Evaluating the protective effects of melatonin on di(2-ethylhexyl) phthalate-induced testicular injury in adult mice

Objective: Di (2-ethylhexyl) phthalate (DEHP) is a common phthalate derivative, interfering with normal function of reproductive system. The present study evaluated effects of melatonin on DEHP-induced testicular injury in mice. Design: Thirty-two adult male mice were randomly divided to four groups; group I received normal saline, group II received DEHP, group III received DEHP and melatonin, and group IV was treated with melatonin alone. Body and testes weights, total antioxidant capacity (TAC), glutathione level and superoxide dismutase, glutathione peroxidase and catalase activities were measured. Serum testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and interleukin 1 beta (IL-1 beta) and tumor necrosis factor (TNF-alpha) concentration were evaluated by ELISA assay. Also, malondialdehyde (MDA) and nitric oxide (NO) levels, sperm characteristics and histological changes of testes were analyzed. Results: Body and testes weights were decreased in DEHP group. DEHP also reduced the number of spermatogonia, primary spermatocyte and sertoli cells as well as sperm vitality and progressive motility; these toxic effects were associated with alterations in serum hormone levels. Melatonin remarkably inhibited DEHP-induced reduction of body weight and antioxidant capacity. Melatonin reduced DEHP-induced elevation of NO, MDA, IL-1 beta and TNF-alpha levels. Melatonin improved DEHP-induced changes in hormonal levels, number of sertoli cells, spermatogonia, and sperm viability and motility. Conclusion: Melatonin considerably inhibits DEHP-induced gonadotoxicity through reducing oxidative stress and inflammatory responses. These results suggest that melatonin may be considered as a promising agent to reduce toxic effects of endocrine disrupting chemicals such as DEHP on the male reproductive system.