RESUMO
Man-made magnetic fields (MFs) may exert adverse effects on mammalian embryonic development. Herein, we analysed the effect of 10mT 50Hz sinusoidal (AC) or static (DC) MFs versus 1mT MFs on embryonic development of mice. Exposure for 20days during gestation to 10mT MFs increased resorptions and dead fetuses, decreased crown-rump length and fresh weight, reduced blood vessel differentiation and caused histological changes, accompanied with diminished vascular endothelial growth factor (VEGF) protein expression in several organs. In embryonic stem (ES) cell-derived embryoid bodies exposure towards 10mT MFs increased reactive oxygen species (ROS), decreased vascular marker as well as VEGF expression and enhanced apoptosis. In conclusion, our combined data from in vivo and in vitro experiments identified VEGF as an important mediator during embryonic development that can be influenced by high strength MFs, which in consequence leads to severe abnormalities in fetus organs and blood vessel formation.
Assuntos
Desenvolvimento Embrionário , Campos Magnéticos , Neovascularização Fisiológica , Animais , Linhagem Celular , Estatura Cabeça-Cóccix , Perda do Embrião , Embrião de Mamíferos , Corpos Embrioides/metabolismo , Olho/embriologia , Olho/metabolismo , Feminino , Fígado/embriologia , Fígado/metabolismo , Pulmão/embriologia , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Células-Tronco Embrionárias Murinas/metabolismo , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Aumento de PesoRESUMO
Electromagnetic fields (EMFs) are used to treat bone diseases. Herein, the effects of static EMFs on chondroosteogenesis and vasculogenesis of embryonic stem (ES) cells and bone mineralization of mouse fetuses were investigated. Treatment of differentiating ES cells with static EMFs (0.4-2 mT) stimulated vasculogenesis and chondro-osteogenesis and increased reactive oxygen species (ROS), which was abolished by the free radical scavengers trolox, 1,10-phenanthroline (phen), and the NAD(P)H oxidase inhibitor diphenylen iodonium (DPI). In contrast, EMFs of 10 mT field strength exerted inhibitory effects on vasculogenesis and chondro-osteogenesis despite robust ROS generation. EMFs of 1 mT and 10 mT increased and decreased vascular endothelial growth factor (VEGF) expression, respectively, which was abolished by DPI and radical scavengers. EMFs activated extracellular-regulated kinase 1/2 (ERK1/2), p38, and c-jun N-terminal kinase (JNK), which was sensitive to DPI treatment. The increase in VEGF by EMFs was inhibited by the ERK1/2 inhibitor U0126 but not by SB203580 and SP600125, which are p38 and JNK inhibitors, respectively, suggesting VEGF regulation by ERK1/2. Chondroosteogenesis and vasculogenesis of ES cells was blunted by trolox, DPI, and the VEGF receptor-2 (flk-1) antagonist SU5614. In mouse fetuses 1 mT EMFs increased and 10 mT EMFs decreased bone mineralization, which was abolished in the presence of trolox. Hence, EMFs induced chondro-osteogenesis and vasculogenesis in ES cells and bone mineralization of mouse fetuses by a ROS-dependent up-regulation of VEGF expression.