Endocrine disruptors (Austin, Tex.)最新文献

{"title":"Rapid, nongenomic signaling effects of several xenoestrogens involved in early- vs. late-stage prostate cancer cell proliferation","authors":"L. Koong, C. Watson","doi":"10.4161/23273747.2014.995003","DOIUrl":"https://doi.org/10.4161/23273747.2014.995003","url":null,"abstract":"Xenoestrogens (XEs) are exogenous mimics capable of binding to estrogen receptors (ERs), competing with/disrupting the actions of physiological estrogens, and promoting tumor growth in the prostate and other endocrine tissues. Humans are exposed to numerous XEs including environmental contaminants such as plastics monomer bisphenol A (BPA), and dietary phytoestrogens such as coumestrol and genistein from soy, and resveratrol, highest in red grapes. There is growing interest in the ability of phytoestrogens to prevent or treat tumors. We previously reported that multiple cellular mechanisms influence the number of prostate cancer cells after estradiol or diethylstilbestrol treatment. We now examine the effect of these XEs on signaling mechanisms that alter the number of LAPC-4 (androgen-dependent) and PC-3 (androgen-independent) cells at environment- and diet-relevant concentrations. Coumestrol and genistein both increased the number of LAPC-4 and PC-3 cells dramatically. Rapid alterations of phospho- and total-cyclin D1 levels most closely correlated with the XE-induced changes in cell numbers. Sustained activation (phosphorylation) of the extracellular signal-regulated kinases 1 and 2 as a prelude to generation of reactive oxygen species also partially contributed to the XE's effects on cell numbers. Early-stage cells expressed higher levels of all 3 ERs (including those in membranes) than did late-stage cells; ER subtypes were variably involved in the signaling responses. Taken together, these results show that each XE can elicit its own signature constellation of signaling responses, highlighting the importance of managing exposures to both environmental and dietary XEs for existing prostate tumors. These mechanisms may offer new cellular targets for therapy.","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/23273747.2014.995003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70554959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential androgenic effects of urban sewage sludge in male rats","authors":"João Fl Luvizutto, Marize de Lm Solano, M. F. Martinez, Carla Db Fernandez, Gisela de A. Umbuzeiro, J. L. de Camargo","doi":"10.1080/23273747.2015.1066656","DOIUrl":"https://doi.org/10.1080/23273747.2015.1066656","url":null,"abstract":"The processing of urban sewage by waste water treatment plants produces a pasty mixture of complex organic materials (microorganisms, plants, chemical contaminants) and inorganic (minerals, metals, etc.) known as sewage sludge (SS). Facing the possibility of using this mixture for agricultural soil enrichment this study was designed to assess in vivo the potential endocrine disrupting activity of a SS sample using pubertal male Wistar rats or weanling rats in a modified Hershberger assay. Pubertal male rats (42-days old) were exposed ad libitum through adulthood (98-days old) to a diet containing 0, 2500, 5000, 10000 or 20000 ppm of SS. In another study, weanling male rats (21-days old) were treated daily for 10 d by gavage with flutamide (anti-androgenic positive control), testosterone propionate s.c. (androgenic positive control), or SS at 10000 and 20000 ppm in the diet. Despite no alterations in body and reproductive organs weights, diet consumption or sperm count, SS treatment impaired the sperm quality of pubertal rats, as indicated by a decreased proportion of sperm showing progressive movement. No evidence of SS-induced adverse effects was found in weanling rats. The treatments did not induce direct androgenic effects in both life periods studied in rats. However, the observed impaired sperm motility in the SS-treated pubertal rats raises some concern about the use of this material as soil additive, or in other applications where human and animals are potentially exposed.","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23273747.2015.1066656","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60058984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Human Health Risk to Endocrine Disrupting Chemicals: a Focus on Prenatal Exposures and Oxidative Stress.","authors":"Kari Neier,&nbsp;Elizabeth H Marchlewicz,&nbsp;Dana C Dolinoy,&nbsp;Vasantha Padmanabhan","doi":"10.1080/23273747.2015.1069916","DOIUrl":"https://doi.org/10.1080/23273747.2015.1069916","url":null,"abstract":"<p><p>Understanding the health risk posed by endocrine disrupting chemicals (EDCs) is a challenge that is receiving intense attention. The following study criteria should be considered to facilitate risk assessment for exposure to EDCs: 1) characterization of target health outcomes and their mediators, 2) study of exposures in the context of critical periods of development, 3) accurate estimates of human exposures and use of human-relevant exposures in animal studies, and 4) cross-species comparisons. In this commentary, we discuss the importance and relevance of each of these criteria in studying the effects of prenatal exposure to EDCs. Our discussion focuses on oxidative stress as a mediator of EDC-related health effects due to its association with both EDC exposure and health outcomes. Our recent study (Veiga-Lopez et al. 2015)¹ addressed each of the four outlined criteria and demonstrated that prenatal bisphenol-A exposure is associated with oxidative stress, a risk factor for developing diabetes and cardiovascular diseases in adulthood.</p>","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23273747.2015.1069916","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34523979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive and developmental effects of tributyltin, bisphenol A, and 17 β-estradiol in pale anemones (Aiptasia pallida)","authors":"Heather A Thorn, J. Quinn, A. Roark","doi":"10.1080/23273747.2015.1030062","DOIUrl":"https://doi.org/10.1080/23273747.2015.1030062","url":null,"abstract":"The effects of exposure to estrogenic endocrine-disrupting chemicals in most clades of marine invertebrates are unknown. The purpose of this study was to determine if exposure to 3 such chemicals modulates asexual reproduction and development in pale anemones (Aiptasia pallida). Anemones (n = 18 in each group) were exposed for 21 days to one of 8 treatments: seawater alone, seawater containing vehicle, or seawater containing a low (environmentally relevant) or high dose of tributyltin (TBT), bisphenol A (BPA), or 17 β-estradiol (E2) dissolved in vehicle. The number of asexually generated pedal lacerates produced by each anemone and the number of days required for each lacerate to develop a stomodeum and tentacles were recorded. At the end of the study, parent anemones were homogenized, and total protein content (as a proxy for body size) was quantified by Bradford assay. The roles of chemical treatment and parent anemone size in determining lacerate production were evaluated with binomial-Poisson hurdle models, and their roles in determining development rate were evaluated with generalized linear models. Application of model selection criteria suggested that exposure to E2 (at 45 ng/L) but not to TBT or BPA was associated with increased pedal lacerate production. Neither low nor high doses of any chemical tested affected the number of days required for lacerates to develop into juveniles. Although cnidarians are not thought to express genes homologous to vertebrate estrogen receptors, evidence from this and other studies suggests that estrogens, at least at high doses, are bioactive in these basal metazoans.","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23273747.2015.1030062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60058852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary phthalate metabolite concentrations among men with inflammatory bowel disease on mesalamine therapy.","authors":"Elizabeth J Hait,&nbsp;Antonia M Calafat,&nbsp;Russ Hauser","doi":"10.4161/endo.25066","DOIUrl":"https://doi.org/10.4161/endo.25066","url":null,"abstract":"<p><strong>Background: </strong>Phthalates, a family of compounds used in a variety of consumer products, are reproductive and developmental toxicants in experimental animals. One of these phthalates, dibutyl phthalate (DBP), is an inactive ingredient in the coating of Asacol.</p><p><strong>Aim: </strong>To determine if men with inflammatory bowel disease taking Asacol have higher urinary concentrations of monobutyl phthalate (MBP), a metabolite of DBP, compared to the general population in the United States.</p><p><strong>Methods: </strong>Five patients at the Massachusetts General Hospital Crohn's and Colitis Center, taking at least 800 mg of Asacol three times a day, provided one spot urine sample. Urinary MBP and other phthalate metabolite concentrations were measured by using online solid phase extraction coupled with isotope dilution high-performance liquid chromatography tandem mass spectrometry.</p><p><strong>Results: </strong>In four of the five men, the urinary concentrations of MBP (9888 ng/mL, 12,308 ng/mL, 10,124 ng/mL, and 41,590 ng/mL) and of a minor DBP metabolite, mono(3-carboxypropyl) phthalate (MCPP, 116.4 ng/mL, 163.4 ng/mL 72.6 ng/mL, 5604 ng/mL) were orders of magnitude higher than the background concentrations among the US general population. One subject missed his morning Asacol dose and had urinary MBP concentrations (17.5 ng/mL) similar to background levels.</p><p><strong>Conclusion: </strong>We confirmed that men with inflammatory bowel disease taking Asacol have urinary concentrations of MBP and MCPP much higher than background levels.</p>","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/endo.25066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32810704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PBDE metabolite 6-OH-BDE 47 affects melanin pigmentation and THRβ MRNA expression in the eye of zebrafish embryos.","authors":"Wu Dong,&nbsp;Laura J Macaulay,&nbsp;Kevin Wh Kwok,&nbsp;David E Hinton,&nbsp;P Lee Ferguson,&nbsp;Heather M Stapleton","doi":"10.4161/23273739.2014.969072","DOIUrl":"https://doi.org/10.4161/23273739.2014.969072","url":null,"abstract":"<p><p>Polybrominated diphenyl ethers and their hydroxyl-metabolites (OH-BDEs) are commonly detected contaminants in human serum in the US population. They are also considered to be endocrine disruptors, and are specifically known to affect thyroid hormone regulation. In this study, we investigated and compared the effects of a PBDE and its OH-BDE metabolite on developmental pathways regulated by thyroid hormones using zebrafish as a model. Exposure to 6-OHBDE 47 (10-100 nM), but not BDE 47 (1-50 μM), led to decreased melanin pigmentation and increased apoptosis in the retina of zebrafish embryos in a concentration-dependent manner in short-term exposures (4 - 30 hours). Six-OH-BDE 47 exposure also significantly decreased thyroid hormone receptor β (THRβ) mRNA expression, which was confirmed using both RT-PCR and in situ hybridization (whole mount and paraffin- section). Interestingly, exposure to the native thyroid hormone, triiodothyronine (T3) also led to similar responses: decreased THRβ mRNA expression, decreased melanin pigmentation and increased apoptosis, suggesting that 6-OH-BDE 47 may be acting as a T3 mimic. To further investigate short-term effects that may be regulated by THRβ, experiments using a morpholino gene knock down and THRβ mRNA over expression were conducted. Knock down of THRβ led to decreases in melanin pigmentation and increases in apoptotic cells in the eye of zebrafish embryos, similar to exposure to T3 and 6-OH-BDE 47, but THRβ mRNA overexpression rescued these effects. Histological analysis of eyes at 22 hpf from each group revealed that exposure to T3 or to 6-OH-BDE 47 was associated with a decrease of melanin and diminished proliferation of cells in layers of retina near the choroid. This study suggests that 6-OH-BDE 47 disrupts the activity of THRβ in early life stages of zebrafish, and warrants further studies on effects in developing humans.</p>","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/23273739.2014.969072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33127652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing the actions of endocrine disrupting compounds through genetic approaches in zebrafish","authors":"Daniel A. Gorelick, M. Halpern","doi":"10.4161/23273747.2014.975547","DOIUrl":"https://doi.org/10.4161/23273747.2014.975547","url":null,"abstract":"Endocrine disrupting compounds (EDCs) are a persistent threat to human and animal health. Detecting these agents and identifying their basic mechanisms of action is crucial to determining their impact. However, defining the differing effects of EDCs and their sites of activity, such as why some tissues are more sensitive than others, is a challenging endeavor. The zebrafish (Danio rerio) is a powerful genetic model that can provide unique insights into these issues. New tools for transgenesis and genome editing are enabling the identification of specific proteins and receptors that mediate the response to EDC exposure. We outline how transgenic reporters that detect EDCs and targeted mutations against their receptors or downstream effectors make zebrafish an especially favorable system for toxicological research.","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/23273747.2014.975547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70554379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autistic-like traits in Lewis rats exposed perinatally to a mixture of common endocrine disruptors","authors":"Stéphanie Degroote, D. Hunting, G. Sébire, L. Takser","doi":"10.4161/23273747.2014.976123","DOIUrl":"https://doi.org/10.4161/23273747.2014.976123","url":null,"abstract":"Epidemiological data suggest that prenatal exposure to either phthalates or flame retardants can affect mental and motor development, and can provoke internalizing behavior and attention deficit. We hypothesize that simultaneous exposure in utero to several environmental endocrine disruptors such as phthalates and flame retardants at low doses impairs brain development and leads to behavioral traits similar to those observed in Autism Spectrum Disorders (ASD). To characterize behavior relevant to ASD and common co-morbidities such as ADHD (Attention Deficit Hyperactivity Disorder) rat offspring were exposed perinatally to a mixture of phthalates and flame retardants (DEHP, DBP, DiNP, BDE-47, BDE-99) at low doses. Pregnant Lewis rats were divided into 3 groups: negative control; exposed to the mixture of endocrine disruptors; and a positive control for ASD, valproic acid, an antiepileptic drug known to cause autism in humans. Following perinatal exposure by daily gavage, behavioral tests were administered to offspring: nest-seeking behavior, auditory startle reflex, open field, elevated plus maze, and a test of social interactions. Offspring exposed to the mixture of phthalates and PBDEs showed hyperactivity, and the males had lower maternal bonding and reduced social interactions. In addition, both males and females from the exposure group showed a remarkable escaping behavior, not present in the other groups. Exposure to low doses of phthalates and flame retardants provokes behavioral alterations consistent with certain autistic- and ADHD-like traits.","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/23273747.2014.976123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70554729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dioxin relative effect potencies calculated from human thyroid data","authors":"T. Trnovec","doi":"10.4161/endo.27904","DOIUrl":"https://doi.org/10.4161/endo.27904","url":null,"abstract":"We have recently published a paper1 on derivation of relative effect potencies (REPs) of a group of potent endocrine-active chemicals, the dioxin-like compounds (DLCs). The toxic equivalency factors (TEFs), assigned on the basis of the REPs, are an important component in the risk assessment of DLCs human exposures. At present, this concept is based mainly on in vivo animal experiments using oral dosage. Consequently, the current human TEFs derived from mammalian experiments are applicable only for exposure situations in which oral ingestion occurs. Nevertheless, these “intake” TEFs are commonly—but incorrectly—used by regulatory authorities to calculate “systemic” toxic equivalents (TEQs) based on human blood and tissue concentrations, which are used as biomarkers for either exposure or effect. We sought to determine REPs for systemic human concentrations of dioxin-like mixture components using thyroid volume or serum-free thyroxine (FT4) concentration as the outcomes of interest. We used a benchmark concentration and a regression-based approach to compare the strength of association between each DLC and the thyroid end points in 320 adults residing in an organochlorine-polluted area of eastern Slovakia. We found that REPs calculated from thyroid volume and FT4 were similar. The regression coefficient (β)-derived REP data from thyroid volume and FT4 level were correlated with the World Health Organization (WHO) TEF values (Spearman r = 0.69, P = 0.01 and r = 0.62, P = 0.03, respectively). The calculated REPs were mostly within the minimum and maximum values for in vivo REPs derived by other investigators (Haws et al. 2006). We concluded that our REPs calculated from thyroid end points realistically reflect human exposure scenarios because they are based on chronic, low-dose human exposures and on biomarkers reflecting body burden. Compared with previous results, our REPs suggest higher sensitivity to the effects of DLCs.","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/endo.27904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70627793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational bisphenol A exposure and testis development.","authors":"Cecilia Williams,&nbsp;Maria Bondesson,&nbsp;Dimitry N Krementsov,&nbsp;Cory Teuscher","doi":"10.4161/endo.29088","DOIUrl":"https://doi.org/10.4161/endo.29088","url":null,"abstract":"<p><p>Virtually all humans are exposed to bisphenol A (BPA). Since BPA can act as a ligand for estrogen receptors, potential hazardous effects of BPA should be evaluated in the context of endogenous estrogenic hormones. Because estrogen is metabolized in the placenta, developing fetuses are normally exposed to very low endogenous estrogen levels. BPA, on the other hand, passes through the placenta and might have distinct adverse consequences during the sensitive stages of fetal development. Testicular gametogenesis and steroidogenesis begin early during fetal development. These processes are sensitive to estrogens and play a role in determining the number of germ stem cells, sperm count, and male hormone levels in adulthood. Although studies have shown a correlation between BPA exposure and perturbed reproduction, a clear consensus has yet to be established as to whether current human gestational BPA exposure results in direct adverse effects on male genital development and reproduction. However, studies in animals and in vitro have provided direct evidence for the ability of BPA exposure to influence male reproductive development. This review discusses the current knowledge of potential effects of BPA exposure on male reproductive health and whether gestational exposure adversely affects testis development.</p>","PeriodicalId":90159,"journal":{"name":"Endocrine disruptors (Austin, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/endo.29088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33898370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}