Insulin-like growth factor-1 protects preimplantation embryos from anti-developmental actions of menadione.
Menadione is a naphthoquinone used as a vitamin K source in animal feed that can generate reactive oxygen species (ROS) and cause apoptosis. Here, we examined whether menadione reduces development of preimplantation bovine embryos in a ROS-dependent process and tested the hypothesis that actions of menadione would be reduced by insulin-like growth factor-1 (IGF-1). Menadione caused a concentration-dependent decrease in the proportion of embryos that became blastocysts. All concentrations tested (1, 2.5, and 5.0 microM) inhibited development. Treatment with 100 ng/ml IGF-1 reduced the magnitude of the anti-developmental effects of the two lowest menadione concentrations. Menadione also caused a concentration-dependent increase in the percent of cells positive for the TUNEL reaction. The response was lower for IGF-1-treated embryos. The effects of menadione were mediated by ROS because (1) the anti-developmental effect of menadione was blocked by the antioxidants dithiothreitol and Trolox and (2) menadione caused an increase in ROS generation. Treatment with IGF-1 did not reduce ROS formation in menadione-treated embryos. In conclusion, concentrations of menadione as low as 1.0 muM can compromise development of bovine preimplantation embryos to the blastocyst stage of development in a ROS-dependent mechanism. Anti-developmental actions of menadione can be blocked by IGF-1 through effects downstream of ROS generation.
Moss
James I
JI
Department of Animal Sciences, University of Florida, Gainesville, FL, 32611-0910, USA.
Pontes
Eduardo
E
Hansen
Peter James
PJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001755:Blastocyst / Q000378:metabolism; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D024483:Vitamin K 3 / Q000008:administration & dosage / Q000633:toxicity*; D014815:Vitamins / Q000008:administration & dosage / Q000633:toxicity*
D017382:Reactive Oxygen Species; D014815:Vitamins; D007334:Insulin-Like Growth Factor I; D024483:Vitamin K 3