典型杀虫剂类内分泌干扰物对水生溞类的毒性效应研究进展

内分泌干扰物(endocrine disrupting chemicals, EDCs),尤其是具有内分泌干扰效应的杀虫剂,因能显著影响水生生物的生长发育和生殖系统,其潜在生态毒性效应引起了人们的广泛关注。溞类在水生生态系统食物链中起着重要的连接作用,更易受到水体中残留的杀虫剂类EDCs的影响,其毒性效应在水生生态系统毒理学研究中有着重要的意义。本文重点综述了杀虫剂类EDCs对溞类产生的生长发育毒性和生殖毒性,从酶活性变化角度分析由此产生的氧化应激和神经毒性,并在基因表达水平上揭示其毒性作用机制,发现杀虫剂类EDCs通过扰乱神经系统和内分泌系统发挥作用,并展望了杀虫剂EDCs在联合毒性、多代效应的研究前景,旨在为研究杀虫剂类EDCs对大型溞的毒性作用和生态环境风险评估提供依据。     

多溴二苯醚及其代谢物的内分泌干扰活性和构效关系研究进展

多溴二苯醚(Polybrominated diphenyl ethers,PBDEs)作为一种良好的防火溴系阻燃剂(Brominated flame retardants,BFRs)广泛应用于各种家用和工业产品.研究表明,PBDEs容易从产品中溢出而进入环境.近年来,PBDEs及其代谢物已在各种环境介质和生物体中被广泛检出.毒理学研究发现,PBDEs及其代谢物具有生殖毒性、免疫毒性、神经毒性和内分泌干扰作用.在总结国内外相关研究基础上,论文综述了PBDEs及其代谢物的内分泌干扰活性,重点集中在对甲状腺激素活性、雌激素活性、雄激素活性及影响性激素转化和代谢的芳香化酶、CYP17酶、雌二醇磺基转移酶(E2SULT)活性的影响;分析了具有不同测试终点内分泌干扰活性的化合物的结构特征.研究发现,在内分泌干扰活性方面,PBDEs母体化合物的影响较小,主要是PBDEs代谢物产生的影响,特别是羟基化代谢物引起了较严重的内分泌干扰作用,即PBDEs化合物是一类通过代谢而被活化的内分泌干扰前趋物.为评价PBDEs及其代谢物对人和其他生物的健康危害,应加强其内分泌干扰活性机制的研究,以及具有同类型作用模式的PBDEs及其代谢物定量结构-活性关系的研究.     

邻苯二甲酸酯类增塑剂的体外细胞毒性评价

邻苯二甲酸酯(Phthalate esters, PAEs)是环境介质中的一类典型的有机污染物。已有研究表明,PAEs具有明显的内分泌干扰毒性,并会对动物和人体的生殖发育与神经系统造成损伤。体外细胞评价模型因具有高通量、测试周期短、成本低和毒性效应易于探明等技术优点,被广泛应用到PAEs毒理学效应的研究中。本文从内分泌干扰毒性、胚胎发育毒性、神经毒性、免疫毒性、遗传毒性以及致癌作用等方面,对PAEs的一些体外细胞毒性评价模型进行了分类和总结,并对其相应的研究进展进行了综述。本文旨在为体外细胞毒性评价模型的有效利用提供借鉴,并对PAEs毒性作用机制的深入研究提供思路和依据。     

多氯联苯羟基化代谢物及其雌激素效应研究进展

多氯联苯作为一种环境内分泌干扰物,具有一定的雌激素干扰效应,导致动物雌激素水平紊乱或功能异常,从而影响生殖、发育或行为。羟基多氯联苯是多氯联苯最主要的活性代谢产物,已经在动物和人体组织中被检出。羟基多氯联苯的化学性质和分子空间构象使其雌激素干扰效应可能较母体化合物更强。因此,它们对人类和动物机体的潜在影响以及由此带来的新的毒理学问题成为内分泌干扰研究领域的热点之一,相关的毒性作用机制需要进一步探索。本文对多氯联苯的代谢途径、羟基多氯联苯在生物体内的暴露水平、雌激素干扰效应及作用机制进行综述。     

雌激素受体作为壬基酚的主要作用靶点导致机体免疫毒性

雌激素作为一类重要的性腺类固醇化学信使,已经被证实能够直接调节机体免疫反应,因此,一些具有拟雌激素特性的环境内分泌干扰物(endocrine disruptors,EDs),会通过影响雌激素相关信号通路对免疫系统产生干扰作用。壬基酚(nonylphenol,NP)作为典型的环境内分泌干扰物,已有大量的文献报道其通过拟雌激素特性或干扰雌激素的合成、分泌、转运以及与靶点的结合,破坏机体生殖功能以及神经-免疫-内分泌系统,影响整体生理平衡与稳定。近年来,NP对免疫系统的干扰作用逐渐引起重视,研究发现,NP暴露会引起小鼠免疫器官及免疫细胞的发育异常,并且会导致新生小鼠肝毒性,肝脏细胞内炎性因子TNF-α、IL-1β分泌增加。除NP作为配体干扰雌激素信号通路外,尚未发现其他明确的分子机制解释NP造成的免疫毒性。本综述主要结合近年来相关的实验结果,总结了NP对免疫系统的潜在影响及其可能的分子机制。     

基于模式生物秀丽隐杆线虫的环境污染物生殖毒性研究进展

由于人类社会的发展,环境污染也越来越严重,研究环境污染物对生态及人类健康的影响极为重要。生殖系统是人和动物繁衍后代的重要系统,常见环境污染物对生殖系统的影响正引起研究人员的广泛关注。秀丽隐杆线虫具有身体透明、品系丰富和遗传背景清楚等优点,为生殖毒理学研究提供了一个便利的平台。以秀丽隐杆线虫为模型已对多种环境污染物的生殖毒性进行了评价。本文重点叙述了重金属、纳米材料、有机物等化学污染,辐射、磁场等物理污染,以及病毒等生物污染对秀丽线虫生殖系统的影响,并归纳讨论了环境污染物造成生殖功能障碍的几种主要机制,如氧化应激、DNA损伤、内质网应激以及神经损伤等,但不同类型污染物的毒性效应与其自身的物化性质紧密相关。环境污染物诱导的生殖毒性中不同响应机制之间的关联性、不同发育阶段的敏感性差异、污染物的传代效应以及有效的缓解方式的筛选等都有待进一步的开展。     

粮食真菌毒素的生殖、发育与遗传毒性:现状与展望

粮食及其制品会受到多种真菌毒素的污染。粮食真菌毒素现已被证实具有多种毒性作用,如细胞毒性、发育毒性、生殖毒性、免疫毒性和遗传毒性等,严重危害人和动物健康,甚至还会对间接或未接触毒素的子代产生不良影响,但目前有关继代毒理学数据极为缺乏。本文主要阐述了粮食中常见真菌毒素对亲本世代及其子代生殖系统/能力和生长发育的影响,简述了不同毒素诱导生殖发育毒性的作用机理并提出展望,旨在全面了解粮食真菌毒素的生殖发育及遗传毒性作用,为进一步开展粮食真菌毒素的健康风险评估,合理制定相关限量标准与法规,指导公共卫生健康并开展主动防治与干预提供重要理论依据。     

内分泌干扰物壬基酚在环境中迁移转化的研究进展

作为一种内分泌干扰物,壬基酚(Nonylphenol,NP)是壬基酚聚氧乙烯醚(NPnEO)的主要降解产物,具有高亲脂性、难降解性、生物累积性和高毒性.全面了解NP在环境中的迁移转化规律是对其进行科学的风险评价的基础.本文归纳和分析了近几年国内外学者有关NP在环境中的分布情况及其迁移转化的研究动态,从来源、分布及其在环境中主要的迁移转化过程和机理等方面分别论述了内分泌干扰物壬基酚在环境中的行为,重点讨论了NP在沉积物和土壤中的吸附-解吸和生物降解的机理及影响因素,最后指出了今后的主要研究方向.     

EEDs对鱼类性激素合成途径干扰作用研究进展

环境内分泌干扰物(environmental endocrine disruptors,EEDs)是一类可以改变生物体内激素的合成、释放、运输、代谢、结合、作用或清除等一系列生物过程的外源物质。性激素的生物合成需要一系列酶的参与,体内和体外研究表明,性激素合成途径中的类固醇生成酶是EEDs通过非性激素受体介导途径发挥内分泌扰乱作用的重要靶点,性激素合成途径的扰乱可能导致生物体生殖系统受损。本文综述了EEDs对鱼类性激素合成底物和类固醇生成酶的影响、信号转导机制及其生殖危害;并对性激素合成途径中促性腺激素调控机理、多种转录因子间的相互作用、不同物种间类固醇生成酶的差异以及各内分泌轴线的相互作用研究进行了展望,以期为EEDs通过非性激素受体介导途径发挥内分泌干扰效应的机制研究提供思路。     

室内环境中持久性卤代有机污染物的人体暴露及潜在生殖健康影响

卤代持久性有机污染物(Hal-POPs),如多溴联苯醚(PBDEs)、多氯联苯(PCBs)、滴滴涕(DDT)等是环境中广泛存在的全球性有机污染物,同时它们又是内分泌干扰物,是威胁人类生殖健康的重要因素之一。由于人们每天约有80%以上的时间在室内度过,且室内环境是Hal-POPs人体暴露的主要来源之一,因此室内环境中Hal-POPs对人体内分泌系统的干扰作用及其机理等问题亟待研究,但目前这方面的研究很有限。本文通过综述Hal-POPs在室内环境中的赋存水平和在人体体内的负荷水平及其半衰期,探讨了其对人体内分泌系统尤其是男性生殖健康的影响情况及其可能的机理,并分析了目前研究的不足之处及研究前景,为进一步开展这方面的研究提供借鉴。     

近海沉积物DlPCBs对斑马鱼胚胎EROD和cyp1a mRNA的影响

为探究湛江近海域海洋沉积物中类二噁英多氯联苯(dioxin-like polychlorinated biphenyls,Dl PCBs)的生物学毒性效应,选取湛江近海域2个地点(近工业区TS和近生活区JSW)采集沉积物样品,制备近海域沉积物Dl PCBs提取物,将斑马鱼胚胎暴露于不同浓度的Dl PCBs提取物,测定斑马鱼胚胎7-乙氧基异吩恶唑脱乙基酶(ethoxyresorufin-O-deethylase,EROD)活性和cyp1a m RNA相对表达量。结果发现,JSW采样点Dl PCBs提取物染毒组EROD酶活性变化与TS采样点Dl PCBs提取物一致,在各染毒浓度下,斑马鱼仔鱼EROD酶活性为对照组的1.1~1.8倍。TS和JSW采样点不同浓度Dl PCBs提取物暴露斑马鱼胚胎96 h后,使斑马鱼仔鱼cyp1a m RNA相对表达量是对照组的3.36~19.45倍。说明一定浓度的近海沉积物Dl PCBs能诱导斑马鱼仔鱼EROD酶活性和cyp1a m RNA表达量升高,且呈现浓度-效应关系。     

非洲爪蟾在生态毒理学研究中的应用（Ⅲ）——生殖内分泌干扰作用的评价

两栖动物生殖内分泌系统(如性别分化、性腺发育、第二性特征)对性激素的敏感性,使得该类动物可用于研究内分泌干扰物(Endocrine Disrupting Chemicals,EDCs)对生殖内分泌系统的干扰作用.两栖动物非洲爪蟾是发育生物学研究的经典模型动物,多年来积累的有关其生殖内分泌的资料可以为生殖内分泌干扰的研究提供参考.论文分析了非洲爪蟾作为评价生殖内分泌干扰作用模型动物的理论基础,总结了评价生殖内分泌干扰作用目前使用的几个指标(性别分化、性腺形态、性腺组织学结构、性激素水平、卵黄蛋白原表达等生物标记),综述了非洲爪蟾在评价酚类化合物、阿特拉津、多氯联苯等几种EDCs的生殖内分泌干扰作用中的应用,最后讨论了非洲爪蟾作为一种评价EDCs生殖内分泌干扰作用的模型动物目前存在的问题.毫无疑问,非洲爪蟾是生殖内分泌干扰研究的良好模型动物,为促进该模型动物更好的应用,需要加强非洲爪蟾生殖生物学和内分泌学的研究.     

邻苯二甲酸二(异)丁酯及其替代品的内分泌干扰效应研究进展

邻苯二甲酸二丁酯(di-n-butyl phthalate, DnBP)和邻苯二甲酸二异丁酯(diisobutyl phthalate, DiBP)是广泛用于塑料、树脂和橡胶制品中的邻苯二甲酸酯类增塑剂,曾在各种环境介质中频繁检出.现有研究表明,DnBP和DiBP对人类和其他动物具有显著的内分泌干扰效应以及生殖发育毒性等不良影响,因而在许多国家和地区被限制使用,由此市面上涌现出了一些替代品增塑剂.本文结合国内外关于DnBP和DiBP及其替代品的研究成果,综述了DnBP和DiBP在个体、细胞和分子水平上的内分泌干扰效应与机制以及在市场应用中的替代情况,并且选取了4种典型的替代品(邻苯二甲酸二异壬酯、环己烷-1,2-二羧酸二异壬酯、二苯甲酸二聚丙二醇酯、三乙酸甘油酯)对其内分泌干扰效应进行对比分析.研究结果表明,DnBP和DiBP在环境低浓度下能够影响类固醇激素合成通路中关键基因的表达,进而改变生物体内类固醇激素的水平,高浓度暴露时则会对生殖器官造成损伤并最终降低生殖能力,妊娠期暴露还会对后代产生相同的影响.DnBP和DiBP的4种替代品在急性毒性、持久性和生物可累积性方面均有所降低,内分泌干扰效应也显著降低,但缺乏系统的研究以全面评估其可替代性.提出今后替代品的安全性评估应纳入更多的毒性终点并深入研究相关的毒性效应机制,以保证替代化学品的安全性.     

Male–female socio-spatial relationships and reproduction in wild chimpanzees

Recent research on primates and other taxa has shown that the relationships individuals form with members of the same sex affect their reproductive success. Evidence showing that intersexual relationships also influence reproduction, however, is more equivocal. Here, we show that male chimpanzees living in an exceptionally large community display long-term tendencies to associate with particular females. These association patterns are likely to arise because individuals of both sexes selectively range in specific areas of the communal territory, with males inheriting the ranging patterns of their mothers. These differentiated male–female socio-spatial relationships involved males of widely varying ranks, and their effect on reproduction is as strong as that of male dominance rank, which in turn is as strong a predictor of reproductive success at Ngogo as in other smaller chimpanzee communities. These results show that male–female socio-spatial relationships can play a large role in chimpanzee male reproductive strategies, although they probably neither weaken nor strengthen the relationship between male dominance rank and reproductive success. Our results linking male–female socio-spatial relationships to reproduction in chimpanzees suggest that the gap between the social and mating systems of humans and their closest living relatives may not be as large as previously thought.     

Hormonaktive Xenobiotika

Developmental and reproductive processes are most sensitive to the toxic effects of environmental chemicals. Especially alarming is the fact that many groups of industrial chemicals and pesticides are capable of disrupting the endocrine system in man and animals. Of great concern is the reduction in the sperm count in Europe, but also the worldwide increase in a great number of reproductive and developmental disturbances observed in both man and wildlife. A correlation to a high chemical burden has been demonstrated for many different animal species as well as for women. An important consideration in assessing the potential effects of environmental chemicals on the endocrine system is the time at which such an exposure occurs. In the adult organism, hormones initiate functional processes; these effects are usually transient. In early life, hormones control developmental processes and are capable of producing permanent changes in organ structure and function (organizational effects). Therefore, chemical disruption of hormonal functions during development can result in permanent functional changes of the afflicted organ.     

Social rank, fecundity and lifetime reproductive success in wild European rabbits (Oryctolagus cuniculus)

Wild European rabbits of both sexes have separate linear rank orders, which are established and maintained by intensive fights. This paper presents data from a 14-year study (1987-2000) on the population physiology and behavioural ecology of wild rabbits living in a 22,000 m² enclosure and focuses on the relationship between social rank and reproduction in females. Group composition, social ranks, fecundity and reproductive success were known for all females (n=197) from the outset of their first reproductive season at an age of about 300 days until their death. The annual reproductive success of females was influenced to a large extent by their social rank. This depended on two effects of about equal strength: a higher fecundity of high-ranking females and a lower mortality of their offspring between birth and adulthood. The lifetime reproductive success of the females varied greatly. Only about 50% of all females had any reproductive success (range: on to nine adult offspring). The social rank achieved by the females during their first reproductive season substantially influenced their lifetime reproductive success: The mean reproductive lifespan and lifetime fitness of high-ranking females (ranks 1 and 2) was about 60% greater than that of lower-ranking females, although many of the latter also gained dominant positions in subsequent years.     

The roach (Rutilus rutilus) as a sentinel for assessing endocrine disruption.

Alterations in development and reproduction as a consequence of exposure to endocrine-disrupting chemicals (EDCs) have been demonstrated in many wildlife species. Animals living in, or closely associated with, the aquatic environment are particularly vulnerable to endocrine disruption because thousands of chemicals are actively disposed into rivers, estuaries and seas. Fish have thus been a focus in endocrine disruption studies, and some of the most comprehensive studies on the disruption of sexual development and function are on the roach (Rutilus rutilus). This paper provides a critical analysis of the roach as a sentinel for studies into endocrine disruption. The paper starts by describing what is known on the basic reproductive biology of the roach, information essential for interpreting chemical effect measures on sexual development and function. We then analyze where and how the roach has been applied to improve our understanding of the estrogenic nature of discharges from wastewater treatment works (WWTWs) and describe the phenomenon of feminized male roach in UK rivers. In this paper, the causation of these effects and issues of relative susceptibility and sensitivity of the roach to the effects of estrogenic EDCs are addressed. The paper then describes the ongoing work on the development of genetic and genomic resources for roach and analyses how these are being applied in studies to understand the mechanisms of disruption of sexual development. Finally, the paper addresses the biological significance of sexual disruption and intersex for the individual and discusses the possible implications for wild populations.     

计算毒理学在内分泌干扰物筛选上的应用和展望

内分泌干扰物通过干扰内分泌系统导致多种疾病,如生殖疾病、肥胖症甚至癌症。然而,面对环境中大量潜在的内分泌干扰物,传统的体外、体内评估方法由于成本高、耗时长等问题,难以实现内分泌干扰物的高通量筛查。计算毒理学逐渐发展成为被美国环保局(Environmental Protection Agency,EPA)、经济合作与发展组织(Organization for Economic Co-operation and Development,OECD)等机构所推荐的内分泌干扰物筛选与预测方法。本文综述了计算毒理学在内分泌干扰物筛选上的进展,主要包括分子对接和分子动力学模拟的应用,并对有害结局路径(adverse outcome pathway,AOP)的方法进行介绍和展望。