T-2 toxin is a secondary metabolite produced by Fusarium genus and has been found to present as common contaminant in food and feedstuffs of cereal origin.Very little information regarding the ovarian effects of T-2 toxin is available.In porcine model T-2 toxin was found to inhibit the steroidogenesis.However, the mechanism has not been well understood.In this study we used rodent model to investigate the effects of T-2 toxin on cAMP-PKA pathway and explored potential mechanism for T-2 toxin induced reproductive toxicity in rats.We first analyzed the the effects of T-2 toxin on progesterone and estrogen production in ratgranulosa cells (GC).For this purpose the GC were cultured for 48 h in 10% fetal bovine serum-containing medium followed by 24 h in serum-free medium containing FSH (10ng/ml), and rostenedione (3 ng/ml) and T-2 toxin (at various doses/combinations).T-2 toxin dose-dependently inhibited the growth of cells and the steroid hormone production.cAMP-PKA pathway is critical of steroidogenesis and we found that cAMP levels was dose-dependently inhibited by T-2 toxin (1-100nmol/L).Furthermore ,we found agonists of cAMP-PKA pathway 8-Br-cAMP and 22R-HC induced progesterone production in GC was abolished by T-2 toxin treatment at low dose (1 nmol/L) suggesting the granulosa cell is highly sensitive to the T-2 toxin.cAMP-stimulated steroidogenic acute regulatory protein (STAR) is rate limiting de novo protein in progesterone synthesis.Exposure to T-2 toxin caused significant suppression of StAR expression as determined by Western and semiquanttive RT-PCR suggesting StAR is a sensitive target for T-2 toxin.Taken together, our results strongly suggest T-2 toxin inhibits steroidogenesis by targeting at StAR protein through suppression of cAMP-PKA pathway.The antisteroidogenesis effects were observable at low T-2 dose (1 ng/ml) suggesting T-2 toxin has an endocrine disruptive effect.