Transgenerational teratogenesis by prenatal exposure to environmental chemicals in mice

小鼠产前暴露于环境化学物质导致的跨代致畸

• 批准号: 22510078
• 负责人: NAGAO Tetsuji
• 金额: $ 1.33万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22510078/
• 关键词: 合成エストロゲン; 催奇形性; 継世代影響; エピジェネティクス; Ｄｎｍｔ; ＤＮＡメチル化; Dnmt; DNAメチル化; 精巣毒性; エピジェネティックス; DNAメチル化酵素

We demonstrated the increased incidence of congenital defects in the offspring of male mice exposed in utero to synthetic estrogens and that the induction of malformations by the estrogens showed a clear threshold effect. Since estrogens have been reported to be non-genotoxic, epigenetic mechanisms may be involved in the transgenerational teratogenesis by estrogen. The expression patterns of Dnmts mRNA, global DNA methylation levels in testicular cells of embryos exposed to estrogen drugs or in sperm of mature male mice exposed prenatally to estrogen drugs were different from those in the controls. These results support that, when evaluating the toxicities of environmental chemicals, epigenetic effects such as DNA methylation should be taken into account.

我们证明了在子宫内暴露于合成雌激素的雄性小鼠的后代中先天性缺陷的发生率增加，并且由雌激素诱导的畸形表现出明显的阈值效应。由于雌激素无遗传毒性，雌激素的跨代致畸作用可能与表观遗传机制有关。雌激素药物暴露小鼠胚胎睾丸细胞和产前暴露雄性小鼠精子中Dnmts mRNA的表达模式、DNA甲基化水平均与对照组不同。这些结果支持，在评估环境化学品的毒性时，应考虑表观遗传效应，如DNA甲基化。

项目成果

合成エストロゲン剤のマウス胎盤傷害性と胚致死作用

合成雌激素的小鼠胎盘毒性和胚胎致死率

• 发表时间: 2012
• 作者: 長尾哲二;加川 尚;斎藤義明;駒田致和
• 通讯作者: 駒田致和

Maternal bisphenol A oral dosing relates to the acceleration of neurogenesis in the developing neocortex of mouse fetuses

• DOI: 10.1016/j.tox.2012.02.013
• 发表时间: 2012-05-16
• 期刊: TOXICOLOGY
• 影响因子: 4.5
• 作者: Komada, Munekazu;Asai, Yasuko;Nagao, Tetsuji
• 通讯作者: Nagao, Tetsuji

Developmental effects of oral exposure to diethylstilbestrol on mouse placenta

• DOI: 10.1002/jat.2766
• 发表时间: 2013-11-01
• 期刊: JOURNAL OF APPLIED TOXICOLOGY
• 影响因子: 3.3
• 作者: Nagao, Tetsuji;Kagawa, Nao;Komada, Munekazu
• 通讯作者: Komada, Munekazu

Newly developed mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants

新开发的小鼠新生儿行为测试方法评估环境毒物神经毒性风险

• DOI: 10.1002/jat.2802
• 发表时间: 2012
• 期刊: J Appl Toxicol
• 影响因子: 3.3
• 作者: Nagao T;Komada M;Kagawa N
• 通讯作者: Kagawa N

胎児期4-ヒドロキシタモキシフェン曝露はマウス大脳皮質形成を障害する

产前 4-羟基他莫昔芬暴露损害小鼠大脑皮层形成

• 发表时间: 2012
• 作者: 溝端 彩;森佳奈美;駒田致和;長尾哲二
• 通讯作者: 長尾哲二