Origins and mechanisms leading to aneuploidy in human eggs

The gain or loss of a chromosome—or aneuploidy—acts as one of the major triggers for infertility and pregnancy loss in humans. These chromosomal abnormalities affect more than 40% of eggs in women at both ends of the age spectrum, that is, young girls as well as women of advancing maternal age. Recent studies in human oocytes and embryos using genomics, cytogenetics, and in silico modeling all provide new insight into the rates and potential genetic and cellular factors associated with aneuploidy at varying stages of development. Here, we review recent studies that are shedding light on potential molecular mechanisms of chromosome missegregation in oocytes and embryos across the entire female reproductive life span.     

Effects of environmental contaminants on fertility and reproductive health

Recent research indicates that the human infertility rate is increasing. Although various reasons have been hypothesized for the growing infertility rate, environmental contaminants are potentially important causal agents associated with this change. Chemical contaminants are widespread throughout our environment and human exposure is virtually unavoidable. The overall contribution of environmental exposure to infertility is unknown, but studies involving occupational exposure, together with results from animal experiments, suggest that environmental contaminants may adversely affect fertility. We reviewed the adverse effects of environmental exposure on fertility and related reproductive outcomes. Environmental contaminants covered in this review include heavy metals, organic solvents, pesticides and endocrine disrupting chemicals. It is hoped that this review will highlight the need for further research in this area.     

Chemicals,man and the environment

The interaction of chemicals with biological organisms is as old as life itself. Chemical pollution is usually considered to be human interference with natural chemical cycles and the release of man-made, unnatural compounds. The article traces five areas of chemical pollution and health hazards: air pollution, water pollution, occupational exposure, pollution from agricultural practices and contamination of food. It is suggested that historic perspective can aid in rational and prudent evaluation of present-day pollution problems.     

邻苯二甲酸酯类化合物生物降解动力学

用改进的鼓泡衰变实验装置,对五种邻苯二甲酸酯进行生物降解反应动力学研究。发现氮单胞菌属(Azomonas)是降解这类化合物的有效菌种,除邻苯二甲酸二辛酯外,其它四种在经过28天反应之后,降解率在98%以上。生物降解反应速率符合一级反应动力学方程。     

邻苯二甲酸酯暴露的大鼠尿液生物标志物研究

建立了检测尿液中邻苯二甲酸酯类化合物(PAEs)共同水解产物邻苯二甲酸(PA)的分析方法;通过雄性成年SD大鼠代谢试验,检测了邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二(2-乙基己基)酯(DEHP)单独暴露、以及联合暴露条件下大鼠尿液中PA总量,并分析了PA与暴露总量之间的关系.结果显示,随着暴露剂量的增大,尿液中排出的PA总量也不断增大;DBP单独暴露、DEHP单独暴露以及两者联合暴露时尿液PAEs代谢物平均排泄总量占摄入量的百分比分别为65.04%、55.00%和38.35%;大鼠尿液中PA的摩尔总量与DBP、DEHP、以及两者联合暴露的摩尔量之间的相关系数分别为0.92(P<0.01)、0.56(P<0.01)、0.93(P<0.01).尿液水解后的PA能够反映PAEs类物质的总暴露水平,将来可能作为一种潜在的暴露生物标志物用于人群的PAEs暴露监测.     

Cellular arsenic transport pathways in mammals

Natural contamination of drinking water with arsenic results in the exposure of millions of people world-wide to unacceptable levels of this metalloid. This is a serious global health problem because arsenic is a Group 1 (proven) human carcinogen and chronic exposure is known to cause skin, lung, and bladder tumors. Furthermore, arsenic exposure can result in a myriad of other adverse health effects including diseases of the cardiovascular, respiratory, neurological, reproductive, and endocrine systems. In addition to chronic environmental exposure to arsenic, arsenic trioxide is approved for the clinical treatment of acute promyelocytic leukemia, and is in clinical trials for other hematological malignancies as well as solid tumors. Considerable inter-individual variability in susceptibility to arsenic-induced disease and toxicity exists, and the reasons for such differences are incompletely understood. Transport pathways that influence the cellular uptake and export of arsenic contribute to regulating its cellular, tissue, and ultimately body levels. In the current review, membrane proteins (including phosphate transporters, aquaglyceroporin channels, solute carrier proteins, and ATP-binding cassette transporters) shown experimentally to contribute to the passage of inorganic, methylated, and/or glutathionylated arsenic species across cellular membranes are discussed. Furthermore, what is known about arsenic transporters in organs involved in absorption, istribution, and metabolism and how transport pathways contribute to arsenic elimination are described.     

Exposure to polycyclic aromatic hydrocarbons and risk for premature ovarian failure and reproductive hormones imbalance

Polycyclic aromatic hydrocarbons (PAHs) are a typical class of persistent organic pollutants that is ubiquitous worldwide. Previous animal studies suggested that PAHs had adverse effects on female reproduction. However, the human data regarding relationship of PAHs exposure with women reproductive health, such as ovarian dysfunction, are scarce. In this case-control study, the associations of serum levels of PAHs with the risk of premature ovarian failure (POF) and reproductive hormones in Chinese women were investigated, with recruiting 157 POF patients and 217 healthy women. The serum levels of 12 types of PAHs, as well as reproductive hormones, including follicle-stimulating hormone, luteinizing hormone and anti-mullerian hormone, were determined. In the logistic regression models, most individual PAH congeners showed significantly positive correlations with the risk of POF (p < 0.05), except for fluorine and pyrene. Benzo(a)pyrene (BaP), as the most carcinogenic PAH congener, was observed to be significantly positively associated with the risk of POF. After adjustment for age, body mass index, educational levels and household income, per one-unit increase in the log-transformed BaP concentration was significantly correlated with 2.191-fold increased risk of POF (OR = 2.191, 95%CI: 1.634–2.938, p < 0.05). To the best of our knowledge, this is the first study to report an association between internal exposure levels of PAHs and the increased risk of POF in women.     

Low concentrations of atrazine, glyphosate, 2,4-dichlorophenoxyacetic acid, and triadimefon exposures have diverse effects on Xenopus laevis organ morphogenesis

Many chemicals are released into the environment, and chemical contamination has been suggested as a contributing factor to amphibian declines. To add to a growing body of knowledge about the impact of individual chemicals on non-target organisms, we examined the specificity of deformities induced by exposure to four pesticides (atrazine, 2,4-dichloropheoxyacetic acid (2,4-D), triadimefon, and glyphosate) in the model amphibian species, Xenopus laevis. We focused on the period of organ morphogenesis, as it is frequently found to be particularly sensitive to chemical exposure yet also commonly overlooked.We found similar levels of intestine malformations and edemas, as well as disruption of skeletal muscle, in atrazine and triadimefon exposed tadpoles. The e ects of 2,4-D were only apparent at the highest concentrations we examined; glyphosate did not induce dramatic malformations at the concentrations tested. While researchers have shown that it is important to understand how chemical mixtures a ect non-target organisms, our results suggest that it is first crucial to determine how these chemicals act independently in order to be able to identify consequences of individual pesticide exposure.     

Safer alternatives assessment: the Massachusetts process as a model for state governments

In 2006 the Massachusetts Toxics Use Reduction Institute conducted a study to determine if states could identify safer alternatives to five chemicals of concern. The chemicals investigated included di (2-ethylhexyl) phthalate (DEHP), formaldehyde, hexavalent chromium, lead and perchloroethylene. First, the Institute developed a methodology for assessing alternatives to these five chemicals that allowed it to quickly determine priority uses and alternatives to assess and to research the pertinent decision criteria, which included performance, technical, financial environmental and human health parameters. The methodology included important feedback from stakeholders in the state, which helped to focus and enhance the value of the work. Second, the Institute implemented the methodology over a ten month period. Based on the activities conducted by the Institute, safer alternatives were identified for each of the priority uses associated with the five chemicals studied. This report summarizes the methodology employed and provides examples of the results for one of the five chemicals, namely DEHP. The experience of the Institute and the information contained in this report indicates that alternatives assessment was a useful approach to organizing and evaluating information about chemicals and alternatives.     

Tetrabromobisphenol A (TBBPA): A controversial environmental pollutant

Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame retardants and is extensively used in electronic equipment, furniture, plastics, and textiles. It is frequently detected in water, soil, air, and organisms, including humans, and has raised concerns in the scientific community regarding its potential adverse health effects. Human exposure to TBBPA is mainly via diet, respiration, and skin contact. Various in vivo and in vitro studies based on animal and cell models have demonstrated that TBBPA can induce multifaceted effects in cells and animals, and potentially exert hepatic, renal, neural, cardiac, and reproductive toxicities. Nevertheless, other reports have claimed that TBBPA might be a safe chemical. In this review, we re-evaluated most of the published TBBPA toxicological assessments with the goal of reaching a conclusion about its potential toxicity. We concluded that, although low TBBPA exposure levels and rapid metabolism in humans may signify that TBBPA is a safe chemical for the general population, particular attention should be paid to the potential effects of TBBPA on early developmental stages.     

我国童装中邻苯二甲酸酯赋存特征及健康风险

为了解我国市售童装中邻苯二甲酸酯污染特征,选择了21种常见品牌的童装,采用Agilent 7890A/5975C气相色谱质谱联用仪,对其中16种PAEs(phthalate esters,邻苯二甲酸酯)进行测定,并应用美国国家环境保护局推荐的方法评估了其健康风险.结果表明,我国市售童装中w(∑₁₆PAEs) (16种PAEs的总含量)为2.97~40.0 mg/kg,平均值为11.0 mg/kg.其中,w(DEHP)〔DEHP为邻苯二甲酸(2-乙基已基)酯〕、w(DBP)(DBP为邻苯二甲酸二正丁酯)和w(BBP)(BBP为邻苯二甲酸丁基苄酯)三者之和为1.73~26.7 mg/kg,未超出GB 31701—2015《婴幼儿及儿童纺织产品安全技术规范》规定的限值;DIBP(邻苯二甲酸二异丁酯)、DBP、DEHP和DNOP(邻苯二甲酸二正辛酯)是含量较高的四种单体,四者之和占w(∑₁₆PAEs)的53.9%~96.8%(平均值为82.5%),可能与童装加工过程的人为添加有关.童装中DMP(邻苯二甲酸二甲酯)、DEP(邻苯二甲酸二乙酯)、DIBP、DBP、BBP、DEHP、DNOP和∑₇PAEs的非致癌风险值均远小于1.0,对儿童无明显非致癌风险, 但DEHP的致癌风险值接近10-6,应引起重视.      

典型设施农业土壤酞酸酯污染特征及其健康风险

采用超声提取、气相色谱-质谱技术和CalTOX模型,分析了南京城郊典型设施菜地土壤中6种酞酸酯的污染特征、污染负荷及其健康风险.结果表明,所有的土壤样品中均检测出酞酸酯,6种酞酸酯的总量为0.15~9.68mg/kg,其平均含量为2.21mg/kg;邻苯二甲酸二丁酯(DnBP)、邻苯二甲酸(2-乙基己基)酯(DEHP)和邻苯二甲酸二辛酯(DnOP)为该地区设施农业土壤的主要酞酸酯种类,其检出率分别为88.2%、100%和79.8%,含量范围分别在n.d.~1.83、0.02~9.03、n.d.~1.74mg/kg之间;土壤pH值和有机碳含量与土壤酞酸酯含量之间无显著相关性,研究区域土壤酞酸酯总体污染负荷为4.31kg/hm2;健康风险评价结果表明DnBP和DEHP的潜在健康风险较高,设施农业从业者的主要暴露途径通过皮肤接触;设施菜地土壤酞酸酯含量、污染负荷以及健康风险均显著高于周边地区露天菜地土壤.     

Pollution level and human health risk assessment of some pesticides and polychlorinated biphenyls in Nantong of Southeast China

Food consumption is one of the key exposure routes of humans to contaminants. This article evaluated the residue levels of 51 pesticides and 16 polychlorinated biphenyls (PCBs) in selected fish and food items which were commonly consumed in the Nantong area of Jiangsu Province, Southeast China. The 51 pesticides and 16 PCBs were analyzed by highly sensitive gas chromatography-tandem mass spectrometry (GC-MS/MS). The results showed that organochlorine pesticides such as dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB) and mirex and other pesticides including chlorpyrifos, pyrethroid pesticides, metolachlor, pyridaben and trifluralin were frequently detected in the samples, which was consistent with the accumulation level and characteristics of these toxic chemicals in human adipose tissue of people living in Nantong. Meanwhile, correlation of the residue level of toxic chemicals with their physical chemical properties and historic use pattern in Nantong area was observed. Combined with dietary survey results at the same sampling locations, human health risk assessment of ingestion through the dietary route was performed. The results suggested that the non-cancer risks of the chemicals investigated can be considered negligible in the Nantong area, however, the cancer risks from lifetime dietary exposure to DDTs and HCB have exceeded the acceptable levels.     

海洋藻类毒素的生态毒理学研究

从生态毒理学角度介绍了麻痹性贝毒(PSP)、腹泻性贝毒(NSP)、神经性贝毒(NSP)、记忆缺失性贝毒(ASP)和西加鱼毒素等几种主要海洋藻类毒素的一些研究进展,包括毒素对人类及海洋生物的毒性、毒素在食物链中的积累和转移、毒素的致毒途径、海洋生物对毒素的回避和选择性取食等。这些毒素可通过食物链在贝类或其他海洋动物体内积累并浓缩放大,从而危及人类健康,有的毒素还能直接对海洋生物产生毒害作用,破坏海洋生态环境。文中同时也介绍了该领域研究工作在我国开展情况及今后的研究方向。     

Interfacial effects of suspended particles on biodegradation of N (2,4 dimethyl phenyl) N'' methylformamidine hydrochloride and dibutyl phthalate in waters

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环境浓度下邻苯二甲酸二乙酯对秀丽隐杆线虫的生态毒理效应

DEP (diethyl phthalate,邻苯二甲酸二乙酯)是一种在环境中普遍存在的具有潜在神经和生殖毒性的增塑剂,其会干扰环境生物的发育水平、运动行为及生化水平.以秀丽隐杆线虫的体长、体宽、头部摆动频率及生化指标作为测试终点,评估环境中DEP对秀丽隐杆线虫的生态毒理效应.在不同环境浓度(0、0.000 2、0.002、0.02、0.2、2 mg/L)的DEP溶液中,对秀丽隐杆线虫进行不同时间(24 h、72 h和10 d)的暴露试验.结果表明:①在不同浓度DEP溶液中暴露24 h后,秀丽隐杆线虫的发育水平均未受到显著影响(P>0.05).②在不同浓度DEP溶液中暴露72 h后,秀丽隐杆线虫的发育水平受到干扰.与对照组相比,在DEP浓度最高(2 mg/L)时,秀丽隐杆线虫体长下降了3.21%(P < 0.05);在DEP浓度为0.000 2 mg/L时,秀丽隐杆线虫的体宽呈上升趋势,且头部摆动频率明显加快了5.52%(P < 0.01),秀丽隐杆线虫的发育水平受到显著抑制.③在不同浓度DEP溶液中暴露10 d后,与对照组相比,秀丽隐杆线虫的体长、体宽和头摆频率均出现下降;在DEP浓度为2 mg/L时,秀丽隐杆线虫体内活性氧自由基、脂褐素和细胞凋亡水平累积均增长显著,出现氧化应激损伤.研究显示,不同环境浓度的DEP溶液会对秀丽隐杆线虫产生一定的毒性影响,且不同暴露时间和暴露浓度产生的毒性影响也存在一定差异.      

邻苯二甲酸二(2-乙基己基)酯对罗非鱼肝脏转录组影响研究

邻苯二甲酸二（2-乙基己基）酯（DEHP）作为生产量和使用量最多的一种邻苯二甲酸酯类化合物,其对水生生物具有多种毒性.本研究选用中国南方地区最重要的经济鱼类尼罗罗非鱼（Oreochromis niloticus）作为实验对象,研究DEHP（50mg/kg bw）作用下罗非鱼肝脏组织内转录组的响应特征.利用IlluminaTM HiSeq 4000测序平台对DEHP处理组和对照组尼罗罗非鱼肝脏RNA样品分别进行转录组测序.对照组和DEHP暴露组分别获得30.10Mb和30.16Mb待分析数据（clean reads）,对转录组数据进行组装并去冗余后得到58,585个Unigene.将DEHP处理组和对照组的转录组数据进行比较一共获得5,008个差异表达基因,其中上调表达基因和下调表达基因分别为3,217个和1,791个.通过GO和KEGG功能分析后发现这些差异表达基因主要为机体免疫、生殖内分泌以及脂类代谢相关基因,这表明DEHP对尼罗罗非鱼肝脏毒性主要表现为免疫毒性、生殖毒性和脂类代谢紊乱.另外,实时荧光定量PCR验证结果发现转录组分析数据基本可靠.上述结果为在转录组水平筛选DEHP生物标志物,解析DEHP对罗非鱼毒性作用的分子机制提供了科学参考.     

Toxics Use Reduction in the Home: Lessons Learned from Household Exposure Studies

Workers and fence-line communities have been the first to benefit from the substantial reductions in toxic chemical use and byproducts in industrial production resulting from the Massachusetts Toxics Use Reduction Act (TURA). As TURA motivates reformulation of products as well as retooling of production processes, benefits could extend more broadly to large-scale reductions in everyday exposures for the general population. Household exposure studies, including those conducted by Silent Spring Institute, show that people are exposed to complex mixtures of indoor toxics from building materials and a myriad of consumer products. Pollutants in homes are likely to have multiple health effects because many are classified as endocrine disrupting compounds (EDCs), with the ability to interfere with the body’s hormone system. Product-related EDCs measured in homes include phthalates, halogenated flame retardants, and alkylphenols. Silent Spring Institute’s chemical analysis of personal care and cleaning products confirms many are potential sources of EDCs, highlighting the need for a more comprehensive toxics use reduction (TUR) approach to reduce those exposures. Toxics use reduction targeted at EDCs in consumer products has the potential to substantially reduce occupational and residential exposures. The lessons that have emerged from household exposure research can inform improved chemicals management policies at the state and national levels, leading to safer products and widespread health and environmental benefits.     

持久性、迁移性和潜在毒性化学品环境健康风险与控制研究现状及趋势分析

持久性、迁移性、毒性或高持久和高迁移性化学品(PMT/vPvM)在全球地表水、地下水和饮用水水体已被广泛检出,是未来可能显著影响人类健康和环境的一类重要新兴污染物.按照欧盟提议的鉴别标准,现有化学品中的PMT/vPvM数以千计,涉及用途广泛,包括三聚氰胺等数10种较高产量的工业化学品.PMT/vPvM可通过农田径流、工业废水和生活污水排入环境,污水处理厂目前被认为是其主要排放途径.因难以被现行常规水处理技术有效去除,PMT/vPvM可长期存在于城镇人居环境水循环系统中,危及居民饮用水及生态系统安全.欧盟已率先开始将PMT/vPvM专门纳入现行化学品风险管理体系中的优先范畴.目前,环境中仍有众多潜在PMT/vPvM,其监测方法亟待进一步完善,物质鉴定、类别范围及清单建立均尚需时日;PMT/vPvM在全球各地区的环境分布和暴露研究十分有限,其潜在、长期的生态毒性和人体健康危害效应研究较为匮乏.与此同时,替代品或替代技术以及污水处理、污染场地修复等环境工程治理技术的研究和开发,都将成为未来PMT/vPvM风险科学研究与管理决策的迫切需求.     

Exposure to endocrine disrupting chemicals perturbs lipid metabolism and circadian rhythms

A growing body of evidence indicates that exposure to environmental chemicals can contribute to the etiology of obesity by inappropriately stimulating adipogenesis as well as perturbing lipid metabolism and energy balance. One potential mechanism by which chemical exposure can influence lipid metabolism is through disturbance of circadian rhythms, endogenously-driven cycles of roughly 24hr in length that coordinate biochemical, physiological, and behavioral processes in all organisms. Here we show for the first time that exposure to endocrine disrupting compounds (EDCs), including the pesticide tributyltin, two commercial flame retardants, and a UV-filter chemical found in sunscreens, can perturb both circadian clocks and lipid metabolism in vertebrates. Exposure of developing zebrafish to EDCs affects core clock activity and leads to a remarkable increase in lipid accumulation that is reminiscent of the effects observed for longdaysin, a known disruptor of circadian rhythms. Our data reveal a novel obesogenic mechanism of action for environmental chemicals, an observation which warrants further research. Because circadian clocks regulate a wide variety of physiological processes, identification of environmental chemicals capable of perturbing these systems may provide important insights into the development of environmentally-induced metabolic disease.