Abstract:

Objective To investigate the reproduction toxicity and molecular mechanisms in male mice after nitrite exposure. Methods Thirty six healthy 2-month-old male mice were divided into control group, low-dose group (60 mg/kg) and high-dose group (120 mg/kg), 12 mice each group. Each mouse was treated with saline or different doses of nitrite by peros once per day for a total of 3 months, and the condition of the mice was monitored every week. The tissue of testis was harvested and the pathological changes of testis were analyzed by HE staining. Immunofluorescence and Western blotting analysis were used to detect the proliferation and apoptosis of testicle cells, DNA methylation and histone deacetylation. Results The body weight of the mice in nitrite treated group increased slowly compared with that in the control group. The coefficients of testicular significant decreased (P<0.01) and the morphology of testis also changed after nitrite exposure. In addition, the proliferation of testis cells was elevated dramatically while the apoptosis of testis cells reduced markedly compared with vehicle. The enzyme expressions of both DNA methylation and histone deacetylation were increased in a dose dependent manner after nitrite treatment (P<0.01).Conclusion Nitrite exposure can inhibit mouse growth and spermatogenic cell proliferation, and induce spermatogenic cell apoptosis, leading to reproductive toxicity in male. The increased DNA methylation and histone deacetylation level indicate that epigenetics may be involved in the process of male reproductive system damage and regulatory mechanism by nitrite exposure.

Key words: Nitrite, Reproductive toxicity, DNA methylation, Histone deacetylation, Western blotting, Mouse