Co-Investigator(Kenkyū-buntansha) |
SATO Eimei Tohoku University, Graduate School of Agriculture, Professor, 農学研究科, 教授 (80093243)
NIWA Koji Okayama University, Department of Agriculture, Professor, 農学部, 教授 (40089115)
MANABE Noboru Kyoto University, Graduate School of Agriculture, Associate Professor, 農学研究科, 助教授 (80243070)
KASAI Magosaburo Kohchi University, Department of Agriculture, Professor, 農学部, 教授 (60152617)
OGURA Atuo National Institute of Infections Deseases, Unit of Veterinary Science, Chief, 獣医科学部, 室長 (20194524)
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Research Abstract |
In the present investigation, we developed a novel assessment method for reproductive and genetic toxicity and teratogenicity of environmental endocrine disrupters (EDs) in farm animals using structural biological techniques, i.e. three dimensional and functional in vivo nuclear magnetic resonance (NMR) observation techniques. (1) In vivo assessment : the novel in vivo ^<31>P-and ^1H-NMR spectoroscopy and ^<31>P-and ^1H-NMR imaging techniques for accurate and noninvasive assessment of teratogenicity induced by EDs were applied. Mice with pregnancy were administered EDs (estradiol 17beta as natural estrogen, diethylstilbestrol, synthetic estrogen, used as positive control reagent, bisphenol A, phyto estrogens, and so on) at extremely low dose (0.001-1,000 ng/kg of body weight), and then in vivo ^<31>P-NMR spectra of embryos were acquired noninvasively and quantitatively to evaluate the energy metabolism (^<31>P-ATP). A significant decrease in embryo ATP level was seen, but no significant toxicological changes were detected by conventional histological and biochemical methods. Thus, in vivo NMR techniques are highly sensitive (at least 1,000-fold more sensitive than conventional methods) and are useful for toxicological assessment of EDs and many environmental pollutants. (2) In vitro assessment : Cultured oocytes, sperm, fertilized eggs and embryos were used to assess the reproductive and genetic toxicity of EDs and environmental pollutants. DNA arkylation, abnormalities of steroid hormone receptor mRNA expression were visualized by noninvasive-real time imaging techniques using a confocal laser microscopy.
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