权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies on diesel exhaust on male reproductive system and its endocrine disrupting action

柴油机尾气对男性生殖系统及其内分泌干扰作用的研究

基本信息

批准号：
12470511
负责人：
TAKEDA Ken
金额：
$ 8.96万
依托单位：
Tokyo University of Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

We investigated the effect of exposure of pregnant mice to diesel exhaust on male gonad development at the level of mRNA expression. Expression of mRNAs for steroidogenic factor-1 (Ad4BP/SF-1) and Mullerian inhibitory substance (MIS), which are essential for male gonadal differentiation, decreased significantly in male fetuses when maternal mice were exposed to diesel exhaust at levels of 0.1 mg and 3.0 mg diesel exhaust particles (DEP)/m^3 for 8 hours per day between days 2 and 13 post coitum. Expression levels of mRNAs for steroidogenic cytochrome P450 genes regulated by Ad4BP/SF-1, especially 3β-hydroxysteroid dehydrogenase (3β-HSD) and aromatase, were also decreased by exposure to diesel exhaust. There were no significant differences in levels of estrogen receptor (ER) and androgen receptor (AR) mRNAs between control and exposed mice. The data indicate that exposure of pregnant mice to diesel exhaust affects the expression of genes essential in the early stages of embryonic development.The effects of in utero exposure to diesel exhaust (DE) on the mouse malereproductive system after birth was examined. Various markers that appear in pups were assessed. Pregnant ICR mice inhaled DE at DEP concentrations of 0.3,1.0,or 3.0 mg DEP/m3 or clean air, as the control, on days 2-16 days post coitum. On postnatal day (PND) 28, the weight of the testes and accessory glands, and testosterone concentration in serum were significantly higher in the DE-exposed male pups. Testosterone concentration correlated significantly (P<0.01) with the expression of steroidogenic enzyme mRNAs, weight of the testes and male reproductive accessory glands, and daily sperm production. These findings indicate that very early stage mouse embryo exposure to DE leads to endocrine disruption after birth.

我们研究了妊娠小鼠暴露于柴油机尾气对雄性性腺发育的影响，在mRNA表达水平。当母鼠暴露于0.1 mg和3.0 mg/m^3柴油机排气颗粒（DEP）水平的柴油机排气中8 h/d时，雄鼠胚胎中类固醇生成因子-1（Ad 4 BP/SF-1）和苗勒管抑制物质（MIS）的mRNA表达显著降低。受Ad 4 BP/SF-1调控的类固醇生成细胞色素P450基因的mRNA表达水平也受到柴油机尾气的影响，尤其是3β-羟基类固醇脱氢酶（3β-HSD）和芳香化酶。雌激素受体（ER）和雄激素受体（AR）mRNA水平在对照组和暴露组小鼠之间无显著差异。结果表明，妊娠小鼠暴露于柴油机尾气中，影响胚胎发育早期必需基因的表达，并观察了宫内暴露于柴油机尾气（DE）对小鼠出生后雄性生殖系统的影响。评估了幼仔中出现的各种标志物。ICR孕鼠于妊娠后2-16天吸入DEP浓度为0.3、1.0、3.0 mg DEP/m3的DE或清洁空气作为对照。在出生后第28天（PND），睾丸和附腺的重量，血清中的睾酮浓度显着较高的DE暴露的雄性幼崽。睾酮浓度与睾丸激素生成酶mRNA的表达、睾丸和雄性生殖附腺的重量以及每日精子产量呈显著正相关（P<0.01）。这些发现表明，非常早期的小鼠胚胎暴露于DE导致出生后的内分泌干扰。