Research concerning Effects of Endocrine Disrupters on Development of Cleft Lip and/or Palate

关于内分泌干扰物对唇裂和/或腭裂发展影响的研究

• 批准号: 18592209
• 负责人: NIIMI Teruyuki
• 金额: $ 1.58万
• 依托单位: Aichi Gakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592209/
• 关键词: Bisphenol A; Cleft Lip; Congenital Abnormality; Prevention; Thymus Gland

We have elucidated that estradiol, which is estrogen, and bisphenol A (BPA), which is endocrine disrupters, inhibit development of cleft lip and palate in A/J mouse strain, which spontaneously develop cleft lip and palate, and that their inhibitory actions describe an inverted U dose-characteristic curve.1. Correlation between an estrogen receptor and retinoic acid receptor (RAR), which are deeply involved in a process of bone differentiation from mesenchymal stem cells, was studied in order to know mechanism of a BPA action of inhibiting cleft lip and/or palate development.(1) In a study about an effect of BPA on development of RAR using osteoblastic MC3T3-E1 cells, BPA at a concentration of 10-10M and 10-5M had no effect on RAR development.(2) BPA elevated the mRAN level of osteopontin, which is a target gene of RAR, and the action of BPA became the maximum at a concentration of 10-8M shown in an inverted U dose-characteristic curve. The result showed that the action of BPA may possibly be involved deeply in a signal through RAR.2. In order to study correlation between BPA and a RAR ligand, and further, in order to aim at developing a preventive medicine for cleft lip and for palate, 95 kinds of galenicals with 70% ethanol extraction were examined fix finding a RAR ligand to replace an all-trans retinoic acid, which is also a RAR ligand but has a strong action and various side effects.(1) Atractylodinol was identified as a RAR α ligand from Atractylis Rhizoma(2) Eugenol and isoeugenol were isolated and identified from clove.

我们已经阐明，雌二醇，这是雌激素，双酚A（BPA），这是内分泌干扰物，抑制唇腭裂的发展，在A/J小鼠品系，自发发展唇腭裂，他们的抑制作用描述了一个倒U型剂量特征曲线。为了了解BPA抑制唇腭裂发育的作用机制，研究了雌激素受体和视黄酸受体（RAR）之间的相关性，所述雌激素受体和视黄酸受体与间充质干细胞的骨分化过程密切相关。(1)在使用成骨细胞MC 3 T3-E1进行的关于BPA对RAR发育的影响的研究中，浓度为10- 10 M和10- 5 M的BPA对RAR发育没有影响。(2)BPA提高了RAR的靶基因骨桥蛋白的mRAN水平，BPA的作用在10- 8 M浓度时达到最大，如倒U型剂量特征曲线所示。结果表明，BPA的作用可能通过RAR深入参与一个信号.为了研究BPA和RAR配体之间的相关性，并且进一步地，为了旨在开发唇腭裂的预防药物，检查了95种具有70%乙醇提取物的草药，以寻找RAR配体来代替全反式视黄酸，全反式视黄酸也是RAR配体，但是具有强作用和各种副作用。(1)从白术中分离鉴定了丁香酚和异丁香酚。