P-96: Appositional Expressions of Cyclin D1 and E2F1 Gene Machineries in Mycooestrogen Zeralenone-Induced Apoptosis in Testicular Tissue of Rats

Background: Zearalenone (ZEA) is known as a nonsteroidal oestrogenic mycotoxin produced by different species of Fusarium fungi. ZEA is known for its competitive effects with the natural 17-β estradiol to bind with the specific binding sites of the estrogen receptors (Ers). On the other hand, the cyclin family (especially cyclin D1) and E2F1 genes are the checkpoint genes involved in cell cycle. The Ers are directly involved in controlling the checkpoint genes expression. The present study was designed to uncover the effect of ZEA on cyclin D1 and E2F1 genes expression. Materials and Methods: Thirty mature male rats were divided into four groups including; control-sham (2 mL, normal slain, ip), low dose ZEA-treated (1mg/kg, ip), medium dose ZEA-treated (2mg/kg, ip), high dose ZEA-treated (4mg/kg, ip). All animals received chemicals for 21 continuous days. The mRNA levels of cyclin D1 and E2F1 were analyzed using semi-quantitative RT-PCR. The cyclin D1 protein expression was evaluated in germinal epithelium by using immunohistochemical analyzes. The cellular apoptosis in testicular tissue was evaluated by using DNA laddering test. Results: Low and high dose ZEA-treated animals showed cyclin D1 and E2F1 over-expression, while the animals in medium dose ZEA-treated group exhibited a remarkable reduction in cyclin D1 expression. However, the E2F1 over-expression was manifested in medium dose ZEA-received group. ZEA, in dose dependent manner, resulted in intensive DNA fragmentation. Conclusion: Our data showed that, ZEA affects the cyclin D1 and E2F1 genes expression. Accordingly, cyclin D1 promotes the apoptotic pathway in low and high doses and competes with natural 17-β estradiol in low dose of administration and in turn provokes cellular arrest. However, by different mechanism followed by severe DNA damage, over/reduced-expression of E2F1 stimulates cellular cycle arrest in ZEA-induced testicles.