Melamine causes testicular toxicity by destroying blood-testis barrier in piglets.

Melamine (MA) exposure causes male reproductive toxicity, however, the mechanism remains unclear. In this study, we investigated the roles of the blood-testis barrier (BTB) in MA-induced reproductive toxicity in piglets. Male weaned piglets were exposed to MA concentrations of 0, 100, 300, and 1000 mg/kg in the diet for 10 weeks. They were euthanized on days 1, 7 and 14 after the final exposure. Body and organ weights, serum biochemistry and testosterone, gross and histopathological changes, and BTB ultrastructure and integrity were assessed. BTB junction protein expression levels and protein levels of the mitogen-activated protein kinase (MAPK) pathway in testes were measured. We found that MA dose-dependently decreased serum testosterone levels and caused gross and histopathological lesions in the testis and epididymis. Marked BTB damage was evidenced by abnormal changes in BTB ultrastructure and increased BTB permeability. Furthermore, MA decreased the protein levels of ZO-1, occludin, N-cadherin, and connexin-43, paralleled by increased the protein levels of p-Erk, p-JNK and p-p38 in testes, suggesting that MA disrupted BTB by downregulating the expressions of BTB junction proteins, with possible involvement of the MAPK signaling pathway. In conclusion, MA exposure gives rise to testicular toxicity in male piglets through destroying BTB integrity.