ABSTRACT
There is now overwhelming evidence of global contamination of commodities with Fusarium mycotoxins. Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in corn in combination with deoxynivalenol (DON), α-zearalenol (α-ZEA) and ß-zearalenol (ß-ZEA). The aim of this study was to determine if FB1, alone and combined with DON or α-ZEA or ß-ZEA, can affect cell proliferation and steroid production of bovine granulosa cells (GC). A species-specific model with bovine granulosa cells (GC) was used to study the potential endocrine disruptor effects of FB1 alone and in co-exposure. In the presence of ß-ZEA (30 ng/mL), FB1 at 30 ng/mL showed a stimulatory effect on GC numbers. Insulin-like growth factor-1 (IGF1)-stimulated cell proliferation was decreased after exposure to ß-ZEA alone at 5.0 µg/mL and FB1 with α-ZEA and ß-ZEA at the same concentration. Regarding steroid production, FB1 at 30 ng/mL and 100 ng/mL amplified the inhibitory effect of ß-ZEA (30 ng/mL) on estradiol (E2) production, while FB1 alone increased (P < 0.05) IGF1-induced E2 production. α-ZEA alone decreased (P < 0.05) E2 production, whereas ß-ZEA alone and in combination with FB1 decreased (P < 0.05) E2 production. These studies indicate for the first time that the Fusarium mycotoxin FB1 along with other mycotoxins can affect GC proliferation and steroid production, which ultimately could influence reproductive function in cattle.
Subject(s)
Endocrine Disruptors/toxicity , Environmental Pollutants/toxicity , Fumonisins/toxicity , Fusarium , Granulosa Cells/drug effects , Abattoirs , Animals , Cattle , Cell Proliferation/drug effects , Cells, Cultured , Endocrine Disruptors/agonists , Endocrine Disruptors/chemistry , Environmental Pollutants/agonists , Environmental Pollutants/antagonists & inhibitors , Estradiol/agonists , Estradiol/chemistry , Estradiol/metabolism , Female , Fumonisins/agonists , Fumonisins/antagonists & inhibitors , Granulosa Cells/cytology , Granulosa Cells/metabolism , Insulin-Like Growth Factor I/agonists , Insulin-Like Growth Factor I/antagonists & inhibitors , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Osmolar Concentration , Progesterone/agonists , Progesterone/antagonists & inhibitors , Progesterone/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Stereoisomerism , Trichothecenes/agonists , Trichothecenes/toxicity , Zeranol/agonists , Zeranol/analogs & derivatives , Zeranol/toxicityABSTRACT
Bisphenol-A (BPA) is a primary monomer in polycarbonate plastics and epoxy resins. BPA may be released into the environment following its formation via hydrolysis of ester bonds of the polymers. It has been detected in human plasma, placenta, amniotic fluid, amniotic chord, urine and saliva. BPA disrupts normal cell function by acting as an estrogen agonist as well as an androgen antagonist. The present study was carried out to investigate whether BPA can bind to human glucocorticoid receptor (GR) and elucidate its mode of interaction. BPA has been successfully docked in silico into the ligand binding site of GR using the program Discovery Studio 2.0. The structure has been compared with other agonist and antagonist bound structures of GR. It is found that the mode of interactions and binding energy of BPA were similar to that of DEXA and cortisol, two known agonists of GR. This reveals that BPA can bind to GR as an agonist. Hence, BPA may produce biological effects similar to that produced by glucocorticoids.