title: Effects of a trichothecene, T-2 toxin, on proliferation and steroid production by porcine granulosa cells.
abstract: Fusarium mycotoxins, such as trichothecenes and zearalenone, are produced by molds and contaminate a large variety of grains and feedstuffs worldwide. Mycotoxins of Fusarium fungi include the trichothecenes, deoxynivalenol and T-2 toxin (T2), and zearalenone, and have been implicated in poor reproductive performance in pigs. However, direct ovarian effects of T2 toxin have not been reported. Therefore, porcine granulosa cells (GC) from small follicles (1-5mm) were cultured for 2 days in 5% fetal bovine serum and 5% porcine serum-containing medium followed by 2 days in serum-free medium containing various doses of FSH, insulin-like growth factor-I and T2 (at various doses/combinations) to evaluate the influence of T2 on steroid production and cell proliferation. T2 at 1, 3, 30 and 300 ng/mL completely inhibited FSH plus IGF-I-induced estradiol production, whereas 0.3 ng/mL of T2 inhibited estradiol production by 40%. Progesterone production was less sensitive to the inhibitory effects of T2 with 0.3 ng/mL having no effect and 1 ng/mL inhibiting progesterone production by only 30%. At 30 and 300 ng/mL, T2 completely inhibited FSH plus IGF-I-induced progesterone production. The impact of T2 on the dose-response to IGF-I (0, 3, 10 and 30 ng/mL) was also evaluated; T2 blunted the stimulatory effect of 3-30 ng/mL of IGF-I on steroid production and cell proliferation. Serum-induced granulosa cell proliferation was decreased (P<0.05) by 40% after 1 day and by 56% after 2 days of T2 treatment. The present studies indicate for the first time that T2 may be able to alter in growth of the granulosa layer within ovarian follicles in addition to their effect on steroidogenesis. In conclusion, T2 has potent direct dose-dependent effects on granulosa cell proliferation and steroidogenesis. These direct ovarian effects could be one mechanism whereby contaminating Fusarium mycotoxins in feedstuffs could impact reproductive performance in swine.
authors.affiliation: Department of Veterinary Sciences and Technologies for Food Safety, Università degli Studi di Milano, Milan, Italy. francesca.caloni@unimi.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Caloni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ranzenigo
authors.forename: Fausto
authors.initials: F
authors.lastname: Cremonesi
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Spicer
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology; D013256:Steroids / Q000096:biosynthesis*; D013552:Swine; D013605:T-2 Toxin / Q000633:toxicity*; D014255:Trichothecenes / Q000494:pharmacology
chemical_list: D016895:Culture Media, Serum-Free; D013256:Steroids; D014255:Trichothecenes; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D019821:Simvastatin; D013605:T-2 Toxin; C007262:deoxynivalenol