epididymal function and sperm quality in the presence of inflammation.