双酚A对哺乳动物生殖系统影响的研究进展

现代工业中,双酚A(BPA)被广泛应用于聚碳酸酯塑料和环氧树脂的制造,同时其也是一种具有雌激素样作用的化合物.因其被大量使用,已造成人等哺乳动物广泛暴露其中.动物实验结果表明:雌性妊娠期或动物新生期暴露于BPA可诱发后代或动物幼年的性早熟、乳腺组织发育异常、前列腺组织增生及雄性精子生成下降等,最终会导致乳腺组织的癌前病变及生殖道的严重损害.另外,对暴露BPA的人群调查也发现,BPA对生殖系统有明显的毒性作用,其中包括可导致男性性功能障碍等.     

糖尿病对生殖系统的影响

近年来,糖尿病的发病率在全球范围内不断上升,其并发症严重影响着患者的身心健康。糖尿病对患者生殖系统的损伤备受关注,包括：生殖器官结构、生殖激素合成和分泌、生殖细胞发生和功能、性功能及子代健康等,尤其是其损伤的病理机制,其中涉及激素水平、细胞和分子水平的调节障碍。因此,研究糖尿病对生殖系统的影响及其病理机制对糖尿病患者生殖系统疾病的预防、诊断和治疗都有重要的临床意义。     

睡眠障碍对生殖系统影响的研究进展

随着学习、工作压力的增加、生活节奏的加快,睡眠障碍在青少年及中年人群中越发突出,具有很高的发病率,且已严重危害该人群的身心健康。近年来,睡眠障碍对生殖系统的损伤逐渐受到关注,其中包括:性行为、性激素代谢、生殖细胞发生与成熟、妊娠、胚胎发育及子代健康等发生异常,其病理机制可涉及机体的神经内分泌系统、免疫系统及氧化应激反应等。因此,研究睡眠障碍对生殖系统的影响并阐明其病理机制对于该病的预防及临床治疗,尤其是警示人们生活方式的改变均有重要的理论和社会意义。     

妇科门诊患者生殖系统病原体感染情况分析

目的 分析妇科门诊患者生殖系统病原体感染情况,为临床上能正确诊断和治疗提供科学依据.方法 选取妇科门诊治疗的436例生殖系统感染患者,根据临床症状和相关病史分为炎性反应组(317例)和非炎性反应组(119例),采用不同的方法对各种病原体进行培养,在超高显微镜下进行观察,分析各种病原体的阳性率.结果 炎性反应组支原体、衣原体、念珠菌、滴虫、线索细胞感染率分别为43.53％(138/317)、48.26％(153/317)、13.56％(43/317)、64.98％( 206/317)、23.97％(76/317),均显著高于非炎性反应组的21.01％(25/119)、26.05％ (31/119)、7.56％(9/119)、10.08％(12/119)、14.29％(17/119),差异有统计学意义(P＜0.01或＜0.05).炎性反应组病原体混合感染者共160例,发生率为50.47％(160/317).结论 妇科生殖系统感染的主要病原体有支原体、衣原体、念珠菌、滴虫和线索细胞,混合感染在生殖系统感染中占主要地位,临床对妇科炎性反应标本进行病原体检查要全面准确.     

空气污染物对哺乳动物生殖和胚胎发育的影响

日益严重的空气污染已对人们的生命健康构成巨大的危害。大量的流行病学研究表明,严重的空气污染对生殖系统有着多重负面影响。对男性而言,可导致睾丸体积减小和质量减轻,精子数量、浓度降低,运动力与形态学改变,并可引起精子染色体畸变、DNA断裂,最终表现为男性生殖功能的下降,导致不育。而对女性,空气污染与卵巢结构与功能受损、生殖细胞发育异常、排卵率下降以及雌激素分泌异常等显著相关。另外,长期暴露于空气污染的环境中,孕妇的流产率明显增高,且更易造成胎儿畸形的发生。综述多种主要空气污染物对男、女生殖器官(系统)、生殖细胞、生殖功能及胚胎发育影响的最新研究进展。     

Krüppel样因子家族在女性生殖系统疾病中的研究进展

女性生殖系统疾病很大程度上与雌、孕激素及其受体介导信号通路失调所致细胞增殖、凋亡和分化异常有关。这些核受体的精细调控是复杂的,许多核因子参与其中。Krüppel样因子(Krüppel-like factors,KLFs)是一组与真核细胞转录调控密切相关的锌指蛋白,在女性生殖系统中普遍表达,作为类固醇激素反应的共同调控者和整合者。KLF4在子宫内膜异位症(EMs)患者的在位内膜和子宫内膜肿瘤中表达减少。围着床期,KLF5在子宫内膜容受性的形成中起重要作用,与胚胎成功植入有关。KLF6参与胎盘发育和妊娠的维持。KLF9对孕激素受体起正向调节作用,而对雌激素受体起到负向调节作用。KLF11是一种转录抑制因子,具有潜在地抑制子宫肌瘤、EMs异位病灶生长的功能。深入探讨KLFs的生物功能,对认识女性生殖系统疾病的发病机制有重要意义。     

沉默信息调节因子3及其在活性氧簇介导的生殖系统疾病中的作用

沉默信息调节因子3(sirt3)是定位于哺乳动物线粒体基质、依赖烟酰胺腺嘌呤二核苷酸(NAD+)的Ⅲ型组蛋白去乙酰化酶(HDACs)sirtuin家族成员之一,通过去乙酰化组蛋白发挥作用,并且完成线粒体中大部分蛋白质的去乙酰化。sirt3去乙酰化从转录因子到代谢酶类等底物[如缺氧诱导因子1(HIF-1)、p53、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)等因子,抗氧化酶过氧化氢酶(CAT)、谷氨酸脱氢酶(GDH)、过氧化氢酶和超氧化物歧化酶1(SOD1)等代谢酶类],影响活性氧簇(ROS)水平,导致胚胎发育潜能下降、卵巢功能衰退、卵巢肿瘤等生殖系统疾病的发生。总结sirt3的生物学特性、sirt3调控ROS水平的相关分子机制,进而为sirt3在ROS介导的生殖系统疾病的研究提供新思路。     

淫羊藿（苷）对男性生殖系统的作用和机制

淫羊藿是一种常用的中药材,淫羊藿苷是从淫羊藿中提取的一种黄酮类化合物,也是淫羊藿中最主要的活性物质。研究发现,淫羊藿苷具有促进成骨细胞的生成和活化、调节免疫、抗衰老和抗炎等多种功能。临床上淫羊藿（苷）用于治疗生殖系统、骨关节系统、呼吸系统、神经系统、心血管系统和免疫系统等多种疾病。淫羊藿（苷）对男性生殖系统的作用及机制主要包括具有雄性激素样作用,促进睾内睾酮的合成和分泌。淫羊藿（苷）通过改善精子发生的微环境、增强睾丸抗氧化作用促进精子生成,增加精子密度,改善精子活力,减缓生殖衰退。此外,淫羊藿（苷）可促进阴茎勃起,治疗勃起功能障碍及早泄。     

Krüppel样因子家族在女性生殖系统疾病中的研究进展

女性生殖系统疾病很大程度上与雌、孕激素及其受体介导信号通路失调所致细胞增殖、凋亡和分化异常有关。这些核受体的精细调控是复杂的,许多核因子参与其中。Krüppel样因子（Krüppel-like factors,KLFs）是一组与真核细胞转录调控密切相关的锌指蛋白,在女性生殖系统中普遍表达,作为类固醇激素反应的共同调控者和整合者。KLF4在子宫内膜异位症（EMs）患者的在位内膜和子宫内膜肿瘤中表达减少。围着床期,KLF5在子宫内膜容受性的形成中起重要作用,与胚胎成功植入有关。KLF6参与胎盘发育和妊娠的维持。KLF9对孕激素受体起正向调节作用,而对雌激素受体起到负向调节作用。KLF11是一种转录抑制因子,具有潜在地抑制子宫肌瘤、EMs异位病灶生长的功能。深入探讨KLFs的生物功能,对认识女性生殖系统疾病的发病机制有重要意义。     

塑料拆解地区水环境中DEHP检测

目的 监测某塑料拆解地区水环境中邻苯二甲酸二(2-乙基己基)酯(DEHP)的污染水平及探讨其可能的来源,为保护当地环境、促进居民健康提供基础数据。方法 用固相萃取和气相色谱联用技术检测河水、井水、塘水、无组织排放水和饮用水中DEHP水平。结果 各类水样中均检出DEHP,检出率为100%。河流污染断面DEHP平均浓度2.05μg/L,为清洁断面平均浓度(0.32μg/L)的6.4倍。暴露区井水(14.20μg/L)和塘水(135.68μg/L)DEHP的平均浓度分别为对照组井水(0.79μg/L)和塘水(0.37μg/L)的18和367倍。暴露区无组织排放水样中DE-HP的检出范围在0.36~161.86μg/L。结论 塑料拆解地区井水、塘水和无组织排放水样中均检出DEHP,且DEHP的平均浓度均超过中国《生活饮用水卫生标准》(GB5479-2006)和《地表水环境质量标准》(GB3838-2002)的要求,应引起重视。     

Di(2-ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and platelet donors

Each year thousands of healthy volunteers undergo apheresis procedures to donate blood components and safe lives. However, many disposables used in apheresis contain di(2-ethylhexyl)phthalate (DEHP). This way, donors are exposed to DEHP, which is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. We quantified the DEHP exposure of six plasma donors, six discontinuous-flow platelet donors and six continuous-flow platelet donors by determining three specific metabolites in urine (5OH-MEHP: mono(2-ethyl-5-hydroxyhexyl)phthalate; 5oxo-MEHP: mono(2-ethyl-5-oxo-hexyl)phthalate and MEHP: mono(2-ethylhexyl)phthalate). We found maximum concentrations in urine samples after the discontinuous-flow plateletpheresis procedure with 826 microg/l for 5OH-MEHP, 774 microg/l for 5oxo-MEHP and 266 microg/l for MEHP (mean of the six volunteers). Metabolite excretions were found to be significantly (p<0.0001) higher for both plateletpheresis techniques compared to plasmapheresis and controls. Continuous-flow plateletpheresis led to significantly higher (p<0.0001) excretions than discontinuous-flow plateletpheresis. Mean absolute DEHP exposures were 1.2 mg for discontinuous- and 2.1 mg for continuous-flow plateletpheresis. Exposure for plasmapheresis (0.37 mg) was in the range of the controls (0.41 mg). Mean DEHP doses for both plateletpheresis techniques (18.1 and 32.3 microg/kg/day) were close to or exceeded the reference dose (RfD) of the US EPA and tolerable daily intake (TDI) value of the EU on the day of the apheresis. Therefore, margins of safety might be insufficient to protect especially young men and women in their reproductive age from effects on reproductivity. At present, discontinuous-flow devices should be preferred to avert conceivable health risks from plateletpheresis donors. Strategies to avoid DEHP exposure of donors during apheresis need to be developed.     

不同烹调油样品中邻苯二甲酸二丁酯与邻苯二甲酸二（2-乙基己基）酯的分析

[目的]了解不同烹调油样品中邻苯二甲酸二丁酯（di-n—butyl phthalate,DBP）与邻苯二甲酸二（2-乙基己基）酯[di（2-ethylhexyl）phthalate,DEHP]的污染情况。[方法]采用气相色谱-质谱联用仪的选择离子检测（SIR）方式,测定取自居民家中未加热食用油、烹调剩油和厨房抽油烟机内油盒中的烹调油烟冷凝物,食堂中未加热食用油、烹调剩油和烹调油烟冷凝物;小摊贩所用的未加热食用油及其锅内剩油;快餐店未加热过的固体起酥油及烹调剩油等样品中DBP与DEHP的含量。[结果]9户居民家庭厨房和食堂不同烹调油样品中DBP和DEHP均为阳性,且烹调油烟冷凝物中的含量明显高于未加热食用油和烹调剩油中的含量;DBP和DEHP含量：前者分别为2．29～597．01μg／g和38．96～4774．72μg／g;后者分别为3．22～42．81μg／g和15．61～112．64μg／g。小摊贩和快餐店不同烹调油样品中,仅1例炸面食剩油检出DBP和DEHP。[结论]大部分烹调油样品被DBP、DEHP污染,且烹调油烟冷凝物中的含量大大增加。     

邻苯二甲酸二-(2-乙基己基)酯对小鼠胚胎发育毒性的体外实验研究

为探讨邻苯二甲酸 二 2 乙基己基酯 (Di 2 ethylhexylphthalate ,DEHP)对体外培养小鼠胚胎的发育毒性 ,采用植入后全胚胎培养模型 ,将 8.5天龄Balb c小鼠胚胎移入含DEHP即刻离心血清培养 48h ,DEHP终浓度为 0、12 .5、2 5、5 0、10 0和 2 0 0mg L ,观察DEHP对小鼠胚胎生长发育和组织器官形态分化的影响。结果显示DEHP对体外培养小鼠胚胎生长发育毒性的最大无作用剂量为 12 .5mg L ,≥ 2 5mg L的DEHP可诱发胚胎生长迟缓及组织器官形态分化异常 ,出现心脏、神经系统、腮弓发育异常及小肢芽、体位异常等畸形 ;10 0mg L的DEHP对体外培养胚胎偶尔呈致死效应 ;2 0 0mg L时各组织器官形态分化均出现了异常 ,但未发现死胎。上述改变具有明显的剂量 -效应及剂量 -反应关系。提示DEHP对体外培养的小鼠胚胎具有胚胎毒性 ,并以致畸效应为主     

The IARC Evaluation of Di(2-ethylhexyl)phthalate (DEHP): A Flawed Decision Based on an Untested Hypothesis

Abstract

The health impact of utilization of raw domestic sewage for vegetable cultivation in the suburbs of Asmara, Eritrea, was assessed. Results showed heavy contamination of vegetables by fecal coliforms and Giardia cysts as well as other pathogenic bacteria such as Shigella and Salmonella. Stool samples from 75 occupationally exposed farmers revealed that 45% of them were harboring Giardia cysts. Dietary intake of raw greens (lettuce, cabbage) grown on the raw sewage appears to cause giardiasis, amebiasis, and diarrhea in the farming community as well as in the surrounding area. Comparison of hospital data from the affected area with data from other areas of Eritrea indicated that agriculture use of untreated wastewater was the major cause of the increase in giardiasis and other gastrointestinal diseases.     

Internal exposure of nursery-school children and their parents and teachers to di(2-ethylhexyl)phthalate (DEHP)

Di(2-ethylhexyl)phthalate (DEHP) is the main plasticizer for polyvinyl chloride (PVC) products. It has become widely spread in our environment and among people. DEHP is suspected to be responsible for endocrine-disruptor-like effects in mankind. Children are probably most susceptible to these endocrine effects. In this study we determined the internal exposure of nursery school children (aged 2-6 years) to DEHP and compared it to their parents' and teachers' exposure. The DEHP-metabolites mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP) were determined in first morning urine. The sum of the three DEHP metabolites in children's and in adults' urine was 90.0 and 59.1 micrograms/l respectively (median values; p = 0.074). Concentrations of the secondary metabolites 5OH-MEHP (median: 49.6 vs. 32.1 micrograms/l; p = 0.038) and 5oxo-MEHP (median: 33.8 vs. 19.6 micrograms/l; p = 0.015) were significantly higher in children than in adults. MEHP concentrations were low both in adults and children (median: 6.6 micrograms/l vs. 9.0 micrograms/l). Creatinine adjusted values should more accurately reflect the dose taken up with respect to body weight when comparing children with adults. Total creatinine adjusted DEHP metabolites in urine were significantly higher in children than in adults (median values: 98.8 vs. 50.9 micrograms/g creatinine; p < 0.0001). This also applied to the concentrations of both secondary metabolites 5OH-MEHP (55.8 vs. 28.1 micrograms/g creatinine; p < 0.0001) and 5oxo-MEHP (38.3 vs. 17.2 micrograms/g creatinine; p < 0.0001). Creatinine corrected concentrations for the monoester MEHP in children and adults were very similar (8.7 vs. 8.6 micrograms/g creatinine; p = 0.908). Based on the sum of the three determined metabolites we estimated the DEHP dose (in microgram/kg body-weight) taken up by children to be about twice as high as the dose taken up by adults. Routes of the ubiquitous exposure to DEHP remain indistinct. In children's urine the mean relative ratios of MEHP to 5OH-MEHP to 5oxo-MEHP were 1 to 7.1 to 4.9, in adults they were 1 to 3.4 to 2.1. This might indicate an enhanced oxidative metabolism in children. To date no information on the biological activity and toxicity of oxidative metabolites of DEHP is available. Since these are the major metabolites of DEHP toxicological data on these metabolites is urgently needed.     

邻苯二甲酸二(2-乙基己基)酯对青春前期雄性大鼠的生殖毒性

目的探讨邻苯二甲酸二(2-乙基己)酯(di-2-ethylhexyl phthalate,DEHP)对青春前期雄性大鼠的生殖毒性。方法将32只健康21日龄清洁级雄性SD大鼠按体重随机分为4组,分别为溶剂对照(玉米油)组和250、500、1 000 mg/kg DEHP染毒组,每组8只。采用灌胃方式进行染毒,染毒容量为10 ml/kg,每天1次,连续染毒4周。采用CASA精子分析系统分析精子活力相关指标。结果与对照组比较,1 000 mg/kg DEHP染毒组大鼠的精子密度、精子活动率、活动精子密度、最大侧摆幅度、直线运动的精子密度及A级精子百分率均较低,而D级精子百分率较高;250 mg/kg DEHP染毒组平均直线运动速度、精子运动的向前性均较低;500、1 000 mg/kg DEHP染毒组直线运动的精子个数均较低,差异均有统计学意义(P0.05);而各剂量DEHP染毒组B、C级精子比例和平均曲线运动速度、平均路径速度、平均侧摆幅度、平均鞭打频率、运动的直线性、运动的摆动性、平均移动角度、直线运动精子活率均无明显改变。结论 DEHP对青春前期雄性大鼠精子活力产生明显的毒性作用,从而影响雄性的生殖功能。