Changes in miRNAs expression profiling in testis of mice exposure to Sulfur Dioxide and Fluoride
首发时间:2012-12-20
Abstract:MicroRNAs (miRNAs) are believed to play important roles in developmental and other cellular processes by hybridizing to complementary target mRNA transcripts, also involved in the development of mammalian spermatogenesis. Fluoride and sulfur dioxide are two well known environment pollutants, which present a serious threat to male reproduction. To compare the global miRNA expression profiling and regulation pattern in mouse testes between normal mouse and F or SO2-treat mice by using miRNA microarray technology, 144 male Kunming mice were divided randomly into four groups of thirty-six mice each. One group was left untreated as controls, and the other three groups were administered, respectively, for thirteen consecutive weeks, 150 mg NaF/L (45 mg F-/L) in their drinking water, SO2 in ambient air (26.2 mg/m3 SO2, 3hr/day), or were exposed to both NaF and SO2 together. After 15 weeks, testis totals RNA of the mouse model were gathered for miRNA microarray study. Simultaneity, reproductive capacity of mice, DNA contents distribution in testis cells, and bcl-2, bax, and p53 genes mRNA expression were detected to interpret the changed miRNA expression profiles. The results exhibited that MiR-106a in the NaF group, miR-449a, miR-16, miR-15b, and miR-34c in the SO2 groups, and miR-204 and miR-34a in the NaF+SO2 group were un-regulated significantly in testes of mice, compared with the controls, respectively. Whereas miR-34a decreased by 3.3-fold in the SO2 group, and miR-34b was down-regulated by more than 1.5-fold in the NaF+SO2 group. Further investigation indicates that predicted pathways according to significant miRNA are primary related to cell cycle, apoptosis, and MAPK signal pathway. Furthermore, the development of testis and reproductive capacity of male mouse have been weakened by F or SO2, especially, by F and SO2 together treatment. FCM analysis show that the percents of apoptosis cells in testis were increased significantly in experiment groups, DNA contents distributions have been disturbed by F or SO2. Expression of p53 and bcl-2 mRNA decreased, and bax gene was increased by1.87, 2.40 and 2.89 times as high as those in the control groups by QRT-PCR. However, both F or SO2 and the combination heighten the ratios of p53/bcl-2 and bax/bcl-2, all these changes lead to a common result of the spermatogenic cell apoptosis. In conclusion, changed miRNAs expression regulation should be look as the main mechanism of depressed male reproduction function of mouse induced by F or SO2 or their combination. This is the first miRNA microarray study to focus on evaluating altered miRNA expression profiles in testis of mice exposure to F or SO2. The miRNA microarray and bioinformatics analysis is a fast, high-throughout, exacts, foreground technique contribute toward elucidating the function of miRNAs in normal and impaired male reproduction by environment factors.
keywords: Fluoride and sulfur dioxide Male mice miRNAs expression profile Testis
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氟和二氧化硫对小鼠睾丸组织MiRNA表达谱的影响
摘要:氟和SO2为作为世界公认的两种环境主要污染物,在许多地区共同存在,且倾向于产生联合毒性作用,对动物及人的健康危害十分严重。为了探讨二者的雄性生殖毒性作用机理,本研究建立了氟(150mg/L NaF)和SO2(26.2 mg/m3,3hr/day)小鼠动态染毒模型,采用miRNA表达谱芯片、流式细胞术(FCM)、免疫组化、Real-time PCR等技术手段,对氟和SO2引起的雄性小鼠睾丸组织miRNA表达水平及相关靶基因和涉及信号通路进行了一系列研究探索。结果发现二者可引起小鼠睾丸组织中相关miRNA表达水平发生改变,通过生物信息学分析和相关验证试验证实了其在生殖功能损伤中的调节作用。
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