Melamine induces reproductive dysfunction via down-regulated the phosphorylation of p38 and downstream transcription factors Max and Sap1a in mice testes

Abstract

Melamine poisoning incidents and potential health risks raise global attention. Recent studies imply that melamine exposure is related to male reproductive dysfunction, however, the underlying mechanisms are unclear. In this study, 32 male Kunming mice were administered with 0, 12.5, 25, and 50 mg/L melamine via drinking water for 13 weeks, respectively. Sperm quality, testicular morphology, and the mRNA expression levels of MAPK family members p38, ERK5, ERK1/2, JNK1/2/3 and their downstream transcription factors GADD153, MAX, MEF2C, CREB, c-Myc, JunD, c-JUN, Sap1a, p53, ATF-2, Elk1, and Nur77 in testes were investigated. The results revealed that low-dose melamine exposure reduced sperm quality, altered the testicular histological structure, and reduced the mRNA expression levels of p38, ERK1/2, MAX and Sap1a in the testes. The p38 and phosphorylated-p38 expressions analysis further suggested that the down-regulated phosphorylation of p38 and downstream transcription factors MAX and Sap1a play key roles in male reproductive dysfunction caused by melamine. Altogether, our study provides a new insight to elucidate the underlying mechanisms by which melamine induces male reproductive toxicity, and to evaluate the health risks of melamine.