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1.
Many studies have focused on environmental estrogen-related diseases. However, no consistent gene markers or signatures for estrogenicity have been discovered in mammals. This study investigated the estrogenic effects of 17β-estradiol on the prostate in immature male mice. Consistent U-shaped responses were seen in bodyweight, ventral prostate epithelial morphology, and miRNA expression levels. Specifically, most estradiol regulated miRNAs were downregulated at low doses of estradiol (0.2 and 2 mg·kg–1), and whose expression returned to the control level at a larger dose (200 mg·kg–1). The function of these regulated miRNAs is related to the prostate cancer and PI3K-Akt signaling pathways, which is consistent with the function of estradiol. Furthermore, the miRNA-processing machinery, Drosha, in the prostate was also regulated in a similar pattern, which could be a part of the U-shaped miRNA expression mechanism. All of these data indicate that the prostate is a reliable organ for evaluating estrogenic activity and that the typical nonmonotonic dose-response relationship could be used as a novel biomarker for estrogenicity.
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为探讨PFOS胚胎期及哺乳期暴露对动物子代学习记忆能力影响的分子机理,采用微小RNA(miRNA)芯片技术检测PFOS胚胎期及哺乳期暴露对出生第1和7天大鼠脑组织miRNA表达的影响,分析突触可塑性相关miRNA表达的差异变化。结果显示,经PFOS暴露后出生第1和7天的大鼠脑组织中分别有24和17个miRNA发生显著性差异表达(p<0.05),其中与突触传递和神经递质转运等相关的miRNA的差异表达最为显著,主要包括miR-466b、miR-672、miR-297、miR-674-3p和miR-207。差异表达miRNA的路径分析显示出生后1和7d的大鼠的长时程增强效应(LTP)均受PFOS显著影响(p<0.05),这说明PFOS胚胎期及哺乳期暴露可能通过影响LTP的形成、发展和维持过程对大鼠子代大脑学习记忆能力造成威胁,并且miR-466b、miR-672、miR-297、miR-674-3p和miR-207可能参与了其中的调控过程。  相似文献   

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microRNAs作为临床疾病早期诊断的新型生物标记物越来越受到重视,为了进一步探究其在大气污染暴露后引起疾病的分子染毒机制。本研究通过建立大气污染小鼠染毒模型,利用Agilent芯片筛查小鼠肺组织中microRNAs差异表达谱,并通过实时荧光定量PCR方法验证芯片结果,使用Target Scan,PITA,microRNAorg数据对差异mi RNA进行靶基因预测,进行靶基因富集的基因功能(GO)和信号通路(KEGG)分析。结果显示,大气细颗粒物暴露2周后小鼠肺组织microRNAs有显著差异表达谱,高剂量暴露组与对照组比较有4个mi RNAs上调,低剂量暴露组与对照组比较有2个mi RNAs上调,高剂量组与低剂量组比较,有4个mi RNAs上调(标准为fold change值=2.0且P值=0.05),挑选差异明显的mi RNAs进行q RT-PCR验证,mi R-139-5p、mi R-691及mi R-340-3p变化趋势与芯片一致,生物信息学结果显示,差异表达的mi RNAs所调控的靶基因明显富集于34个GO通路(包括RNA转录酶II启动子的转录,RNA拼接,DNA模板,蛋白质结合和核酸结合)和32个KEGG通路(主要集中轴突导向通路和癌症通路)。综上所述,大气细颗粒物暴露染毒可诱导小鼠肺组织中mi R-139-5p、mi R-691及mi R-340-3p明显上调,且生物信息学分析提示中枢神经系统发育及癌症通路可能作为PM2.5暴露相关差异表达mi RNAs调控靶基因介导的主要致病通路。  相似文献   

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多氯联苯对孔雀鱼卵黄蛋白原的诱导及检测   总被引:3,自引:0,他引:3  
为探讨利用孔雀鱼(Poecilia reticulata)卵黄蛋白原(Vitellogenin,Vtg)作为生物标志物检测环境雌激素的可行性,采用浸浴法分别使用17β-雌二醇(E2)和多氯联苯(PCBs)对雄性孔雀鱼成鱼进行染毒,30d后测定其性腺系数(GSI)和肝指数(LSI),并将鱼体整体匀浆进行常规聚丙烯酰胺凝胶电泳(Native-PAGE)及磷、脂和糖蛋白特异染色分析.结果表明,PCBs对雄性孔雀鱼具有雌激素效应,和E2均可以诱导雄性孔雀鱼体内产生Vtg,但诱导组雄鱼GSI及LSI与对照组比较均无显著性差异(p>0.05).Native-PAGE及磷、脂、糖蛋白特异性分析表明,孔雀鱼Vtg是一种富含磷、脂、糖的蛋白,具有VtgⅠ、VtgⅡ和VtgⅢ等3种形式,其分子量分别为642kDa、541kDa和441kDa.雄性孔雀鱼Vtg可作为环境雌激素监测的有效生物标记物.  相似文献   

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为探讨利用雄性唐鱼(Tanichthys albonubes)卵黄蛋白原(Vitellogenin,Vtg)作为生物标志物检测环境雌激素的可行性,采用浸浴法用50μg·L-117β-雌二醇(E2)对雄性唐鱼进行染毒,30d后将鱼体整体匀浆进行常规聚丙烯酰胺凝胶电泳(Native-PAGE)以分析Vtg的产生;并采用Mg2+-EDTA选择性沉淀和Q Sepharose阴离子交换层析对Vtg进行分离纯化.结果表明,E2诱导下,雄性唐鱼产生了雌性特异蛋白Vtg,并且可在体内积累;利用Mg2+-EDTA选择性沉淀和Q Sepharose阴离子交换层析的两步纯化方法可分离纯化唐鱼整体匀浆Vtg;经Native-PAGE鉴定,确定唐鱼Vtg的分子量为440kDa.以上结果提示,雄性唐鱼Vtg可以作为环境雌激素监测的有效生物学标记物。  相似文献   

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内分泌干扰物莠去津对鲫鱼血清激素的影响   总被引:3,自引:1,他引:3  
为了研究低剂量条件下,内分泌干扰物莠去津对鲫鱼血清激素的影响,探讨其作用机理和剂量-效应关系,同时筛选出敏感的生物标志物,实验以除草剂莠去津对鲫鱼进行低剂量染毒(染毒浓度0~3mg·L-1),采用放射免疫法测定莠去津长期暴露下(60d)幼年雄性鲫鱼血清中性激素(17β-雌二醇(E2)、睾酮(T))及甲状腺激素(促甲状腺激素(TSH)、三碘甲状腺原氨酸(T3))的浓度,并将测定结果与空白对照及溶剂对照进行比较.结果发现:1)莠去津长期暴露下,各处理组鲫鱼血清E2浓度普遍升高,0.023、0.094、1.500、3.000mg·L-1组与空白对照相比,升高显著(p<0.05);2)各处理组鲫鱼血清T浓度与空白对照相比均无显著性差异(p>0.05);3)莠去津长期暴露下,低浓度莠去津组(0.006、0.023mg·L-1组)鲫鱼血清TSH浓度与空白对照相比差异不显著(p>0.05),而高浓度莠去津组(0.094、1.500、3.000mg·L-1组)则显著降低(p<0.05);4)类似地,莠去津长期暴露下,低浓度莠去津组(0.006、0.023、0.094、0.375、1.500mg·L-1组)鲫鱼血清T3浓度与空白对照相比差异不显著(p>0.05),只有高浓度莠去津组(3.000mg·L-1组)显著升高(p<0.05).实验结果表明,低剂量长期暴露下,莠去津对鲫鱼体内性激素及甲状腺激素具有一定的干扰作用,尤其是对17β-雌二醇影响更为显著,因此,17β-雌二醇可作为评价农药内分泌干扰效应的生物标志物.  相似文献   

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Regeneration is a vital physiological process for survival of adult organisms. Bisphenol A (BPA), diethystilbestrol (DES), 17α-ethinylestradiol (EE2), and 17β-estradiol (E2) were examined for their effects on head formation in decapitated freshwater planarians (Dugesia japonica). The median lethal concentration of the test chemicals and the median inhibitory concentration for decapitated planarians and different regenerative endpoints, were determined for 3–7 d of exposure. For planarian head regeneration, the no-observed-effect level of BPA and DES was 0.05 mg L?1 and 1 mg L?1 for EE2 and E2. The effects of BPA, DES, and EE2 on asexual planarian regeneration did not correspond with the order of their estrogenic potencies, suggesting that the effects, at least partially, were due to general toxicity rather than their estrogenicity. In view of the published data on concentrations of xenoestrogens in water bodies versus the nominal levels tested here, this study suggests that the current environmental levels of BPA, DES, EE2, and E2 have no immediate adverse effects on freshwater planarian regeneration.  相似文献   

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Background Ecotoxicology utilizes alterations of biological parameters of organisms as biomarkers of toxic exposure or effects. In environmental monitoring, biomarkers function as sensitive indicators of chemical pollution or as early warning signal of late effects Aim The pre-requisite for using a biological parameter as biomarker is the ability to unequivocally distinguish between the natural or normal and the induced or abnormal expression of the marker. This article discusses problems in discriminating between the normal and induce state, using morphological biomarkers as an example. Results and Discussion Morphological and/or anatomical parameters are intuitively considered to be rather invariable. This article shows for the example of gonad morphology of fish that this expectation is not always correct, but that morphological markers may display pronounced baseline variability. The reasons for this variability are often not understood. This is limiting the utility and interpretation of the biomarker response, in particular when organisms are not only exposed to chemical but to multiple stressors. Outlook The problem of discriminating between natural and induced variability of biomarkers is of particular relevance in low dose exposure scenarios, when stressors other than toxic chemicals may confound the toxicant-induced changes of the biomarker status. To better handle this problem and to be able to distinguish between adaptive and adverse changes, ecotoxicology has to set out for improved understanding of the phenotypic plasticity of organisms and genotypes,  相似文献   

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3-Dehydroquinic acid dehydrase/shikimate dehydrogenase (DHD/SDH) is the only bifunctional enzyme in the shikimic acid pathway. It can catalyze the generation of shikimic acid and gallic acid. To investigate the expression and regulation patterns of DHD/SDH in tea, we aimed to determine (1) the miRNA-mediated cleavage of DHD/SDH involved in the shikimic acid pathway, (2) the expression pattern of miRNA and their targets, and (3) the expression pattern of three DHD/SDH genes in tea plant (Camellia sinensis) with different hormone treatments via online prediction, RLM-RACE, and qPCR. Based on the miRNAs obtained, we identified four miRNAs that regulated CsDHD/SDH in tea. CsDHD/SDH2 was targeted by miR5180b, miR1510b-5p, and miR24; CsDHD/SDH3 was targeted by miR868-5p. We also found that CsDHD/SDH2 and CsDHD/SDH3 have a similar expression pattern under different hormone treatments, and they were synergistic with each other. CsDHD/SDH1 exhibited an expression pattern opposite to that of the other two homologues, and increased expression of CsDHD/SDH1 reduced the expression of the other two genes. © 2018 Science Press. All rights reserved.  相似文献   

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Both the UK and Japan are densely populated islands with relatively short rivers. Therefore, both countries are likely to be highly exposed to contaminants emanating from their human populations. This review considered how effective the different sewage treatment facilities of the two countries are at removing steroid estrogens from the effluent. The methods of estrogen analysis in sewage effluent, the number and importance of different sewage treatment types, and their apparent effectiveness at removing estrogens were all considered. In both countries, the activated sludge treatment was dominant in terms of people served and water discharged. The analytical techniques used by those studying estrogen concentrations in effluents in both countries were broadly similar. Activated sludge plant (ASP) effluent in the UK typically contained around 2 ng/L estradiol (E2) and 8 ng/L estrone (E1), while Japanese ASPs typically reported E2 as below detection, and 10 ng/L E1 in their effluents. When estrogenic bioassays were used in Japan, they typically record an estrogenic potency of 10 ng/L E2 equivalents. Even taking into account ethinylestradiol (EE2) (not found in Japanese effluents), the overall estrogenicity of British sewage effluents would appear to be the same as that of Japanese sewage effluents (around 10 ng/L E2 equivalents). This suggests that the ASPs serving the large urban communities in Japan and the UK would have effluent of similar estrogenic potencies. Less information is available about the more numerous biological (trickling) filter plants (BFP) in the UK and oxygen ditches (OD) in Japan which tend to serve smaller, more rural communities. The available data would suggest that the BFPs are significantly less efficient than the ODs at removing E1. This would suggest that in similar circumstances, British headwaters (where this sewage treatment plant (STP) type is often found) might be more at risk from endocrine disruption than their Japanese counterparts. Overall, the apparently higher incidence of endocrine disruption in British wild fish than in Japanese wild fish cannot be attributed to differences in the efficiency of their respective STPs.  相似文献   

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A number of xenobiotic organic substances are known which, in cases of prenatal exposition, may produce an estrogenic effect leading subsequently to serious reproductive disorders in the male progeny. Damage of this kind which is seen to occur in wildlife populations leads to the assumption that environmental chemicals exerting such estrogenic effects may be responsible for these disorders. Listed here are environmental chemicals which are known to date to exert an estrogenic effect. The article provides a review of papers and hypotheses on the estrogenic effects of xenobiotic substances. This is followed by a discussion concerning the significance of chemical estrogenicity on environmental and chemical policies as well as on the possibilities and limitations of test systems for the verification of estrogenicity.  相似文献   

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基于苋菜转录组的ARF基因家族鉴定及表达   总被引:1,自引:0,他引:1  
ARFs(auxin response factors)是重要的生长素响应因子,在植物的生长发育过程中起着关键的作用.基于‘大红’苋菜转录组数据,通过在线分析软件SMART和NCBI-Blastp的注释筛选苋菜ARF基因家族成员(AtrARF);利用生物信息学分析软件,对AtrARFs蛋白的理化性质、二级结构、亚细胞定位、保守氨基酸序列进行预测分析;构建系统进化树,预测可能调控AtrARF的miRNAs.分析AtrARF在蓝光和黑暗处理下苋菜胚轴中,及在不同种类及浓度的生长素处理下苋菜幼苗中的表达水平.分析结果表明,在苋菜中共鉴定得到29个ARF基因,其编码蛋白的长度在80-1 107 aa之间,蛋白分子量约为8.850×103-123.300×103,等电点在4.09-9.92之间.亚细胞定位预测结果均定位于细胞核,有15个保守氨基酸序列;系统进化树显示,29个AtrARF分为3个大组;MiRNA预测结果显示,至少有5个AtrARF家族成员受到miRNA调控.定量结果显示,AtrARFs在蓝光和黑暗、不同种类及浓度的生长素处理下表达模式均不相同.本研究表明AtrARFs受光质和生长素调控,在苋菜生长发育过程中发挥重要作用.(图8表4参34)  相似文献   

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Cadmium (Cd2+), a known carcinogen, mimics the effects of estrogen in the uterus and mammary gland suggesting its possible involvement in the development and progression of breast cancer. This lab showed through analysis of a small set of archival human diagnostic specimens that the third isoform of the classic Cd2+ binding protein metallothionein (MT-3) is not expressed in normal breast tissue, but is expressed in some breast cancers and that expression tends to correlate with a poor disease outcome. The goals of this study were to verify that overexpression of MT-3 in a large set of archival human diagnostic specimens tends to correlate with poor disease outcome and define the mechanism of MT-3 gene regulation in the normal breast epithelial cell. The results showed that MT-3 was expressed in approximately 90% of all breast cancers and was absent in normal breast epithelium. The lack of MT-3 staining in some cancers correlated with a favorable patient outcome. High frequency of MT-3 staining was also found for in situ breast cancer suggesting that MT-3 might be an early biomarker for breast cancer. The study also demonstrated that the MCF-10A cell line, an immortalized, non-tumorigenic model of human breast epithelial cells, displayed no basal expression of MT-3, nor was it induced by Cd2+. Treatment of the MCF-10A cells with the demethylation agent, 5-aza-2′-deoxycytidine, or the histone deacetylase inhibitor, MS-275, restored MT-3 mRNA expression. It was also shown that the MT-3 metal regulatory elements are potentially active binders of protein factors following treatment with these inhibitors suggesting that MT-3 expression may be subject to epigenetic regulation.  相似文献   

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Asoh  K. 《Marine Biology》2003,142(6):1207-1218
The expression of protogyny often differs among populations of a single species. The humbug damselfish, Dascyllus aruanus (Linnaeus), typically lives in spatially discrete groups of several individuals around live coral colonies and has been reported to be protogynous. The size and sexual composition of groups of this species, however, vary with the size of the coral patch or the degree of coral cover. The present study examined gonadal development and sexual pattern in a population of D. aruanus living in continuous coral-cover habitat. Fish were collected in Tumon Bay, Guam (13°31′N; 144°47′E), during a 2-week period in July and August 1996. Reflecting their distributions, small fish (n=54) were collected at depths of 1–2 m over continuous Porites spp. patches, and large fish (n=56) were collected at depths of 2–3 m over a continuous Acropora spp. patch. Gonadal development was examined histologically. Gonads of D. aruanus first developed an ovarian lumen and primary-growth stage oocytes. From this ovarian state or from more developed ovaries with cortical-alveolus stage oocytes, some gonads developed into testes through degeneration of oocytes and development of spermatogenic tissue. Developing spermatogenic tissue only occurred in gonads having pre-cortical alveolus stage oocytes, and the size of individuals with gonads of this type overlapped mainly with the size range of individuals with gonads containing only pre-vitellogenic oocytes (i.e. immature females). This suggested that functional female-to-male sex change was rare or absent in this population of D. aruanus. Moreover, the different habitat distributions of small and large fish suggest that sex determination in immature fish occurs in the absence of adults.  相似文献   

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A preliminary investigation of the solution phase behaviour of the biomarker compound 1-aminopropan-2-one (APR) using NMR spectroscopy was carried out. This was achieved, in part, by synthesis of APR with13C-enrichment in the methylene position. In this paper, we report that this biomarker undergoes H/D exchange with D2O, probably via an enol intermediate. In addition, use of13C-enriched APR enabled its detection by13C NMR spectroscopy at environmentally relevant concentrations.  相似文献   

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酵母双杂交技术构建重组人雌激素受体基因酵母   总被引:10,自引:9,他引:1  
应用酵母双杂交技术构建重组人雌激素受体基因酵母,用以检测类/抗雌激素化合物和环境样品的类/抗雌激素活性.采用多聚酶链反应(PCR)法扩增人雌激素受体(hER)基因,构建诱饵质粒pGBKT7-ER LBD;分别提取并纯化两种含有ER共激活因子基因的靶质粒pGAD424-GRIP1和pGAD424-SRC1;诱饵质粒和靶质粒同时转染酵母细胞Y187,于营养缺陷型培养基(SD/-Trp/-Leu)上筛选阳性菌落,分别构建两种ER双杂交酵母ER+GRIP1和ER+SRC1.考察双杂交酵母与不同激素:17β-雌二醇(E2)、二氢睾酮(DHT)、孕酮(PG)以及三碘甲状腺原氨酸(T3)的结合情况,并考察了雌激素受体拮抗剂4-羟基他莫昔芬(4-OHT)与酵母的相互作用.结果表明:ER+GRIP1和ER+SRC1酵母均能够专一性的和E2结合,并存在显著的剂量-效应关系,E2对ER+GRIP1和ER+SRC1酵母β-半乳糖苷酶活性诱导的EC50值分别为7.3×10-11mol·L-1和1.5×10-10mol·L-1,其中ER+GRIP1酵母细胞诱导产生的酶活性值明显高于ER+SRC1酵母细胞.4-OHT能够抑制E2诱导ER+GRIP1酵母细胞产生的酶活性,并存在显著的剂量-效应关系,IC50值为1.0×10-7mol·L-1.表明重组人雌激素受体基因酵母可以用于检测化合物和环境样品的类/抗雌激素活性.  相似文献   

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