Non-invasive assessment for teratogenic-toxicity of environmental disrupters by structural- and cel lurar-biological methods

通过结构生物学和细胞生物学方法对环境破坏物的致畸毒性进行非侵入性评估

• 批准号: 11556052
• 负责人: MANABE Noboru
• 金额: $ 8.64万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11556052/
• 关键词: environmental distruptors; reproductive toxicity; genetic toxicity; food chain; embryionic teratogenecity; reproductive physiology; genital gland; structural biology; 生体核磁気共鳴装置; 外因性内分泌攪乱物質; ステロイドホルモン; オーファン受容体; ステロイドホルモン受容体; 哺乳類生殖子; 哺乳類胎児

To develope non-invasive and real-time assesment technique for teratogenic activity of environmental disruptors (Eds), so called environmental hormones, we made a novel appl ication for nuclear magnetic resonance (NMR) microscopy to quantitatively observe of malmorphogenecity in mammal ian embryos. By using the new structural-biological equipment, that is magnetic resonance (NMR)-imaging appliance, developmental disorder inmammaIianembryos induced byoral maternal-administration of some Eds was non-invasiveIy detected. This MRI methods with an enhanced spatial resolution due to the use of a high static magnetic field and high magnetic field gradients. The NMR appl iance is a useful tool for non-invasive, real-time and continuous examination of tissue and organs at the histological level (minimum 50 micron cubic). We demonstrated that many Eds induced widespread malformation in developing mammal ian embryos, and that two-dimensional and/or three-dimensional NMR micro-images demonstrated defects in skeleton and soft tissue similarly to conventional histopathological assessments. Although further improvements are required for rapid dynamic imaging of living embryos in the peritoneal cavity of mother with Eds administration, our NMR-imaging technique will provide new approach as for multi-parametric assessment of embryo development under both physiological and pathological conditions.

为了开发环境破坏者（EDS）（EDS）的非侵入性和实时评估技术，所谓的环境激素，我们为核磁共振（NMR）显微镜做出了一种新颖的应用，以定量地观察到哺乳动物Ian胚胎中的不肾脏生殖。通过使用新的结构生物学设备，即磁共振（NMR）图像，发育障碍Inmammaiianembryos诱导了某些EDS的综合母体管理，未检测到。由于使用高静态磁场和高磁场梯度，该MRI方法具有增强的空间分辨率。 NMR Appl IANCE是在组织学水平（最低50 micron立方）对组织和器官进行非侵入性，实时和连续检查的有用工具。我们证明，许多ED在发展哺乳动物IAN胚胎中引起了广泛的畸形，并且二维和/或三维NMR微图像在骨骼和软组织中与常规组织病理学评估相似地显示出缺陷。尽管需要进一步的改进，以便在母亲的腹膜腔中快速动态成像进行EDS给药的腹膜腔，但我们的NMR成像技术将为生理和病理条件下的胚胎发育的多参数评估提供新的方法。

项目成果

Mizuho Nakayama,Noboru Manabe,Hajime Miyamoto et al.: "Species specific differences in apoptotic cell localization in granulosa and theca interna cells during follicular atresia in porcine and bovine ovaries."Journal of Reproduction and Development. 46・2.

Mizuho Nakayama、Noboru Manabe、Hajime Miyamoto 等人：“猪和牛卵巢卵泡闭锁期间颗粒细胞和卵泡膜内细胞凋亡细胞定位的物种特异性差异。”生殖与发育杂志 46・2。

Noboru Manabe et al.: "In vivo noninvasive nuclear magnetic resonance (NMR) technique for assessment of teratogenicity induced by chemicals"Chemical Engineering. 47-2. 110-114 (2002)

Noboru Manabe 等人：“用于评估化学品引起的致畸性的体内无创核磁共振（NMR）技术”化学工程。

Kozue Yamada-Uchio, Noboru Manabe et al.: "Abnormalities of extracellular matrix metabolisms in the kidney of ICGN mice, a strain of mice with hereditary nephrotic syndrome. In : Miyamoto H, Manabe N (eds), Reproductive Biotechnology : Reproductive biotec

Kozue Yamada-Uchio、Noboru Manabe 等人：“ICGN 小鼠（一种患有遗传性肾病综合征的小鼠品系）肾脏细胞外基质代谢异常。见：Miyamoto H、Manabe N（编辑），生殖生物技术：生殖生物技术

Naoko Inoue, Noboru Manabe et al.: "Elongation of cell cycle of early stage tetraploid murine embryos induced by cytochalasin B"Japanese Journal of Embryo Transfer. 23. 44-51 (2001)

Naoko Inoue、Noboru Manabe 等人：“细胞松弛素 B 诱导的早期四倍体小鼠胚胎细胞周期的延长”日本胚胎移植杂志。

Miki Sugimoto, Noboru Manabe et al.: "Uilization of NMR microscopy in developmental toxicology : assessment of mouse embryo malformations induced by maternal administration of retinoic acid. In: Miyamoto H, Manabe N (eds), Reproductive Biotechnology : Rep

Miki Sugimoto、Noboru Manabe 等人：“NMR 显微镜在发育毒理学中的应用：评估母体施用视黄酸诱导的小鼠胚胎畸形。见：Miyamoto H、Manabe N（编辑），生殖生物技术：Rep