The Antiestrogens Tamoxifen and Fulvestrant Abolish Estrogenic Impacts of 17α-ethinylestradiol on Male Calling Behavior of Xenopus laevis

Various synthetic chemicals released to the environment can interfere with the endocrine system of vertebrates. Many of these endocrine disrupting compounds (EDCs) exhibit estrogenic activity and can interfere with sexual development and reproductive physiology. More recently, also chemicals with different modes of action (MOAs), such as antiestrogenic, androgenic and antiandrogenic EDCs, have been shown to be present in the environment. However, to date EDC-research primarily focuses on exposure to EDCs with just one MOA, while studies examining the effects of simultaneous exposure to EDCs with different MOAs are rare, although they would reflect more real, natural exposure situations. In the present study the combined effects of estrogenic and antiestrogenic EDCs were assessed by analyzing the calling behavior of short-term exposed male Xenopus laevis. The estrogenic 17α-ethinylestradiol (EE2), and the antiestrogenic EDCs tamoxifen (TAM) and fulvestrant (ICI) were used as model substances. As previously demonstrated, sole EE2 exposure (10−10 M) resulted in significant alterations of the male calling behavior, including altered temporal and spectral parameters of the advertisement calls. Sole TAM (10−7 M, 10−8 M, 10−10 M) or ICI (10−7 M) exposure, on the other hand, did not affect any of the measured parameters. If frogs were co-exposed to EE2 (10−10 M) and TAM (10−7 M) the effects of EE2 on some parameters were abolished, but co-exposure to EE2 and ICI (10−7 M) neutralized all estrogenic effects. Thus, although EDCs with antiestrogenic MOA might not exhibit any effects per se, they can alter the estrogenic effects of EE2. Our observations demonstrate that there is need to further investigate the combined effects of EDCs with various, not only opposing, MOAs as this would reflect realistic wildlife situations.     

Adipocytes under assault: Environmental disruption of adipose physiology

The burgeoning obesity epidemic has placed enormous strains on individual and societal health mandating a careful search for pathogenic factors, including the contributions made by endocrine disrupting chemicals (EDCs). In addition to evidence that some exogenous chemicals have the capacity to modulate classical hormonal signaling axes, there is mounting evidence that several EDCs can also disrupt metabolic pathways and alter energy homeostasis. Adipose tissue appears to be a particularly important target of these metabolic disruptions. A diverse array of compounds has been shown to alter adipocyte differentiation, and several EDCs have been shown to modulate adipocyte physiology, including adipocytic insulin action and adipokine secretion. This rapidly emerging evidence demonstrating that environmental contaminants alter adipocyte function emphasizes the potential role that disruption of adipose physiology by EDCs may play in the global epidemic of metabolic disease. Further work is required to better characterize the molecular targets responsible for mediating the effects of EDCs on adipose tissue. Improved understanding of the precise signaling pathways altered by exposure to environmental contaminants will enhance our understanding of which chemicals pose a threat to metabolic health and how those compounds synergize with lifestyle factors to promote obesity and its associated complications. This knowledge may also improve our capacity to predict which synthetic compounds may alter energy homeostasis before they are released into the environment while also providing critical evidentiary support for efforts to restrict the production and use of chemicals that pose the greatest threat to human metabolic health. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.     

Effects of 4-n-nonylphenol and 17beta-oestradiol on early development of the barnacle Elminius modestus

Pollutants that are present in the aquatic environment and cause abnormal endocrine function in wildlife populations have been termed endocrine disrupting chemicals (EDCs). The impacts of these chemicals on the reproduction and development of vertebrates has been shown to be significant in both field studies and laboratory experiments. Over the past decade the number of investigations into the impacts of EDCs that affect reproductive and sexual characteristics (reproductive EDCs) has increased and evidence of their potency is evident in numerous wildlife species and through data from in vitro tests. However, little information is available on whether chemicals which act as EDCs in vertebrate species affect aquatic invertebrates. The case of imposex in archeogastropods following exposure to tributyltin (TBT) is a notable exception. Moreover, a number of studies have shown that development, fecundity and reproductive output of some aquatic invertebrates are affected significantly by exposure to pollutants. In order to determine whether external signs of exposure to vertebrate EDCs can be observed and monitored in invertebrate species, we exposed larvae of the barnacle Elminius modestus to environmentally realistic concentrations of the xeno-oestrogen, 4-n-nonylphenol (NP), and the natural oestrogen, 17beta-oestradiol (E(2)). Early life stages (nauplii and cyprids) were also exposed in the laboratory to determine whether there were effects on the timing of larval development and settlement. Ovary development and size of juveniles was measured following chronic exposure. Exposure to NP in the concentration range 0.01-10 μg l(-1) resulted in disruption of the timing of larval development. Similar results were obtained with E(2). Pulse exposures showed that the timing of exposure is critical and exposures for a period of 12 months caused long-term effects. A linear, concentration-dependent response was not evident.     

Identification of endocrine disrupting chemicals acting on human aromatase

Human aromatase is the cytochrome P450 catalysing the conversion of androgens into estrogens playing a key role in the endocrine system. Due to this role, it is likely to be a target of the so-called endocrine disrupting chemicals, a series of compounds able to interfere with the hormone system with toxic effects. If on one side the toxicity of some compounds such as bisphenol A is well known, on the other side the toxic concentrations of such compounds as well as the effect of the many other molecules that are in contact with us in everyday life still need a deep investigation. The availability of biological assays able to detect the interaction of chemicals with key molecular targets of the endocrine system represents a possible solution to identify potential endocrine disrupting chemicals.Here the so-called alkali assay previously developed in our laboratory is applied to test the effect of different compounds on the activity of human aromatase. The assay is based on the detection of the alkali product that forms upon strong alkali treatment of the NADP⁺ released upon enzyme turnover. Here it is applied on human aromatase and validated using anastrozole and sildenafil as known aromatase inhibitors. Out of the small library of compounds tested, resveratrol and ketoconazole resulted to inhibit aromatase activity, while bisphenol A and nicotine were found to exert an inhibitory effect at relatively high concentrations (100 μM), and other molecules such as lindane and four plasticizers did not show any significant effect. These data are confirmed by quantification of the product estrone in the same reaction mixtures through ELISA.Overall, the results show that the alkali assay is suitable to screen for molecules that interfere with aromatase activity. As a consequence it can also be applied to other molecular targets of EDCs that use NAD(P)H for catalysis in a high throughput format for the fast screening of many different compounds as endocrine disrupting chemicals. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.     

Endocrine disrupting chemicals and disease susceptibility

Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products--including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption.     

The effects of endocrine disruptors on the male germline: an intergenerational health risk

Environmental pollution is becoming one of the major concerns of society. Among the emerging contaminants, endocrine-disrupting chemicals (EDCs), a large group of toxicants, have been the subject of many scientific studies. Besides the capacity of these compounds to interfere with the endocrine system, they have also been reported to exert both genotoxic and epigenotoxic effects. Given that spermatogenesis is a coordinated process that requires the involvement of several steroid hormones and that entails deep changes in the chromatin, such as DNA compaction and epigenetic remodelling, it could be affected by male exposure to EDCs. A great deal of evidence highlights that these compounds have detrimental effects on male reproductive health, including alterations to sperm motility, sexual function, and gonad development. This review focuses on the consequences of paternal exposure to such chemicals for future generations, which still remain poorly known. Historically, spermatozoa have long been considered as mere vectors delivering the paternal haploid genome to the oocyte. Only recently have they been understood to harbour genetic and epigenetic information that plays a remarkable role during offspring early development and long-term health. This review examines the different modes of action by which the spermatozoa represent a key target for EDCs, and analyses the consequences of environmentally induced changes in sperm genetic and epigenetic information for subsequent generations.     

Endocrine disruptors and female fertility: Focus on (bovine) ovarian follicular physiology

Throughout the previous century, the production, use and, as a result, presence of chemicals in the environment increased enormously. Consequently, humans and animals are exposed to a wide variety of chemical substances of which some possess the ability to disrupt the endocrine system in the body, thereby denominated as “endocrine disrupting chemicals” (EDCs) or “endocrine disruptors”. Because the reproductive system is a target organ for endocrine disruption, EDCs are postulated as one of the possible causes of human subfertility. Within the reproductive system, the ovarian follicle can be considered as an extremely fragile microenvironment where interactions between the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In this review, we explore how EDCs can interfere with the well-balanced conditions in the ovarian follicle. In addition, we highlight the bovine ovarian follicle as an alternative in vitro model for EDC and broader toxicology research.     

Endocrine disruptors: present issues, future directions

A variety of natural products and synthetic chemicals, known collectively as endocrine-disrupting compounds (EDCs), mimic or interfere with the mechanisms that govern vertebrate reproductive development and function. At present, research has focused on (i) the morphological and functional consequences of EDCs; (ii) identifying and determining the relative potencies of synthetic and steroidal compounds that have endocrine-disrupting effects; (iii) the mechanism of action of EDCs at the molecular level; and (iv) the recognition that in "real life," contamination usually reflects mixtures of EDCs. Future research must examine (i) the interactive nature of EDCs, particularly whether the threshold concept as developed in traditional toxicological research applies to these chemicals; (ii) when and how EDCs act at the physiological level, particularly how they may organize the neural substrates of reproductive physiology and behavior; (iii) the various effects these compounds have on different species, individuals, and even tissues; and (iv) how adaptations may evolve in natural populations with continued exposure to EDCs. Several predictions are offered that reflect these new perspectives. Specifically, (i) the threshold assumption will be found not to apply to EDCs because they mimic the actions of endogenous molecules (e.g., estrogen) critical to development; hence, the threshold is automatically exceeded with exposure. (ii) Behavior can compound and magnify the effects of EDCs over successive generations; that is, bioaccumulated EDCs inherited from the mother not only influence the morphological and physiological development of the offspring but also the offsprings' reproductive behavior as adults. This adult behavior, in turn, can have further consequences on the sexual development of their own young. (iii) The sensitivity of a species or an individual to a compound is related to species (individual)-typical concentrations of circulating gonadal steroid hormones. Related to this is the recent finding that alternate forms of the putative receptors are differentially distributed, thereby contributing to the different effects that have been observed. (iv) Except in extraordinary situations, populations often continue to exist in contaminated sites. One possible explanation for this observation that needs to be considered is that animals can rapidly adapt to the nature and level of contamination in their environment. It is unlikely that successive generations coincidentally become insensitive to gonadal steroid hormones fundamentally important as biological regulators of development and reproduction. Rather, adaptive alterations in the genes that encode steroid receptors may occur with chronic exposure to EDCs, allowing the sex hormone receptor to discriminate natural steroids from EDCs.     

Development of comparative methods using gas chromatography-mass spectrometry and capillary electrophoresis for determination of endocrine disrupting chemicals in bio-solids

Two analytical separation techniques are being investigated for their potential in determining a wide range of endocrine disrupting chemicals (EDCs) in the environment. Capillary electrophoresis (CE) in the micellar mode in conjunction with a cyclodextrin (CD) modifier is shown to have potential for determination of alkylphenol breakdown products. Gas chromatography with mass spectrometric (GC-MS) detection is being utilised for validation of the CE method development and in addition as a separation technique to optimise preconcentration using solid-phase extraction. GC has demonstrated potential for the separation of 26 priority chemicals suspected as being endocrine disrupting compounds. The challenge of the method development process lies in the fact that these compounds are of differing polarities, size and charge and therefore are difficult to separate in a single run. Capillary electrophoresis in the CD-MEKC (micellar electrokinetic chromatography) mode is showing potential in this regard. Limits of determination are in the low mg/l range for CE and GC, however, using preconcentration it is possible to improve detection sensitivity with >80% recovery for some analytes and up to 100% recovery for most target species.     

Non-traditional targets of endocrine disrupting chemicals: the roots of hormone signaling

The topic of endocrine disruption and the broad range of physiologicaleffects caused by endocrine disrupting chemicals (EDCs) canonly be meaningfully framed within an ecological and evolutionarycontext. Environmental pollutants and EDCs operate by disruptingthe "chemical communication" that coordinates signaling withinan organism. Here we discuss how EDCs are also able to disruptthe chemical communication between plants and soil bacterianecessary for initiating nitrogen-fixing symbiosis. We alsoexamine, through examples of pollutant-related impacts on awide range of invertebrates, the need for identifying emergingtargets of EDCs. We suggest broadening the defined field ofendocrine disruption to encompass the effects of synthetic chemicalsthat interfere with signaling and communication, not only withinan organism, but also between organisms and linking ecosystems.The ecological consequences of failing to recognize novel targetsof chemical pollutants and EDCs may be a net loss of biologicaldiversity and a further imbalance of the global nitrogen cycle.     

Endocrine Toxicants and Reproductive Success in Fish

There is compelling evidence on a global scale for compromised growth and reproduction, altered development, and abnormal behaviour in feral fish that can be correlated or in some cases causally linked with exposure to endocrine disrupting chemicals (EDCs). Attributing cause and effect relationships for EDCs is a specific challenge for studies with feral fish as many factors including food availability, disease, competition and loss of habitat also affect reproduction and development. Even in cases where there are physiological responses of fish exposed to EDCs (e.g., changes in reproductive hormone titres, vitellogenin levels), the utility of these measures in extrapolating to whole animal reproductive or developmental outcomes is often limited. Although fish differ from other vertebrates in certain aspects of their endocrinology, there is little evidence that fish are more sensitive to the effects of EDCs. Therefore, to address why endocrine disruption seems so widespread in fish, it is necessary to consider aspects of fish physiology and their environment that may increase their exposure to EDCs. Dependence on aquatic respiration, strategies for iono-osmotic regulation, and maternal transfer of contaminants to eggs creates additional avenues by which fish are exposed to EDCs. This paper provides an overview of responses observed in feral fish populations that have been attributed to EDCs and illustrates many of the factors that need consideration in evaluating the risks posed by these chemicals.     

Environmental Endocrine Disruptors Promote Adipogenesis in the 3T3‐L1 Cell Line through Glucocorticoid Receptor Activation

The burgeoning obesity and diabetes epidemics threaten health worldwide, yet the molecular mechanisms underlying these phenomena are incompletely understood. Recently, attention has focused on the potential contributions of environmental pollutants that act as endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases. Because glucocorticoid signaling is central to adipocyte differentiation, the ability of EDCs to stimulate the glucocorticoid receptor (GR) and drive adipogenesis was assessed in the 3T3‐L1 cell line. Various EDCs were screened for glucocorticoid‐like activity using a luciferase reporter construct, and four (bisphenol A (BPA), dicyclohexyl phthalate (DCHP), endrin, and tolylfluanid (TF)) were shown to significantly stimulate GR without significant activation of the peroxisome proliferator‐activated receptor‐γ. 3T3‐L1 preadipocytes were then treated with EDCs and a weak differentiation cocktail containing dehydrocorticosterone (DHC) in place of the synthetic dexamethasone. The capacity of these compounds to promote adipogenesis was assessed by quantitative oil red O staining and immunoblotting for adipocyte‐specific proteins. The four EDCs increased lipid accumulation in the differentiating adipocytes and also upregulated the expression of adipocytic proteins. Interestingly, proadipogenic effects were observed at picomolar concentrations for several of the EDCs. Because there was no detectable adipogenesis when the preadipocytes were treated with compounds alone, the EDCs are likely promoting adipocyte differentiation by synergizing with agents present in the differentiation cocktail. Thus, EDCs are able to promote adipogenesis through the activation of the GR, further implicating these compounds in the rising rates of obesity and diabetes.     

Monitoring Endocrine Disrupter Compounds in the Tunisian Hamdoun River using In Vitro Bioassays

Anthropogenic chemicals occurring in the environment, namely endocrine-disrupting chemicals (EDCs), have generated growing concern over their potential adverse effects on human wildlife health and ecosystem processes. This interest resulted particularly from their abilities to mimic the effect of endogenous hormones. In this study, we used stable transfected reporter cell lines to investigate the endocrine-disrupting profile of water as well as sediment samples. Samples are collected from up- and downstream of an industrial wastewater discharge point at the Hamdoun River in the vicinity of an industrial zone located at the center of Tunisia. The analysis of estrogen, androgen, and xenobiotic (pregnane X and dioxin) ligands receptors expressed by chimeric cell lines indicated that while the water and sediment samples from upstream sites have lower levels of estrogenic activity, those from downstream exhibited stronger estrogenic, aryl hydrocarbon receptor (AhR), and Pregnane X Receptor (PXR) activities. Moreover, collected samples have shown hormonal activity in terms of all tested receptors except the androgenic ones. In vitro recombinant estrogen receptor competitive binding assays revealed that while the estrogenic activities of the downstream water sample compounds had a strong affinity for estrogen receptor α (ERα), those present in the sediment samples showed a weaker one. These findings were consolidated by subsequent chemical analysis (high-performance liquid chromatography with UV detectors). Our results indicate that the water and sediment discharges at the Hamdoun River represent a major sink for EDCs from natural and industrial effluents, particularly those of the textile industry, with pernicious potential to disrupt normal endocrine functions.     

Molecular mechanism(s) of endocrine‐disrupting chemicals and their potent oestrogenicity in diverse cells and tissues that express oestrogen receptors

Endocrine‐disrupting chemicals (EDCs) are natural or synthetic compounds present in the environment which can interfere with hormone synthesis and normal physiological functions of male and female reproductive organs. Most EDCs tend to bind to steroid hormone receptors including the oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR). As EDCs disrupt the actions of endogenous hormones, they may induce abnormal reproduction, stimulation of cancer growth, dysfunction of neuronal and immune system. Although EDCs represent a significant public health concern, there are no standard methods to determine effect of EDCs on human beings. The mechanisms underlying adverse actions of EDC exposure are not clearly understood. In this review, we highlighted the toxicology of EDCs and its effect on human health, including reproductive development in males and females as shown in in vitro and in vivo models. In addition, this review brings attention to the toxicity of EDCs via interaction of genomic and non‐genomic signalling pathways through hormone receptors.     

Proteomic Analysis of the Reproductive Organs of the Hermaphroditic Gastropod Lymnaea stagnalis Exposed to Different Endocrine Disrupting Chemicals

Many studies have reported perturbations of mollusc reproduction following exposure to low concentrations (ng/L range) of endocrine disrupting chemicals (EDCs). However, the mechanisms of action of these molecules on molluscs are still poorly understood. Investigation of the modifications of protein expression in organisms exposed to chemicals using proteomic methods can provide a broader and more comprehensive understanding of adverse impacts of pollution on organisms than conventional biochemical biomarkers (e.g., heat-shock proteins, metallothioneins, GST, EROD). In this study we have investigated the impacts of four chemicals, which exhibit different endocrine disrupting properties in vertebrates, on the proteome of the hermaphroditic freshwater pulmonate gastropod Lymnaea stagnalis after 21 days of exposure. Testosterone, tributyltin, chlordecone and cyproterone acetate were chosen as tested compounds as they can induce adverse effects on the reproduction of this snail. The 2D-DIGE method was used to identify proteins whose expression was affected by these compounds. In addition to modifying the expression of proteins involved in the structure and function of the cytoskeleton, chemicals had impacts on the expression of proteins involved in the reproduction of L. stagnalis. Exposure to 19.2 µg/L of chlordecone increased the abundance of ovipostatin, a peptide transmitted during mating through seminal fluid, which reduces oviposition in this species. The expression of yolk ferritin, the vitellogenin equivalent in L. stagnalis, was reduced after exposure to 94.2 ng Sn/L of tributyltin. The identification of yolk ferritin and the modification of its expression in snails exposed to chemicals were refined using western blot analysis. Our results showed that the tested compounds influenced the abundance of yolk ferritin in the reproductive organs. Alteration in proteins involved in reproductive pathways (e.g., ovipostatin and yolk ferritin) could constitute relevant evidence of interaction of EDCs with reproductive pathways that are under the control of the endocrine system of L. stagnalis.     

In Vivo Screening Using Transgenic Zebrafish Embryos Reveals New Effects of HDAC Inhibitors Trichostatin A and Valproic Acid on Organogenesis

The effects of endocrine disrupting chemicals (EDCs) on reproduction are well known, whereas their developmental effects are much less characterized. However, exposure to endocrine disruptors during organogenesis may lead to deleterious and permanent problems later in life. Zebrafish (Danio rerio) transgenic lines expressing the green fluorescent protein (GFP) in specific organs and tissues are powerful tools to uncover developmental defects elicited by EDCs. Here, we used seven transgenic lines to visualize in vivo whether a series of EDCs and other pharmaceutical compounds can alter organogenesis in zebrafish. We used transgenic lines expressing GFP in pancreas, liver, blood vessels, inner ear, nervous system, pharyngeal tooth and pectoral fins. This screen revealed that four of the tested chemicals have detectable effects on different organs, which shows that the range of effects elicited by EDCs is wider than anticipated. The endocrine disruptor tetrabromobisphenol-A (TBBPA), as well as the three drugs diclofenac, trichostatin A (TSA) and valproic acid (VPA) induced abnormalities in the embryonic vascular system of zebrafish. Moreover, TSA and VPA induced specific alterations during the development of pancreas, an observation that was confirmed by in situ hybridization with specific markers. Developmental delays were also induced by TSA and VPA in the liver and in pharyngeal teeth, resulting in smaller organ size. Our results show that EDCs can induce a large range of developmental alterations during embryogenesis of zebrafish and establish GFP transgenic lines as powerful tools to screen for EDCs effects in vivo.     

Perturbateurs endocriniens et écosystèmes

Hormonal imbalances, sexual changes and unusual behaviours are observed in wildlife. Some chemicals are implicated as endocrine disruptors (EDCs). Their dispersal into ecosphere allows them to reach biotopes isolated of emission sources and they accumulate in organisms and they cause alterations in biological functions (reprotoxicity, immunotoxicity, etc.). Beyond the individual, the community equilibrium is endangered with a potential impact on biodiversity. The organohalogen substances are historically concerned. Despite the prohibition of organochlorine pesticides and PCBs, they persist in aquatic and terrestrial habitats. But the “emerging substances” are also dangerous. Numerous examples of endocrine disruption in animal communities are described. The imposex in female of marine gastropods related to tributyltin (TBT) is one of the earliest known events. The feminization of fish in the estuary of the Seine, the hermaphroditism of some amphibians and the strange behaviour of birds, are famous facts. The cumulative effects are of concern to wild populations. These are mix of pollutants or the concomitancy of other global changes, the decline of polar bears or seals from the Baltic Sea proves it. In conclusion, endocrine disruption jeopardizes all natural biological systems and contributes in loss of biological diversity by reducing the number of sensitive species and making them vulnerable, considering the global extinction risk.     

Biodegradation of endocrine‐disrupting compounds by ligninolytic fungi: mechanisms involved in the degradation

Without any doubt, endocrine‐disrupting compounds (EDCs) represent an environmental risk for wildlife and human beings. Endocrine‐disrupting effects were found for many chemicals in products for personal use, industrial compounds and even in classical persistent organic pollutants (POPs). In order to understand the fate of EDCs in the environment, it is highly important to identify and to clarify the biodegradation mechanisms that can lead to their decomposition. Ligninolytic fungi (LF) are interesting microorganisms that are capable of participating in a variety of versatile decomposition mechanisms. The microorganisms represent a useful model group and, moreover, LF or their enzymes can be actively used for decontamination. Potential optimization of the decontamination process provides another important reason why it is necessary for understanding the mechanisms of EDC transformation. This minireview summarizes current knowledge about the LF biodegradation mechanisms of the most important micropollutants (xenoestrogens), including nonylphenols, bisphenol A and 17α‐ethinylestradiol and polychlorinated biphenyls as POPs with endocrine‐disrupting potency. Generally, LF exhibit the ability to either polymerize the target pollutants or to substantially decompose the original structure using ligninolytic enzymes and cytochrome P‐450. Moreover, most of the transformation processes are accompanied by reduction of the endocrine‐disrupting activity or ecotoxicity.     

An Integrated Approach to Assess the Role of Chemical Exposure in Obesity

The evidence that developmental exposure of humans to chemicals plays a role in onset of obesity is convincing, yet controversial as it challenges traditional views on the etiology of obesity. OBELIX, one of the largest pan‐European studies researching the obesogen hypothesis, is accruing experimental and epidemiologic data on major classes of endocrine disrupting chemicals (EDCs) in both laboratory animal and prospective human cohort studies. Though still underway, this integrated and multidisciplinary project is adding new insights to the weight of evidence for effects of EDCs on obesity. Animal studies indicate divergent sex‐specific effects of perinatal exposure on the development of overweight. In vitro mechanistic studies have shown that EDCs enhance murine adipocyte differentiation, an effect that is accompanied by global DNA demethylation. Epidemiological studies have revealed an inverse relationship between prenatal polychlorinated biphenyl exposure and birth weight, and suggest differences in pre‐ and postnatal exposure on growth trajectories in children.     

环境激素类物质对人类健康的影响

环境激素是具有生物体内分泌激素干扰作用的一大类化学物质。环境激素在环境中普遍存在,不仅对生物的繁殖具有一定影响,而且还对生物的许多行为和感知能力产生影响。论文综述了近年来国内外有关环境激素的研究进展,综合分析了环境激素对人类健康的影响,阐述了其作用机理,并探讨了环境激素类物质控制和管理途径。