Involvement of cyclin D1 and E2f1 in zearalenone-induced DNA damage in testis of rats

• Exposure to 2 mg/kg of ZEA exhibits the same phenotype as 17 β-estradiol induces in testicular tissue.
• ZEA at dose level of 1 and 2 mg/kg up-regulates the expression of cyclin D1 and E2f1 expression in the testis.
• ZEA at dose level of 4 mg/kg reduces cyclin D1 and E2f1 expression in the testis.
• ZEA enhances the cellular apoptosis via oppositional roles of cyclin D1 and E2F1 checkpoint machineries.

This study was designed to evaluate the effect of zearalenone (ZEA) on cell cycle checkpoints cyclin D1 and E2f1 expression at mRNA level and to analyze the estrogen like impact of ZEA on male reproductive system.Thirty mature male rats were randomly assigned into five groups as; control (received 0.5 mL saline normal, i.p.), ZEA-received groups (1, 2 and 4 mg/kg, b.w., i.p.) and 17 β-estradiol-received group (0.1 mg/kg, i.p.). All animals received chemicals for 28 days. Cyclin D1 expression was evaluated both by using PCR and immunohistochemistry staining. The mRNA level of E2f1 was also assessed by PCR. Cellular apoptosis was evaluated by using TUNEL and DNA laddering tests.ZEA, at low and medium doses increased the cellular apoptosis and DNA fragmentation. However, at high dose-received animals, severe necrosis was revealed in germinal epithelium. The medium dose of ZEA exhibited the same phenotype as 17 β-estradiol-showed. Accordingly, the medium dose of ZEA-and 17 β-estradiol significantly up-regulated the expression of cyclin D1 and E2f1 in the testis. In contrast, high dose of ZEA down regulated the expression of both genes at mRNA level. The histomorphometric analyses showed that ZEA in medium and high doses remarkably lowered the tubular differentiation and spermiogenesis indices. In conclusion, our data suggest that ZEA enhances the cellular apoptosis likely via oppositional roles of cyclin D1 and E2F1 checkpoint machineries for cell cycles in testicular tissue. Moreover, at medium dose level ZEA exerts the same pathological phenotype as 17 β-estradiol induces.

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