The ameliorative effect of melatonin on LPS-induced Sertoli cells inflammatory and tight junctions damage via suppression of the TLR4/MyD88/NF-κB signaling pathway in newborn calf

Abstract

The blood-testicular barrier (BTB) is involved in spermatogenesis, protects sperm development, and plays a crucial role in the reproductive process. Tight junctions (TJs) between Sertoli cells (SCs) are the key structure of (BTB), and if its structure is damaged, BTB function is affected. The cellular inflammation caused by Gram-negative bacteria affects the structural integrity of TJs. Melatonin (MT) has anti-inflammatory effects; however, the effect of MT in newborn calf SCs is unknown. Therefore, this experiment studied the protective effect of MT. The results showed that LPS upregulated TLR4, MyD88, and NF-κB expressions, in turn, activated the TLR4/MyD88/NF-κB signaling pathway, produced a large amount of IL-6 and IL-1β, downregulated the expression of ZO-1 and Occludin, and reduced the viability of SCs, which resulted in the inflammatory response of SCs and damage of TJs. The addition of MT decreased TLR4, MyD88, and NF-κB expressions, it then inhibited the activation of TLR4/MyD88/NF-κB signaling pathway, downregulated the expression of IL-6 and IL-1β, upregulated the expression of ZO-1 and Occludin, and increased the cell viability, thereby alleviating the inflammatory response of SCs, and restored the TJs structure. Overall, our results reveal that MT can alleviate LPS-induced in newborn calf SCs Inflammation and TJs injury through TLR4/MyD88/NF-κB signaling pathway.