Induction of Apoptosis in the Immature Mouse Testes by a Mixture of Melamine and Cyanuric Acid

Abstract

The toxicity of melamine has attracted much attention since the recent outbreaks of renal injury in pets and infants. Previous studies indicated that melamine by itself had low toxicity, whereas a mixture of melamine and cyanuric acid (M+CA) could cause serious renal damage. At present, most researches on the toxicity of M+CA are focused on the kidney. However, little is known about the adverse effects of this mixture on the reproductive system. In the present study, the toxicity of M+CA to testes was investigated. Immature male mice were orally dosed with 0, 0.6, 3, and 15 mg kg−1 d−1 of a 1:1 M+CA for 28 d. Pathological changes occurred in germ cells, such as loose arrangement, reduced numbers and karyopyknosis, indicating that this mixture was toxic to spermatogenesis. Compared with the control group, the TUNEL-positive germ cells increased significantly and the ratio of Bcl-2 to Bax, total antioxidant capacity and superoxide dismutase activity decreased significantly in the 3 and 15 mg kg−1 d−1 M+CA treated group, while the activities of caspase-3, caspase-8 and caspase-9 remained unchanged. The results suggest that M+CA can induce apoptosis in the mice testes. The downregulation of Bcl-2/Bax and oxidative stress may play a pivotal role in the induction of apoptosis by M+CA in mice testes.