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

本研究从基因表达水平探讨了柴油尾气暴露对孕鼠雄性性腺发育的影响。在孕鼠出生后第2~13天，每天暴露于0.1 mg和3.0 mg柴油尾气(DEP)浓度为0.1 mg/m^3和3.0 mg/m^3的柴油尾气中，雄性胎鼠性腺分化所必需的类固醇生成因子-1(Ad4BP/SF-1)和苗勒氏抑制物质(MIS)的mRNAs表达显著降低。受Ad4BP/SF-1调控的促类固醇细胞色素P450基因的mRNAs表达水平也受到柴油尾气的影响，尤其是3-羟基类固醇脱氢酶(3-β-β-HSD)和芳香化酶的表达水平降低。对照组和染毒组小鼠雌激素受体(ER)和雄激素受体(AR)mRNAs水平无显著差异。研究结果表明，孕鼠暴露于柴油尾气中会影响胚胎发育早期必需基因的表达。对出现在幼崽身上的各种标记进行了评估。妊娠ICR小鼠在孕后第2~16天分别吸入0.3、1.0、3.0 mg DEP/m~3的DE或清洁空气作为对照。出生后第28天，暴露于DE的雄性幼鼠的睾丸和附腺重量及血清睾酮浓度显著高于对照组。睾酮浓度与类固醇合成酶mRNAs的表达、睾丸和雄性生殖附腺的重量以及每日的精子产量显著相关(P&lt；0.01)。这些发现表明，非常早期的小鼠胚胎暴露于DE会导致出生后内分泌中断。

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.