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Purpose: Nicotine can induce sub fertility or infertility both in males and females. The aim of this study is to evaluate the proliferative activity of adult mouse male germ cells following treatment with different doses of nicotine.Materials and Methods: Adult male NMRI mice were divided into four groups. The control group received normal saline and the other animals in groups of 2, 3 and 4 were treated with nicotine in doses of 0.1, 0.2 and 0.4 mg/Kg, respectively.Nicotine was administered intraperitoneally once a day for 14 days. All animals were dissected on 15th day, and evaluations were made by Ki67 immunohistochemistry staining and Johnson’s scoring for assessment of proliferative activity of mitotic & meiotic spermatogenic cells and evaluation of quality of spermatogenesis respectively, and Elisa test for serum testosterone level.Statistical analyses were performed using ANOVA and Tukey tests.Results: Nicotine in doses of 0.2 mg/Kg and 0.4 mg/Kg significantly reduced Johnson's score in comparison with that of control group (p<0.05).Nicotine in dose of 0.2 and 0.4 mg/Kg significantly reduced ki67 index in meiotic leptotene and pachytene cells in comparison with that of control group.However it was not effective on spermatogonia cells. Serum levels of testosterone in groups of 3 and 4 were significantly reduced compared to that of control group (p<0.05). Conclusion: This study indicates that nicotine has adverse effects on spermatogenesis process and it acts in a dose dependent manner. However, in lower doses, proliferative activity is not altered; therefore, it seems that probablility of the other mechanisms are involved in reducing of maturity and quality of spermatogenesis.

Keywords: Nicotine, Proliferation, Testis, Spermatogenesis Quality

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