機車廢氣對雄性大鼠之生殖毒性

Abstract

機車廢氣(motorcycle exhaust，ME)在台灣都市中為一主要空氣污染源，其對人體健康造成潛在危害。機車廢氣中含有許多有毒化學物質如：benzene和benzo(a)pyrene。Cytochrome P450為一相(phase I)代謝酵素，在體內主要負責藥物、致癌物、荷爾蒙和環境污染物的代謝。目前研究指出，模擬人們暴露機車廢氣之情況，雄性大鼠暴露二行程機車廢氣四週，在雄性大鼠可明顯地降低睪丸與副睪尾精子密度，在副睪尾與輸精管的精子活動力亦有明顯的下降。在與雌性大鼠的交配實驗中，暴露機車廢氣組與雌性大鼠的交配率、懷孕率和著床率皆有顯著下降，並且增加早期死胎比率。但每胎仔鼠數目則無太大差異。ME並且可使副睪組織中total glutathione含量下降。病理切片之結果顯示暴露ME後，睪丸之細精管有萎縮現象和副睪細胞壞死。萘 ( naphthalene) 為ME中之主要多環芳香烴，以萘 275 mg/kg 處理雄性大鼠四天，可增加副睪中androgen receptor interacting protein 3 基因表現。四行程機車廢氣增加每天暴露時間為四小時，睪丸與副睪之組織重量與精子數目皆有下降現象。利用抗氧化劑，vitamin E (50 mg/kg)，處理暴露二行程機車廢氣之雄性大鼠，結果顯示共同處理組之睪丸與副睪尾精子密度下降相較ME組有恢復的現象。睪丸與副睪尾的聚合酶連鎖反應(RT-PCR)分析基因表現，發炎相關基因IL-6、IL-1α、IL-1β和COX-2在共同處理組皆有回復ME組誘導基因表現上升的趨勢。暴露二行程機車廢氣之雄性大鼠的交配率和懷孕率的結果更加支持暴露ME造成精子毒性的病理切片和基因表現的結果。本研究首次證明了機動車輛排廢物對交配率和懷孕率的不良影響。總結以上，目前研究以證明了機車廢氣造成雄性大鼠的生殖毒性，氧化壓力可能為其主要機制之一。此結果將有益於我們對於機車廢氣的危害評估。

Motorcycle exhaust (ME) is a major source of air pollution in the urban areas and a potential health hazard in Taiwan. ME contains carcinogenic benzene and benzo(a)pyrene and many toxic chemicals. Cytochrome P450 is the primary enzyme system responsible for the metabolism of drugs, carcinogens, steroid hormones, and environmental pollutants. The present studies showed that inhalation exposure of male rats to ME at environmental realistic conditions for 4 weeks decreased testis and epididymis weights, testis and cauda epididymis sperm concentrations, and cauda epididymis and vas deferens sperm mobility. The results of reproductive study showed that 2-Stroke ME inhalation exposure of male rats produced decreases in male mating index, female fecundity index, implantation site and an increase in pre-implantation loss. Litter size from the ME group was smaller than the controls. ME inhalation decreased epididymal glutathione content. The result of histological analysis showed ME produced testicular atrophy and epididymal tubule necrosis. Treatment of rats with 275 mg/kg naphthalene, a major polycyclic aromatic hydrocarbon component of ME, intraperitoneally once daily for 4 day, increased androgen receptor interacting protein 3 mRNA expression in cauda epididymis, analyzed by RT-PCR. Inhalation exposure to 1:10 diluted 4-stroke ME for 4 weeks resulted in decreases of testis and epididymis weights, testicular and cauda epidiymal sperm contents. Cotreatment with 2-stroke ME inhalation exposure and 50 mg/kg vitamin E, an antioxidant, orally for 4 weeks reduced ME-mediated decreases of testis and epidiymis weights and sperm density. The vitamin E cotreatment blocked at least partly induction of IL-6 mRNA expression by ME, analyzed by real-time RT-PCR. Similar trends of protective effects by the antioxidant were observed with IL-1α, IL-1β, and COX-2 mRNA. These fertility and gestational data were supportive of the morphology and gene expression data showing that ME inhalation exposure produced spermatotoxic and reproductive effects in male rats. To the best of our knowledge, this is the first to show adverse effects on mating and fertility from exposure to emissions from motor vehicles. In summary, the present findings show that ME inhalation has the ability to cause reproductive toxicity in male rats and the underlying mechanisms involve oxidative stress. These results may help to assess the health risk associated with ME exposure.