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Oestrogen plays a crucial physiological role in both women and men. It regulates reproductive functions and maintains various non-reproductive tissues through its receptors, such as oestrogen receptor 1/oestrogen receptor α (ESR1/Erα), oestrogen receptor 2/oestrogen receptor β (ESR2/Erβ), and G protein-coupled oestrogen receptor 1 (GPER). This hormone is essential for the proper functioning of women's ovaries and uterus. Oestrogen supports testicular function and spermatogenesis in men and contributes to bone density, cardiovascular health, and metabolic processes in both sexes. Nuclear receptors Er-α and Er-β belong to the group of transcription activators that stimulate cell proliferation. In the environment, compounds similar in structure to the oestrogens compete with endogenous hormones for binding sites to receptors and to disrupt homeostasis. The lack of balance in oestrogen levels can lead to infertility, cancer, immunological disorders, and other conditions. Exogenous endocrine-active compounds, such as bisphenol A (BPA), phthalates, and organic phosphoric acid esters, can disrupt signalling pathways responsible for cell division and apoptosis processes. The metabolism of oestrogen and its structurally similar compounds can produce carcinogenic substances. It can also stimulate the growth of cancer cells by regulating genes crucial for cell proliferation and cell cycle progression, with long-term elevated levels linked to hormone-dependent cancers such as breast cancer. Oestrogens can also affect markers of immunological activation and contribute to the development of autoimmune diseases. Hormone replacement therapy, oral contraception, in vitro fertilisation stimulation, and hormonal stimulation of transgender people can increase the risk of breast cancer. Cortisol, similar in structure to oestrogen, can serve as a biomarker associated with the risk of developing breast cancer. The aim of this review is to analyse the sources of oestrogens and their effects on the endogenous and exogenous process of homeostasis. [ABSTRACT FROM AUTHOR]

Bisphenols are chemicals extensively used in plastic industries. Bisphenol A (BPA), a member of the bisphenol family, is widely used in manufacturing epoxy resins and polycarbonate plastic. Epoxy resins have applications in manufacturing the inside lining of metal cans to preserve the quality of canned foods. Polycarbonate plastics have a usage in the manufacture of packaging of food and drinks. BPA-containing plastic is also extensively used in the production of dental implants and sales receipts. There is constant leaching of BPA from the plastic items into the edibles stored in them, particularly when these plastic containers get exposed to high temperatures, non-neutral pH and multiple uses. On consuming these contaminated food items, the gut is the first organ exposed to BPA, followed by all other body systems. In most human body fluid samples examined, BPA is present in a detectable amount. BPA belongs to the family of known endocrine-disrupting chemicals with oestrogenic properties. The increasing alarms regarding the adverse effects of BPA on child development compelled prohibiting products that contain BPA from being used in baby care in many countries worldwide. Being a known xeno-oestrogen, BPA may target the oestrogen receptors in the gut and may affect the various actions mediated by oestrogen in the gut. Besides oestrogenic properties, BPA may have many other hormonal and non-hormonal actions that may affect gut functions. The present article reviews the studies reporting the effect of BPA on gut functions. [ABSTRACT FROM AUTHOR]

Despite significant advances in understanding nephron segment patterning, many questions remain about the underlying genes and signaling pathways that orchestrate renal progenitor cell fate choices and regulate differentiation. In an effort to identify elusive regulators of nephron segmentation, our lab conducted a high-throughput drug screen using a bioactive chemical library and developing zebrafish, which are a conserved vertebrate model and particularly conducive to large-scale screening approaches. 17β-estradiol (E2), which is the dominant form of estrogen in vertebrates, was a particularly interesting hit from this screen. E2 has been extensively studied in the context of gonad development, but roles for E2 in nephron development were unknown. Here, we report that exogenous estrogen treatments affect distal tubule composition, namely, causing an increase in the distal early segment and a decrease in the neighboring distal late. These changes were noted early in development but were not due to changes in cell dynamics. Interestingly, exposure to the xenoestrogens ethinylestradiol and genistein yielded the same changes in distal segments. Further, upon treatment with an estrogen receptor 2 (Esr2) antagonist, PHTPP, we observed the opposite phenotypes. Similarly, genetic deficiency of the Esr2 analog, esr2b, revealed phenotypes consistent with that of PHTPP treatment. Inhibition of E2 signaling also resulted in decreased expression of essential distal transcription factors, irx3b and its target irx1a. These data suggest that estrogenic compounds are essential for distal segment fate during nephrogenesis in the zebrafish pronephros and expand our fundamental understanding of hormone function during kidney organogenesis. [ABSTRACT FROM AUTHOR]

Xenoestrogens are natural or synthetic compounds that mimic the effect of endogenous estrogens and might cause cancer. We aimed to compare the global transcriptomic response to zearalenone (ZEA; mycotoxin) and bisphenol A (BPA; plastic additive) with the effect of physiological estradiol (E2) in the PEO1 human ovarian cell line by mRNA and microRNA sequencing. Estrogen exposure induced remarkable transcriptomic changes: 308, 288 and 63 genes were upregulated (log2FC > 1); 292, 260 and 45 genes were downregulated (log2FC < −1) in response to E2 (10 nM), ZEA (10 nM) and BPA (100 nM), respectively. Furthermore, the expression of 13, 11 and 10 miRNAs changed significantly (log2FC > 1, or log2FC < −1) after exposure to E2, ZEA and BPA, respectively. Functional enrichment analysis of the significantly differentially expressed genes and miRNAs revealed several pathways related to the regulation of cell proliferation and migration. The effect of E2 and ZEA was highly comparable: 407 genes were coregulated by these molecules. We could identify 83 genes that were regulated by all three treatments that might have a significant role in the estrogen response of ovarian cells. Furthermore, the downregulation of several miRNAs (miR-501-5p, let-7a-2-3p, miR-26a-2-3p, miR-197-5p and miR-582-3p) was confirmed by qPCR, which might support the proliferative effect of estrogens in ovarian cells. [ABSTRACT FROM AUTHOR]

In this study, a biochar obtained from poplar wood gasification at a temperature of 850 °C was used to adsorb the xenoestrogens 4-tert-octylphenol (OP) and bisphenol A (BPA) and the herbicide metribuzin from water. Scanning electron microscopy (SEM-EDX) and Fourier-transform infrared (FTIR) spectroscopy were employed to investigate the surface micromorphology and functional groups composition of biochar, respectively. The study of sorption kinetics showed that all compounds achieved the steady state in less than 2 h, according to a pseudo-second order model, which denoted the formation of strong bonds (chemisorption) between biochar and the compounds. Adsorption isotherms data were described by the Henry, Freundlich, Langmuir and Temkin equations. At temperatures of 10 and 30 °C, the equilibrium data of the compounds were generally better described by the Freundlich model, although, in some cases, high correlation coefficients (r ≥ 0.98) were obtained for more than one model. Freundlich constants, KF, for OP, BPA and metribuzin were, respectively, 218, 138 and 4 L g−1 at 10 °C and 295, 243 and 225 L g−1 at 30 °C, indicating a general increase of adsorption at higher temperature. Desorption of all compounds, especially OP and BPA, from biochar was slow and very scarce, denoting an irreversible and hysteretic process. Comparing the results of this study with those reported in the literature, we can conclude that the present biochar has a surprising ability to retain organic compounds almost permanently, thus behaving as an excellent low-cost biosorbent. [ABSTRACT FROM AUTHOR]

Among vertebrates, teleosts display a wide array of sex determination and differentiation mechanisms ranging from chromosomal sex determination on one end of the spectrum to environmental sex determination on the other end. However, the interplay of both these mechanisms is also not uncommon. Several gonochoristic fishes exhibit gonadal plasticity often resulting in sex reversal. The major manipulation of sex differentiation in teleost is affected by sex steroids. In this context, the increasing contamination of aquatic ecosystems by estrogen-like compounds, commonly known as xenoestrogens, is of major concern. This often leads to deleterious effects on the reproductive success of fish and thereby adversely impacts aquatic biodiversity. In the present review, we have focused on impact of xenoestrogen at different levels of the reproductive system influencing not only gonadal differentiation in teleosts but also their reproductive functions. The review would also explore the mitigation strategies and regulations in place for aquatic xenoestrogen management. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is the main ingredient of plastic materials that are the most used in the world and can cause environmental problems as a result of anthropogenic effects. It is adversely effect on organisms, especially in the degradation of the endocrine system. This study focused on short-term exposure of different BPA concentrations on two fish species (Onchorhynchus mykiss and Vimba vimba). The study configuration was prepared as a 96-h exposure design in BPA aquariums according to concentrations of 500, 1000, and 1500 μg/L. The results showed that turbidity, one of the water quality parameters, was significantly higher in BPA groups than in the control group (p<0.05). In addition, while turbidity showed an increasing trend with increasing time in the BPA group, it did not show any change for the control group. Deteriorations in fish behaviors observed such as loss of balance and high mucus secretion in BPA groups. Hematological results showed that WBC, RBC, HGB, and HCT values in O. mykiss were significantly higher in 1000 and 1500 μg/L BPA groups compared to the control (p<0.01). On the contrary, hematological parameters in V. vimba BPA groups showed similar or lower values compared to control. The current study revealed that fish in the culture environment may be adversely affected physiologically and behaviorally by BPA exposure. [ABSTRACT FROM AUTHOR]

Due to the prevalence of hypertension (one of the major risk factors of CVD) in the population, it is necessary to explore the adverse effects of daily tolerable and "safe" dose of bisphenol A (BPA) under hypertensive conditions. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME, 40 mg/kg b.w/day) induced hypertensive Wistar rats to BPA (50 μg/kg b.w/day) by oral administration along with appropriate controls for 30 days period. The results illustrate that a 'safe' dose of BPA does not influence the systolic blood pressure (SBP) and levels of circulatory biomarkers of tissue damage. On the other hand, BPA exposure significantly (p < 0.05) elevates the thiobarbituric acid reactive substances (TBARS) content in plasma and tissues (heart, aorta, liver and kidney) in hypertensive rats when compared with respective control (BPA alone exposed) rats. Similarly, a significant modulation of ROS generation in RBC, plasma nitric oxide (NO) level and angiotensin-converting enzyme (ACE) activity was observed only under hypertensive milieu. In conclusion, the observed adverse effects during 'safe' dose of BPA exposure are specific to the hypertensive condition. Therefore, a precise investigation to explore the effects of BPA exposure in vulnerable hypertensive populations is highly suggested. [ABSTRACT FROM AUTHOR]

Copyright of Advances in Biochemistry / Postepy Biochemii is the property of Polish Biochemical Society / Acta Biochimica Polonica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the last decades, oestrogenic compounds have often been reported in environmentally relevant concentrations in aquatic environments around the world. Most laboratory studies of oestrogens try to understand the effects of a single contaminant, but in natural environments, the effects may be quite different due to interactions with other compounds. The present study aimed to compare the action of oestrone (E1) and bisphenol-A (BPA), acting singularly and in combination, on the spermatogenesis of Astyanax bimaculatus. After exposure to 100 ng/L of E1, BPA and a mixture of the two for 15 days, our results showed that E1 and the E1 + BPA mixture significantly altered the number of spermatogenic cells. BPA presented high cytotoxicity when compared to other treatments. Analysis of the two oestrogenic compounds suggests that the E1 + BPA mixture has no additive or synergistic effects. Together, the results of the present study indicate that endocrine-disrupting chemicals (EDCs) analysed alone may behave differently than when administered with other substances. [ABSTRACT FROM AUTHOR]

The mammary gland is a hormone sensitive organ that is susceptible to endocrine-disrupting chemicals (EDCs) during the vulnerable periods of parous reorganization (ie, pregnancy, lactation, and involution). Pregnancy is believed to have long-term protective effects against breast cancer development; however, it is unknown if EDCs can alter this effect. We examined the long-term effects of propylparaben, a common preservative used in personal care products and foods, with estrogenic properties, on the parous mouse mammary gland. Pregnant BALB/c mice were treated with 0, 20, 100, or 10 000 µg/kg/day propylparaben throughout pregnancy and lactation. Unexposed nulliparous females were also evaluated. Five weeks post-involution, mammary glands were collected and assessed for changes in histomorphology, hormone receptor expression, immune cell number, and gene expression. For several parameters of mammary gland morphology, propylparaben reduced the effects of parity. Propylparaben also increased proliferation, but not stem cell number, and induced modest alterations to expression of ERα-mediated genes. Finally, propylparaben altered the effect of parity on the number of several immune cell types in the mammary gland. These results suggest that propylparaben, at levels relevant to human exposure, can interfere with the effects of parity on the mouse mammary gland and induce long-term alterations to mammary gland structure. Future studies should address if propylparaben exposures negate the protective effects of pregnancy on mammary cancer development. [ABSTRACT FROM AUTHOR]

Many chemicals released into the environment are believed to disrupt normal endocrine functions in humans and animals. A major group of endocrine disrupting chemicals (EDCs) that could be responsible for reproductive defects are those that mimic natural oestrogens, known as xenoestrogens. A number of in vivo and in vitro screening strategies are being developed to identify and classify xenoestrogens, in order to determine whether they pose a health risk to humans and animals. Oestrogens and androgens mediate their activity via intracellular receptors, directly in muscular tissue, as well as indirectly via stimulation of growth hormones from the pituitary glands and other growth factors from liver plus several other organs. Mancozeb is a metal ethylenebisdithiocarbamate (EBDC) fungicide used to protect many fruits and vegetables and field crops against pathogenic fungal. The T47D-KBluc, GH3.TRE-Luc and MDA-kb2 reporter gene assays were used to determine the possible endocrine disrupting activity/potential of mancozeb. No activity was detected in any of the assays and no mancozeb was detected in any of the dams either. Oestrogenic activity was detected in Albasini Dam, Nandoni Dam and Xikundu weir, but all values were below 0.7 ng l−1 trigger value for oestrogenic activity in drinking water. [ABSTRACT FROM AUTHOR]

Organohalogenated compounds contaminations in feed ingredients and feeds pose threats to the safety of food animals, and public health. Pigs are exposed through ingestions of feed contaminated with organohalogenated compounds. Microbes - organohalogens interactions in the gut cause changes in mean species diversities of bacteria, and induce gut dysbiosis. Along with metabolites from first-pass metabolisms, they affect proteins and molecular pathways that regulate ROS sensing, and induce oxidative stress. They also bind to estrogen receptors and mimic estrogen activities to impair reproductive endocrine functions. Nutritional interventions such as feed and feed ingredients substitutions, and harnessing non-conventional feed resources (NCFR) can offer sustainable alleviations. This will mitigate the risk of exposure to organohalogens whilst providing the needed nutrients to meet the animals' nutritional requirements. In addition, it will enhance the biological defense mechanisms in pigs. Phytonutrition can enhance biodegradation, and detoxification of recalcitrant organohalogenated xenobiotics. This provides a low cost, "green" strategy to alleviate adverse effects of organohalogenated xenobiotics in pigs. The low costs associated with makes this a viable remedy, especially for low income countries. [ABSTRACT FROM AUTHOR]

Background: An individual's response to environmental exposures varies depending on their genotype, which has been termed the gene-environment interaction. The phenotype of cell exposed can also be a key determinant in the response to physiological cues, indicating that a cell-gene-environment interaction may exist. We investigated whether the cellular environment could alter the transcriptional response to environmental chemicals. Publicly available gene expression array data permitted a targeted comparison of the transcriptional response to a unique subclass of environmental chemicals that alter the activity of the estrogen receptor, xenoestrogens. Results: Thirty xenoestrogens were included in the analysis, for which 426 human gene expression studies were identified. Comparisons were made for studies that met the predefined criteria for exposure length, concentration, and experimental replicates. The cellular response to the phytoestrogen genistein resulted in remarkably unique transcriptional profiles in breast, liver, and uterine cell-types. Analysis of gene regulatory networks and molecular pathways revealed that the cellular context mediated the activation or repression of functions important to cellular organization and survival, including opposing effects by genistein in breast vs. liver and uterine cell-types. When controlling for cell-type, xenoestrogens regulate unique gene networks and biological functions, despite belonging to the same class of environmental chemicals. Interestingly, the genetic sex of the cell-type also strongly influenced the transcriptional response to xenoestrogens in the liver, with only 22% of the genes significantly regulated by genistein common between male and female cells. Conclusions: Our results demonstrate that the transcriptional response to environmental chemicals depends on a variety of factors, including the cellular context, the genetic sex of a cell, and the individual chemical. These findings highlight the importance of evaluating the impact of exposure across cell-types, as the effect is responsive to the cellular environment. These comparative genetic results support the concept of a cell-gene-environment interaction. [ABSTRACT FROM AUTHOR]

This study was conducted to verify a hypothesis that immune cells are a target for the action of endocrine disrupting chemicals (EDCs) by investigating whether methylparaben (MeP) modulates human neutrophil functions. Neutrophils isolated from 15 donor samples were studied. Cells were incubated in the presence of increasing MeP concentrations (0.06, 0.8, 10, and 20 μM). The cytotoxic effect of MeP on neutrophils was evaluated by the MTT test. The ability of the neutrophils for chemotaxis, phagocytosis, NADPH oxidase activity, and superoxide anion generation was assessed in Boyden's chamber, Park's method with latex, the NBT test, and the cytochrome C reduction test, respectively. The total nitric oxide (NO) concentration was measured by the Griess reaction. There was no observable cytotoxic effect of MeP on human neutrophils. MeP (10 and 20 μM) exposure decreased neutrophilic ability for the tested functions, except for NO production. In neutrophils incubated with MeP (0.8 μM as well as 0.06 and 0.8 μM, respectively), we observed a decreased activity of NADPH oxidase as well as decreased generation of superoxide anion. Our results suggest a suppressive effect of MeP on the tested functions of human neutrophils, which confirms that immune cells are vulnerable to EDC action. Therefore, the disturbance of neutrophils' oxygen-dependent phagocytic function as a result of exposure to environmental doses of MeP action could lead to impairment of innate immune responses in humans exposed to xenoestrogens. [ABSTRACT FROM AUTHOR]

The multifactorial etiology of autoimmune diseases has been studied at large. Genetic risk factors and environmental agents play an integral role in the pathogenesis of autoimmune processes. In recent decades, Bisphenol A (BPA), an exogenous compound found in polycarbonate plastic, has gained attention for its harmful multifocal effects on a diverse subset of systemic pathways, potentially contributing to disease onset and exacerbation. BPA is a xenoestrogen used globally in the manufacture of daily use products including plastic storage containers, water and infant bottles, and food and drink packaging. BPA exhibits immune stimulatory activity bringing into question the association between its greater global presence and the increased prevalence of autoimmune diseases. The purpose of this multi-study analysis is to assess recent research investigating the underlying role of BPA in autoreactive mechanisms. Although research at present does not directly link BPA exposure to the development of autoimmune diseases, a large body of evidence supports the pro-inflammatory effects of BPA on the immune system. Further studies are required to elucidate the role of BPA in autoimmune pathogenesis, however caution should be taken in the use of BPA containing products by those affected or genetically susceptible to developing autoimmune diseases. [ABSTRACT FROM AUTHOR]

The research indicates that pollution control in developing countries has a limited success. The steroids role in carcinogenesis has become the main anxiety in environmental protection, biomonitoring and the clinical research, environmental health research has been highly focused on the estrogen receptor level and aromatase polymorphisms disturbances. Xenoestrogens and estrogen in the context of environmental exposure play very important role in carcinogenesis by binding to estrogen receptors, whose distribution is described through age and gender. This review provides detailed information about the types of cancer which is etiologically attributed to environmental exposure to xenoestrogens. The types of cancer that have been examined in the literature reviewed on this research is found to be linked with the environmental exposure causing health issues in reproductive system, lung, breast, kidney, pancreas and brain. The result of the data mining on this research problem described strong correlation between the environmental exposures to xenoestrogens with increased intensity of gender related cancer risks. The current study indicates that there was a need to further evaluate agents to this point that were defined as endocrine disruptors and considered as major molecules in carcinogenesis. The revision may be used to further elaborate and discuss the research of cancer aetiology by making further improvements to their related legislation. The research investigates the causes of cancers associated with environmental exposure to xenoestrogens. [ABSTRACT FROM AUTHOR]

Background: The neurochemistry of hepatic nerve fibres was investigated in large animal models after dietary exposure to the endocrine disrupting compound known as bisphenol A (BPA).Materials and Methods: Antibodies against neuronal peptides were used to study changes in hepatic nerve fibres after exposure to BPA at varying concentrations using standard immunofluorescence techniques. The neuropeptides investigated were substance P (SP), galanin (GAL), pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene regulated peptide (CGRP) and cocaine and amphetamine regulated transcript (CART). Immunoreactive nerve fibres were counted in multiple sections of the liver and among multiple animals at varying exposure levels. The data was pooled and presented as mean ± standard error of the mean.Results: It was found that all of the nerve fibres investigated showed upregulation of these neural markers after BPA exposure, even at exposure levels currently considered to be safe. These results show very dramatic increases in nerve fibres containing the above-mentioned neuropeptides and the altered neurochemical levels may be causing a range of pathophysiological states if the trend of over-expression is extrapolated to developing humans.Conclusions: This may have serious implications for children and young adults who are exposed to this very common plastic polymer, if the same trends are occurring in humans. [ABSTRACT FROM AUTHOR]

Benzophenone (BP)-1, BP-2, BP-3, octylmethoxycinnamate (OMC), 4-methylbenzilidenecamphor and homosalate are added to personal care products to absorb ultraviolet light. Their presence in human milk and their oestrogenic activity suggests a potential to influence breast cancer development. As metastatic tumour spread is the main cause of breast cancer mortality, we have investigated the effects of these compounds on migration and invasion of human breast cancer cell lines. Increased motility of oestrogen-responsive MCF-7 human breast cancer cells was observed after long-term exposure (>20 weeks) to each of the six compounds at ≥10−7 m concentrations using three independent assay systems (scratch assay, live cell imaging, xCELLigence technology) and increased invasive activity was observed through matrigel using the xCELLigence system. Increased motility of oestrogen-unresponsive MDA-MB-231 human breast cancer cells was observed after 15 weeks of exposure to each of the six compounds by live cell imaging and xCELLigence technology, implying the increased migratory activity was not confined to oestrogen-responsive cells. Molecular mechanisms varied between compounds and cell lines. Using MCF-7 cells, reduction in E-cadherin was observed following 24 weeks' exposure to 10−5 m BP-1 and 10−5 m homosalate, and reduction in β-catenin was noted following 24 weeks' exposure to 10−5 m OMC. Using MDA-MB-231 cells, increased levels of matrix metalloproteinase 2 were observed after 15 weeks exposure to 10−7 m OMC and 10−7 m 4-methylbenzilidenecamphor. Although molecular mechanisms differ, these results demonstrate that exposure to any of these six compounds can increase migration and invasion of human breast cancer cells. [ABSTRACT FROM AUTHOR]

Copyright of Biologija is the property of Lithuanian Academy of Sciences Publishers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ABSTRACT Several estuaries along the Pacific Ocean coast of North America were identified recently as having elevated 4-nonylphenol (4-NP) in sediments and biota, raising concerns about reproductive impacts for wildlife given 4-NP's established estrogenic activity as an endocrine-disrupting compound. Here we characterize 4-NP mediated induction and recovery of estrogen-sensitive gene transcripts in the arrow goby ( Clevelandia ios), an intertidal fish abundant in estuarine mud flats on the west coast of North America. Male gobies were exposed to waterborne 4-NP at 10 μg/L or 100 μg/L for 20 days followed by a 20 day depuration period. Additional males were treated with 17β-estradiol (E2; 50 ng/L). 4-NP at 100 μg/L elevated hepatic mRNAs encoding vitellogenins A ( vtgA) and C ( vtgC) and choriogenin L ( chgL) within 72 h, and choriogenin H minor ( chgHm) within 12 days. Hepatic mRNAs encoding estrogen receptor alpha ( esr1) were also elevated after 12 days of 4-NP exposure, but returned to pre-exposure levels at 20 days even under continuing 4-NP treatment. 4-NP did not alter mRNA levels of estrogen receptor gamma ( esr2a) in the liver, or of esr1, esr2a, and cytochrome P450 aromatase B ( cyp19a1b) in the brain. The temporal pattern of initial induction for hepatic vtgA, vtgC, and chgL transcripts by 4-NP mirrored the pattern by E2, while chgHm and esr1 mRNA induction by 4-NP lagged 2-11 days behind the responses of these transcripts to E2. These findings establish 4-NP concentration- and time-dependent induction patterns of choriogenin and vitellogenin transcription following exposure to environmentally relevant 4-NP concentrations, while concurrently demonstrating tissue-specific induction patterns for esr1 by estrogenic compounds. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1513-1529, 2017. [ABSTRACT FROM AUTHOR]

Mycotoxins are toxic secondary metabolites formed by various fungal species that are found as natural contaminants in food. This very heterogeneous group of compounds triggers multiple toxic mechanisms, including endocrine disruptive potential. Current risk assessment of mycotoxins, as for most chemical substances, is based on the effects of single compounds. However, concern on a potential enhancement of risks by interactions of single substances in naturally occurring mixtures has greatly increased recently. In this study, the combinatory effects of three mycoestrogens were investigated in detail. This includes the endocrine disruptors zearalenone (ZEN) and α-zearalenol (α-ZEL) produced by Fusarium fungi and alternariol (AOH), a cytotoxic and estrogenic mycotoxin formed by Alternaria species. For evaluation of effects, estrogen-dependent activation of alkaline phosphatase (AlP) and cell proliferation were tested in the adenocarcinoma cell line Ishikawa. The estrogenic potential varied among the single substances. Half maximum effect concentrations (EC50) for AlP activation were evaluated for α-ZEL, ZEN and AOH as 37 pM, 562 pM and 995 nM, respectively. All three mycotoxins were found to act as partial agonists. The majority of binary combinations, even at very low concentrations in the case of α-ZEL, showed strong synergism in the AlP assay. These potentiating phenomena of mycotoxin mixtures highlight the urgent need to incorporate combinatory effects into future risk assessment, especially when endocrine disruptors are involved. To the best of our knowledge, this study presents the first investigation on synergistic effects of mycoestrogens. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate protective effects of quercetin against bisphenol A (BPA) induced testicular toxicity in male Sprague Dawley rats. Twenty adult male rats were divided into four groups. The first group served as the control and was provided with normal saline. The second group of rats was treated with 50 mg/kg of BPA dissolved in alcoholic saline. The third group received oral gavage of 50 mg/kg quercetin while the fourth group was treated with quercetin (50 mg/kg) along with BPA (50 mg/kg). All of the treatments were carried out for 52 days. Testicular tissues and epididymis were used for histology while blood plasma was used for hormonal and biochemical analysis. BPA administration resulted in a significant reduction in seminiferous tubule diameter and epithelial height with impaired spermatogenesis. Quercetin treatment resulted in restoration of spermatogenesis and reversal of histological damage. In addition, BPA treatment significantly reduced (p < 0.05) plasma testosterone level (ng/ml) while estrogen was not affected. Similarly, BPA caused a significant alteration in the lipid profile. Interestingly, quercetin treatment led to a marked increase in plasma testosterone, decrease in estrogen concentration, as well as a normalized lipid profile. In conclusion, results indicated that BPA administration induces toxic effects on testis and epididymis, impairs spermatogenesis, with an imbalance in hormonal levels and lipid profile while quercetin amended these toxic effects by restoring normal spermatogenesis, testicular tissue damage, and hormonal levels. This suggests that quercetin may be a potential therapeutic against BPA induced testicular toxicity. [ABSTRACT FROM AUTHOR]

The prevalence of obesity, metabolic syndrome and type 2 diabetes has dramatically increased worldwide over the last few decades. Although genetic predisposition and lifestyle factors like decreased physical activity and energy-dense diet are well-known factors in the pathophysiology of these conditions, accumulating evidence suggests that the increase in endocrine disrupting chemicals (EDCs) in the environment also explains a substantial part of the incidence of these metabolic diseases. Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide. Most people are exposed to it daily by consuming food and beverages into which BPA has leached from polycarbonate containers, including reusable bottles and baby bottles. Although initially considered to be a weak environmental estrogen, BPA may be similar in potency to 17β-estradiol in stimulating cellular responses, especially at low but environmentally relevant doses (nM), as more recent studies have demonstrated. In this review, we summarize both epidemiological evidence and in vivo experimental data that point to an association between BPA exposure and the induction of insulin resistance and/or disruption of pancreatic beta cell function and/or obesity. We then discuss the in vitro data and explain the potential mechanisms involved in the metabolic disorders observed after BPA exposure. [ABSTRACT FROM AUTHOR]

In this study, photocatalytic and catalytic wet-air oxidation (CWAO) processes were used to examine removal efficiency of bisphenol A from aqueous samples over several titanate nanotube-based catalysts. Unexpected toxicity of bisphenol A (BPA) samples treated by means of the CWAO process to some tested species was determined. In addition, the CWAO effluent was recycled five- or 10-fold in order to increase the number of interactions between the liquid phase and catalyst. Consequently, the inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated higher concentrations of some toxic metals like chromium, nickel, molybdenum, silver, and zinc in the recycled samples in comparison to both the single-pass sample and the photocatalytically treated solution. The highest toxicity of five- and 10-fold recycled solutions in the CWAO process was observed in water fleas, which could be correlated to high concentrations of chromium, nickel, and silver detected in tested samples. The obtained results clearly demonstrated that aqueous samples treated by means of advanced oxidation processes should always be analyzed using (i) chemical analyses to assess removal of BPA and total organic carbon from treated aqueous samples, as well as (ii) a battery of aquatic organisms from different taxonomic groups to determine possible toxicity. [ABSTRACT FROM AUTHOR]

Myelin is the functional implication of oligodendrocytes (OLs), which is involved in insulation of axons and promoting rapid propagation of action potential in the brain. OLs are derived from oligodendrocyte progenitor cells (OPCs), which proliferate, differentiate, and migrate throughout the central nervous system. Defects in myelination process lead to the onset of several neurological and neurodegenerative disorders. Exposure to synthetic xenoestrogen bisphenol-A (BPA) causes cognitive dysfunction, impairs hippocampal neurogenesis, and causes onset of neurodevelopmental disorders. However, the effects of BPA on OPC proliferation, differentiation and myelination, and associated cellular and molecular mechanism(s) in the hippocampus of the rat brain are still largely unknown. We found that BPA significantly decreased bromodeoxyuridine (BrdU)-positive cell proliferation and number and size of oligospheres. We observed reduced co-localization of BrdU with myelination markers CNPase and platelet-derived growth factor receptor-α (PDGFR-α), suggesting impaired proliferation and differentiation of OPCs by BPA in culture. We studied the effects of BPA exposure during prenatal and postnatal periods on cellular and molecular alteration(s) in the myelination process in the hippocampus region of the rat brain at postnatal day 21 and 90. BPA exposure both in vitro and in vivo altered proliferation and differentiation potential of OPCs and decreased the expression of genes and levels of proteins that are involved in myelination. Ultrastructural electron microscopy analysis revealed that BPA exposure caused decompaction of myelinated axons and altered g-ratio at both the developmental periods as compared to control. These results suggest that BPA exposure both during prenatal and postnatal periods alters myelination in the hippocampus of the rat brain leading to cognitive deficits. [ABSTRACT FROM AUTHOR]

In the present study, the effects of xenoestrogen 4-nonylphenol (4-NP) and 17β-estradiol (E2) on the synthesis of vitellogenin (VTG) in immature male yellowfin seabream (Acanthoparus latus) were assessed to determine the potential use of this species as a biological model for studying endocrine disrupters in the Musa estuary in southern seawaters of Iran. A total number of 104 fish were injected by 10, 50, 100, 150 and 200 µg g−1 week−1 of 4-NP and 2 µg g−1 week−1 of E2, and their blood plasma was obtained for biochemical analysis on days 0, 7 and 14. The hepatosomatic index (HSI) of each fish was also recorded at each sampling time. The results showed that 4-NP significantly induced VTG synthesis in A. latus, which was detected by gel electrophoresis as two major protein bands (∼210 and 191 KDa). The induction of VTG was also determined indirectly by measuring the alkali-labile phosphate, total plasma calcium and protein. All of these VTG indicators significantly increased in the plasma of 4-NP- and E2-treated fish. Meanwhile, a significant dose-dependent increase was observed in HSI, indicating the activation of hepatic VTG production in 4-NP- and E2-injected fish. Furthermore, the plasma alanine aminotransferase and aspartate aminotransferase concentrations significantly increased in 4-NP-treated fish, presumably reflecting a situation of hepatic tissue damage due to 4-NP toxicity. Based on the results, it is suggested that A. latus could be used successfully as a model species for future studies of endocrine disrupting contaminants in the Musa estuary. [ABSTRACT FROM PUBLISHER]

Perinatal exposure to endocrine disrupting chemicals (EDCs) can induce promiscuous neurobehavioral disturbances. Bisphenol A and phthalates are two widely prevalent and persistent EDCs reported to lead to such effects. Parental and social behaviors are especially vulnerable to endocrine disruption, as these traits are programmed by the organizational-activational effects of testosterone and estrogen. Exposure to BPA and other EDCs disrupts normal maternal care provided by rodents and non-human primates, such as nursing, time she spends hunched over and in the nest, and grooming her pups. Paternal care may also be affected by BPA. No long-term study has linked perinatal exposure to BPA or other EDC and later parental behavioral deficits in humans. The fact that the same brain regions and neural hormone substrates govern parental behaviors in animal models and humans suggests that this suite of behaviors may also be vulnerable in the latter. Social behaviors, such as communication, mate choice, pair bonding, social inquisitiveness and recognition, play behavior, social grooming, copulation, and aggression, are compromised in animal models exposed to BPA, phthalates, and other EDCs. Early contact to these chemicals is also correlated with maladaptive social behaviors in children. These behavioral disturbances may originate by altering the fetal or adult gonadal production of testosterone or estrogen, expression of ESR1, ESR2, and AR in the brain regions governing these behaviors, neuropeptide/protein hormone (oxytocin, vasopressin, and prolactin) and their cognate neural receptors, and/or through epimutations. Robust evidence exists for all of these EDC-induced changes. Concern also exists for transgenerational persistence of such neurobehavioral disruptions. In sum, evidence for social and parental deficits induced by BPA, phthalates, and related chemicals is strongly mounting, and such effects may ultimately compromise the overall social fitness of populations to come. [ABSTRACT FROM AUTHOR]

Molecularly imprinted microspheres containing binding sites for the extraction of 4-cumylphenol have been prepared for the first time. The imprinted microspheres were synthesized by a precipitation method using 4-cumylphenol as a template molecule, methacrylic acid as a functional monomer and divinylbenzene-80 as a cross-linker for polymer network formation. The formation and the morphology of molecularly imprinted microspheres were well characterized using infrared spectroscopy, thermogravimetric studies, and scanning electron microscopy. The Brunauer-Emmett-Teller analysis revealed the high surface area of the sorbent indicating formation of molecularly imprinted microspheres. The developed microspheres were employed as a sorbent for the solid-phase extraction of 4-cumylphenol and showed fast uptake kinetics. The sorption parameters were optimized to achieve efficient sorption of the template molecule, like pH, quantity of molecularly imprinted microspheres, time required for equilibrium set-up, sorption kinetics, and adsorption isotherm. A standard method was developed to analyze the sorbed sample quantitatively at 279 nm using high-performance liquid chromatography with diode array detection. It was validated by determining target analyte from synthetic samples, bottled water, spiked tap water, and soil samples. The prepared material is a selective and robust sorbent with good reusability. [ABSTRACT FROM AUTHOR]

1. Breast cancer resistance protein (BCRP) is an ABC-transporter at the blood-brain barrier (BBB) facilitating efflux of xenobiotics into blood. Expression and function are regulated via estrogen-receptors (ERs). 2. 17α-Ethinylestradiol (EE2) and bisphenol A (BPA) represent two prominent xenoestrogens. We studied whether EE2 and BPA regulate BCRP function and expression upon a 6 h treatment in an ER-dependent manner in a rat BBB- ex-vivo-model. 3. Isolated brain capillaries were incubated with EE2 or BPA. BCRP function and expression were analyzed by confocal microscopy and Western-Blot. ERα-antagonist MPP and ER-antagonist ICI182.780 were used to study involvement of ERs. 4. EE2 and BPA down-regulated BCRP transport function and expression. EE2 effects occurred at pharmacologically relevant doses, BPA exhibited only weak influences. Down-regulation by EE2 was reversed by ICI but not MPP. BPA effects were not reversed by either antagonist. 5. EE2 is a potent regulator of BCRP expression and function acting by ERβ-stimulation. Oral contraception could alter uptake of pharmaceuticals to the brain and might thus be considered as an origin of central nervous system (CNS) side-effects. EE2 could alsopresent a novel co-treatment to improve CNS-pharmacotherapy. BPA is a weak modulator of BCRP expression. Its effects appear not to be caused by ERs. [ABSTRACT FROM AUTHOR]

ABSTRACT Alkyl esters of p-hydroxybenzoic acid (parabens) are widely used as preservatives in personal care products, foods and pharmaceuticals. Their oestrogenic activity, their measurement in human breast tissue and their ability to drive proliferation of oestrogen-responsive human breast cancer cells has opened a debate on their potential to influence breast cancer development. As proliferation is not the only hallmark of cancer cells, we have investigated the effects of exposure to parabens at concentrations of maximal proliferative response on migratory and invasive properties using three oestrogen-responsive human breast cancer cell lines (MCF-7, T-47-D, ZR-75-1). Cells were maintained short-term (1 week) or long-term (20 ± 2 weeks) in phenol-red-free medium containing 5% charcoal-stripped serum with no addition, 10-8 M 17β-oestradiol, 1-5 × 10-4 M methylparaben, 10-5 M n-propylparaben or 10-5 M n-butylparaben. Long-term exposure (20 ± 2 weeks) of MCF-7 cells to methylparaben, n-propylparaben or n-butylparaben increased migration as measured using a scratch assay, time-lapse microscopy and xCELLigence technology: invasive properties were found to increase in matrix degradation assays and migration through matrigel on xCELLigence. Western immunoblotting showed an associated downregulation of E-cadherin and β-catenin in the long-term paraben-exposed cells which could be consistent with a mechanism involving epithelial to mesenchymal transition. Increased migratory activity was demonstrated also in long-term paraben-exposed T-47-D and ZR-75-1 cells using a scratch assay and time-lapse microscopy. This is the first report that in vitro, parabens can influence not only proliferation but also migratory and invasive properties of human breast cancer cells. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Being lipophilic xenobiotic chemicals, phthalates from the surrounding environments can easily be absorbed into the biological system, thereby causing various health problems including cancer and endocrine disruption in test animals and also in humans. In the presentin silicostudy employing Glide, Schrödinger Suite 2012, we analysed in detail the binding affinities of 12 commonly used diphthalates and their metabolites (corresponding mono ester and phthalic acid) onto the ligand-binding domain (LBD) of the human estrogen receptor α (hERα), human estrogen receptor β (hERβ) and human estrogen related receptor γ (hERRγ). Natural ligand 17β estradiol (E2), known xenoestrogen bisphenol A, the phytoestrogen genistein, the agonists/antagonists 4-hydroxy tamoxifen and raloxifene were also docked onto these receptors as positive controls for comparing the binding efficiencies with that of phthalates and their metabolites. Results revealed that E2 had less binding affinity to the receptors in comparison to certain phthalates, i.e. maximum binding scores (G score, kcal/mol) were diisononyl phthalate ( − 9.44) to hERα, monophenyl phthalate ( − 8.66) to hERβ and di(2-ethylhexyl)phthalate ( − 9.38) to hERRγ. The most concerned monophthalates established additional H bonds with certain surrounding crucial amino acid residues in the LBD, and thus showed more affinity to all the receptors than even the natural ligand and other well-characterised xenoestrogens as demonstrated in this study. Briefly, this study gives an insight into the virtual binding behaviours of commonly used phthalates and their metabolites onto hERs and hERRγ, which would accelerate furtherin vitromechanistic, preclinical and clinical studies on realin vitroorin vivoplatforms. [ABSTRACT FROM PUBLISHER]

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Bisphenol A (BPA) is a widespread environmental contaminant detected in urine of 93 % of investigated US population. Recent epidemiological studies found correlation between BPA exposure and diseases including cardiovascular and neuronal disorders. BPA targets include hormone receptors and voltage-dependent ion channels. T-type calcium channels are important regulatory elements in both cardiovascular and neuronal system. Therefore, we investigated effects of BPA on T-type calcium channels. Calcium current flowing through recombinant T-type calcium channels expressed in HEK 293 cells was measured using whole-cell patch clamp. BPA inhibited the current through individual T-type calcium channel subtypes in a concentration-dependent manner with two distinguishable components in these concentration-dependencies. Nanomolar concentrations of BPA inhibited calcium current through T-type calcium channels in the order of efficiency Ca3.2 ≥ Ca3.1 > Ca3.3 without affecting voltage dependence and kinetics of channel gating. Micromolar concentrations of BPA accelerated kinetics of current decay, shifted voltage dependence of steady-state inactivation towards more negative values and inhibited current amplitudes. We suggest that BPA acts as a modifier of channel gating and directly plugs conductive channel pore at high concentration. Concentration range in which inhibition was observed corresponds to concentrations detected in human fluids and therefore may be relevant for evaluation of health effects of BPA. [ABSTRACT FROM AUTHOR]

A method for simultaneous analysis of bisphenol A (BPA) and 17α-ethinylestradiol (EE2) in water supply was developed using solid-phase extraction and high-performance liquid chromatography with fluorescence detection. The linearity was evaluated between 2.5 and 200 μg L (r> for the analytes. The limits of quantification were 1.5 and 2.1 ng L for BPA and EE2, respectively. The extraction was made with C18 cartridges, and recoveries obtained varied between 70 and 102 % for the strengthening of 5 μg L. After the validation, the method was applied in the determination of pollutants in surface water and water supply of Sao Luis, Brazil, where BPA was found in two of the eight samples analyzed, with concentrations of 1.11 and 3.61 μg L. [ABSTRACT FROM AUTHOR]

Vitellogenin (Vtg) is the major egg-yolk precursor protein in oviparous organisms normally synthesised only in mature females. In males and juveniles, the vtg gene, although present, is silent, but its hepatic expression may be activated by xenoestrogens. Surprisingly, its induction and potential consequences in non-hepatic tissues remain unexplored. Here we test the hepatic and testicular response of vtg expression in adult male rainbowfish Melanotaenia fluviatilis exposed to either 1, 3, 5 μg/L 17β-estradiol or 100, 500 μg/L 4- n-nonylphenol for 24-96 h. Significant increase in the expression level of vtg mRNA in the liver and testes of exposed males was observed. The early (24 h), sensitive and reliable detection of the vtg induction using qPCR demonstrates the assay's robustness to monitor xenobiotic exposure particularly in smaller fish like rainbowfish, an emerging indicator species. Whilst, the ectopic induction of vtg mRNA in testes suggests a more complex Vtg pathway. [ABSTRACT FROM AUTHOR]

Biosolids applied to agricultural fields, parks, and other areas represent significant sources of estrogen-like endocrine disrupting compound (EEDC) inputs to soil. It is important to determine the bioavailability of EEDCs in soil to inform risk assessment concerning their environmental presence; Eisenia fetida (earthworms) are typically used in traditional in vivo bioavailability experiments. The development of an in vitro bioavailability method will decrease time, expense, and use of solvents in future analyses. A thin-film solid-phase microextraction (TF-SPME) method for determining the bioavailability of several EEDCs detected in biosolids was developed and optimized. It was found that the TF-SPME method could be used to calculate equilibrium porewater concentrations of diethylhexyl phthalate, bisphenol A, benzophenone, and triclosan at environmentally relevant concentrations in artificial soil within 88 min. The potential and limitations of using TF-SPME-generated porewater concentrations to predict E. fetida tissue concentrations are discussed. Environ Toxicol Chem 2013;32:1962-1968. © 2013 SETAC [ABSTRACT FROM AUTHOR]

We are now witnessing a resurgence of theories of development and carcinogenesis in which the environment is again being accepted as a major player in phenotype determination. Perturbations in the fetal environment predispose an individual to disease that only becomes apparent in adulthood. For example, gestational exposure to diethylstilbestrol resulted in clear cell carcinoma of the vagina and breast cancer. In this review the effects of the endocrine disruptor bisphenol-A (BPA) on mammary development and tumorigenesis in rodents is used as a paradigmatic example of how altered prenatal mammary development may lead to breast cancer in humans who are also widely exposed to it through plastic goods, food and drink packaging, and thermal paper receipts. Changes in the stroma and its extracellular matrix led to altered ductal morphogenesis. Additionally, gestational and lactational exposure to BPA increased the sensitivity of rats and mice to mammotropic hormones during puberty and beyond, thus suggesting a plausible explanation for the increased incidence of breast cancer. [ABSTRACT FROM AUTHOR]

Human exposure to bisphenol A (BPA), a synthetic estrogen found in numerous consumer products, is widespread. However, scientific knowledge about the sources and routes of exposure remains incomplete. Although human biomonitoring studies report small amounts of bioactive BPA in the blood of most subjects, toxicokinetic models suggest that circulating levels should be undetectable. The conflict between reported data and toxicokinetic models has spurred considerable debate, with some suggesting that data from analyses of human blood should be dismissed in their entirety. This review addresses the assumptions used by previous risk assessment panels regarding the sources and routes of exposure to BPA (specifically, that BPA exposures occur solely via a few dietary sources) and how these assumptions have affected the interpretation of BPA studies. Given new experimental evidence that route of exposure influences BPA pharmacokinetics, we consider the implications of basing regulatory decisions on limited data that have provided incomplete information about the products that contain this chemical and how it enters the body. We also address evidence that challenges the assumption that humans metabolize BPA rapidly enough to result in undetectable levels in blood and therefore determine that there is a possibility of harm from current exposure levels. Our conclusions are consistent with the large number of hazards and adverse effects identified in laboratory animals exposed to low doses of BPA. [ABSTRACT FROM AUTHOR]

The aim of the study was to explore whether G-Protein-Coupled Receptor 30 (GPR30) was expressed in rat testicular Sertoli cells and to assess the impact of monobutyl phthalate (MBP) on the expression of GPR30 in Sertoli cells. By using RT-PCR, Western-Blot and immunofluorescent microscopy, the expression of GPR30 in rat Sertoli cells was found at both gene and protein level. Cultures of Sertoli cells were exposed to MBP (10-1000 µM) or a vehicle. The results indicated that the expression of GPR30 increased at gene and protein levels in Sertoli cells following administration of MBP even at a relatively low concentration. We suggest that changes of GPR30 expression may play an important role in the effects of the xenoestrogen MBP on Sertoli cell function. [ABSTRACT FROM AUTHOR]

Environmental change can increase the likelihood of interspecific hybridization by altering properties of mate recognition and discrimination between sympatric congeners. We examined how exposure to an environmentally widespread endocrine- disrupting chemical (EDC), bisphenol A (BPA), affected visual communication signals and behavioral isolation between an introduced freshwater fish and a native congener (genus: Cyprinella). Exposure to BPA induced changes in the expression of male secondary traits as well as male and female mate choice, leading to an overall reduction in prezygotic isolation between congeners. Changes in female mate discrimination were not tightly linked to changes in male phenotypic traits, suggesting that EDC exposure may alter female choice thresholds independently of the effects of exposure on males. These findings indicate that environmental exposure to EDCs can lead to population declines via the erosion of species boundaries and by promoting the establishment and spread of non-native species via hybridization. [ABSTRACT FROM AUTHOR]

Objectives We investigated the association between occupational exposure to endocrine-disrupting chemicals (EDC) and the risk of uveal melanoma using international data of a case-control study from nine European countries. Methods After exclusion of proxy interviews, 280 cases and 3084 control subjects were included in the final analysis. Information on possible exposure to EDC was derived from 27 job-specific questionnaires (JSQ), which solicited detailed questions on occupational tasks. Relative risk estimates were based on the JSQ and potential exposure to a group of endocrine-disrupting agents. We constructed several exposure scores, taking into account intensity of exposure, use of personal protective equipment, and exposure duration. We calculated unconditional logistic regression analyses, adjusting for country, age, sex, eye color and a history of ocular damage due to intense ultraviolet (UV) exposure. Results The overall exposure prevalence to EDC was low reaching a maximum of 11% for heavy metals with endocrine-disrupting properties. Although working in some industries was associated with increased melanoma risk [such as dry cleaning: odds ratio (OR) 6.15,95% confidence interval (95% CI) 2.0-18.96 and working in the glass manufacturing industry: OR 3.49,95% CI 1.10-11.10], agent-specific risks were not elevated. The strongest possible risk increase was observed for organic solvents with endocrine-disrupting properties (OR 1.31, 95% CI 0.78-2.21). Calculation of exposure scores did not indicate consistently elevated results with higher score values. Sensitivity analyses did not alter these results. Conclusion Occupational exposure to EDC was not associated with an increased risk for uveal melanoma. [ABSTRACT FROM AUTHOR]

The advent of modern medicine has allowed for significant advances within the fields of emergency care, surgery, and infectious disease control. Health threats that were historically responsible for immeasurable tolls on human life are now all but eradicated with incertain populations, specifically those that enjoy higher degrees of socio-economic status and access to healthcare. However, modernization and its resulting lifestyle trends have ushered in anewera of chronicillness; one in which anunprecedented number of peo-pleare estimated to contract cancer and other inflammatory diseases. Here, we explore the idea that homeostasis has been redefined within just a few generations, and that diseases such as colorectal cancer are the result of fluctuatingphy siological and molecu-larimbalances.Phytochemical-deprived, pro-inflammatory dietscombined with low-dose exposures to environmental toxins, including bisphenol-A (BPA) and other endocrinedis-ruptors, are now linked to increasing incidences of cancer in westernized societies and developing countries. There is recent evidence that disease determinants are likely set in utero and further perpetuated in to adulthood dependent upon the innate and environmentally acquired phenotype unique to each individual. In order to address a disease as multi-factorial, case-specific, and remarkably adaptive as cancer, research must focus on its root causes in order to elucidate the molecular mechanisms by which they can be prevented or counteracted via plant-derived compounds such as epigallocatechin-3-gallate (EGCG) and resveratrol. The significant role of epigenetics in the regulation of these complex processes is emphasized here to form a comprehensive view of the dynamic interactions that influence modern-day carcinogenesis, and how sensibly restoring homeostatic balance may be the key to the cancer riddle. [ABSTRACT FROM AUTHOR]

The declining level of androgen during aging, associated with an inclining level of estrogen, has been hypothesized to be important in the development of benign prostatic hyperplasia (BPH). Within physiologic range, increasing estrogen levels can stimulate prostate to develop and permanently increase prostate size. As an estrogenic endocrine disruptor, bisphenol A (BPA) might be stimulatory to prostate development. We further hypothesized that low dose BPA could induce hyperplasia prostate to proliferate and aggravate the symptom of BPH in male SD rats. BPH was induced by testosterone and then treated with BPA (10, 30, or 90 μg/kg, i.g., daily), 17β-estradiol (E2; 50.0 μg/kg, s.c., daily), or vehicle for 4 weeks. We found that weight and volume in rats treated with low dose BPA (10 μg/kg) was higher than that of model control, and BPA significantly increased the relative weight of prostate (p < 0.01). For prostate lobes, BPA 10 μg/kg/day significantly increased relative weight of ventral prostate (VP), weight and relative weight of dorsolateral prostate (DLP) (p < 0.05). And histopathology results showed that height of epithelial cell (HEC) of VP and DLP in BPA group were significantly higher than that of model control (p < 0.01). BPA could also decrease testostertone level and increase prostate-specific antigen level. E2 treatment also showed an obvious effect on relative weight of VP and DLP, HEC, and hormone levels. We concluded that environment exposure to low dose of BPA may induce prostate to proliferate and aggravate testosterone-induced benign hyperplasia prostate in rats. [ABSTRACT FROM PUBLISHER]

The estrogenic mycotoxin zearalenone (ZEN) can undergo hepatic reductive metabolism to form the estrogenic α and β isomers of zearalenol. ZEN also undergoes cytochrome P450 monooxygenase (P450)-mediated oxidative metabolism to form monohydroxylated products, but until now nothing is known about the estrogenic potency of these metabolites. This study aimed at investigating the metabolism of ZEN by different P450 isoforms and to determine the estrogen receptor α (ERα) affinities of the in vitro P450-generated ZEN metabolites in an online high-resolution screening (HRS) setup. Human liver microsomes (HLM), recombinant P450s, and mutants of the bacterial P450 BM3 were used to investigate the oxidative metabolism of ZEN. It was shown that mutants of the bacterial P450 BM3 could be used to produce the human relevant 13- and 15-OH-ZEN catechol metabolites at such levels that their ERα affinity could be determined in an HRS setup, which was not possible with HLM. It was demonstrated that P450-mediated hydroxylation at the 13 and 15 positions of ZEN resulted in a loss of ERα affinity. The approach presented here can be used for the elucidation of the metabolism of other endocrine disrupting compounds and xenobiotics to get clear pictures of the total effects of these compounds and their metabolites. [ABSTRACT FROM AUTHOR]

Lung cancer is a dominant cause of cancer mortality. The etiology of lung cancer is mainly related to cigarette smoking, airborne genotoxic carcinogens, and arsenic, but its sex-specific incidence suggests that other mechanisms, such as hormones, may also be involved in the process of carcinogenesis. A number of agents commonly present in the living environment can have dual biological effects: not only are they genotoxic / carcinogenic, but they are also hormonally active as xenoestrogens. This dualism may explain sex-specific differences reported in both types and incidence of lung cancer. In a novel approach to investigate the complexity of lung cancer, etiology, including systems biology, will be used as a tool for a simultaneous interpretation of measurable environmental and biological parameters. Using this approach, the etiology of human lung cancer can be more thoroughly investigated using the available data from oncology and environmental health. The information gained could be applied in the introduction of preventive measures, in personalized medicine, and in more relevant legislation, which should be adjusted to reflect the current knowledge on the complex environmental interactions underlying this life-threatening disease. [ABSTRACT FROM PUBLISHER]

Xenoestrogens can affect the healthy functioning of a variety of tissues by acting as potent estrogens via nongenomic signaling pathways or by interfering with those actions of multiple physiological estrogens. Collectively, our and other studies have compared a wide range of estrogenic compounds, including some closely structurally related subgroups. The estrogens that have been studied include environmental contaminants of different subclasses, dietary estrogens, and several prominent physiological metabolites. By comparing the nongenomic signaling and functional responses to these compounds, we have begun to address the structural requirements for their actions through membrane estrogen receptors in the pituitary, in comparison to other tissues, and to gain insights into their typical non-monotonic dose-response behavior. Their multiple inputs into cellular signaling begin processes that eventually integrate at the level of mitogen-activated protein kinase activities to coordinately regulate broad cellular destinies, such as proliferation, apoptosis, or differentiation. [ABSTRACT FROM PUBLISHER]

Oestrogens contribute to the female preponderance of autoimmune diseases such as systemic lupus erythematosus (SLE). Environmental xenoestrogens superimposed upon endogenous pituitarygonadal axis may affect the development of autoimmunity. This study examined the effects of chronic exposure to xenoestrogens - o,p'-dichlorodiphenyltrichloroethane (DDT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on disease activity in the New Zealand Black/New Zealand White F1 hybrid (B/W) mousemodel of SLE. Intact female mice had repeatedly received injections of DDT, TCDD or control vehicle since 6 weeks of age. Weight change, albuminuria, mortality, relevant immunological and histological parameters were assessed. DDT exposure markedly increased the incidence of albuminuria and reduced uterine weight but had no measured effects on immunity or mortality in this study. TCDD-exposed mice had significantly lower incidence of albuminuria, serum anti-DNA antibody and total IgG levels, and mortality compared to controls. Also, TCDD group had significantly lower thymic and splenic weights, decreased percentages of CD4+CD8+ thymocytes and splenic CD4+ T cells, increased percentage of splenic B220+sIgM+ B cells and higher serum interferon gamma concentration. Taken together, DDT exposure appeared to accelerate the development of albuminuria in lupus-prone mice. TCDD was immunosuppressive to murine SLE. Xenoestrogens may have compound- and tissue-specific effects that require further elucidation in future work. [ABSTRACT FROM AUTHOR]