Environmental Endocrine-disrupting Compounds Research Articles

Synthesis of a Cu-Al bimetallic oxide @ PVDF composite membrane for the degradation of bisphenol a via peroxydisulfate activation: Performance and mechanism

The presence of environmental endocrine-disrupting compounds, such as bisphenol A (BPA), in aquatic environments poses a significant risk to both ecological integrity and human health. Although CuO has been reported as a catalyst for activating peroxydisulfate (PDS) to degrade BPA, it exhibits certain limitations, including low catalytic efficiency, aggregation, and challenges in terms of separation and reusability. In this study, we developed a composite poly (vinylidene fluoride) (PVDF)-based membrane incorporating Cu-Al bimetallic oxide (Cu-Al) to address these issues. Results revealed that when employing the 7 wt% Cu-Al @ PVDF composite membrane to activate 1 mM PDS, approximately 95.3 % of BPA was degraded within 60 min in static experiments. Furthermore, this composite membrane exhibited remarkable efficacy across a broad pH range (3–11) and demonstrated excellent resistance against diverse anionic species. The removal process is proposed to be dominated by electron transfer between the composite membrane, PDS, and BPA via a two-step mechanism: Firstly, electron-rich Cu sites and oxygen vacancies were formed in the composite membrane, facilitating PDS adsorption and electron transfer from Cu sites to PDS to form a ligand complex; subsequently, BPA was adsorbed by the membrane and acted as an electron donor to be oxidized by the ligand complex. As a result, this system showed remarkable selectivity for degrading electron-rich organic compounds with ionization potentials below 9.0 eV. Overall, this work successfully fabricated a catalytic membrane exhibiting efficient PDS activation capability along with selective oxidation performance and facile reusability, making it highly promising for wastewater treatment.

Binding interactions of EDCs to human estrogen‐related receptor gamma deciphered by multiple molecular dynamics and energy calculations

AbstractDichloro‐diphenyl‐trichloroethane (DDT) analogs, classified as environmental endocrine disrupting compounds (EDCs), have been extensively employed as potent insecticides that can cause endocrine system disruption. However, the precise dynamic structural characteristics and interactions between human estrogen‐related receptor gamma (hERRγ) and DDT analogs are not yet fully understood. In this study, we comprehensively investigate the impact of these EDCs (DDT, dichloro‐diphenyl‐dichloroethane (DDD), 2,2‐bis(4‐chlorophenyl)ethanol (DDOH), O,P′‐DDT (2,4′‐DDT), 4,4′‐dichlorobenzophenone (DCBP), and 4‐hydrotamoxifen (4‐OHT) on the structural changes of hERRγ and their interaction mechanisms by employing multiple molecular dynamics (MD) simulations coupled with MM‐PBSA and SIE approaches. The consequence manifested that overall structures of these six complexes did not transform markedly, but these compounds can affect the local hERRγ structure, leading to essential changes in interactions with pivotal residues nearby L268, V313, L309, Y326, and F435. And van der Waals interactions are the key to how these EDCs interact with hERRγ. These outcomes contribute to our comprehension the risks of DDT analogues to human health.

Public perception on human exposure risk: A case study on endocrine disrupting compounds in the environment

Humans are exposed to environmental risks owing to the broad usage of endocrine disrupting compounds (EDCs). However, the subjective evaluation of risk levels and characteristics, as well as the variation in risk processing, have not been thoroughly examined. The objective was to understand the public's perception of the risk associated with human exposure to environmental EDCs and identify any variations in risk perception. In this pioneering study conducted within the distinctive social and cultural context of Malaysia, a developing nation, a quantitative analysis approach was employed to assess the subjective evaluation of risk levels and characteristics among the public while developing a risk perception model. Data gathered from surveys and questionnaires were analyzed to gather information on the public's perception of environmental and health issues pertaining to pesticides, hormones, plastics, medicines, and cosmetics. The analysis revealed that the majority of the public assessed the level of human exposure to environmental risks based on experiential processing, which was influenced by cognitive and affective variables. Interestingly, a higher proportion of individuals in the community had a low risk perception of environmental EDCs, surpassing the overall risk perception by 19.3%. Furthermore, the public showed significant awareness of environmental and health issues related to pesticides, hormones, and plastics but had a lesser inclination to acknowledge the vulnerability of humans to risks associated with medicines and cosmetics. These findings suggest that the public is likely to be exposed to environmental EDCs based on their current perceived risks, and that sociopsychological factors play a significant role in shaping perceptions and judgments. This understanding can inform the development of targeted risk management strategies and interventions to mitigate the potential harm caused by environmental EDCs.

Association of polycyclic aromatic hydrocarbons with osteoarthritis among adults: an analysis of the NHANES 2001-2016.

Polycyclic aromatic hydrocarbons (PAHs) are environmental endocrine-disrupting compounds, which have been widely recognised as a risk factor for human health. However, the relationship between PAHs exposure and the risk of osteoarthritis has rarely been reported. This study aimed to investigate the association between individual and mixed exposure to PAHs and osteoarthritis. In this cross-sectional study, participants aged ≥20 years with data on urinary PAHs and osteoarthritis were extracted from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2016. Logistic regression analysis was utilised to assess the relationship between individual PAHs exposure and osteoarthritis. The quantile-based g computation (qgcomp) analysis and Bayesian kernel machine regression (BKMR) analysis were performed to assess the effect of mixed exposure to PAHs on osteoarthritis, respectively. A total of 10,613 participants were enrolled, 980 (9.23%) of whom had osteoarthritis. Exposure to high levels of 1-hydroxynaphthalene (1-NAP) [odds ratio (OR)=1.06, 95% confidence interval (CI): 1.01-1.10], 3-hydroxyfluorene (3-FLU) (OR=1.09, 95%CI: 1.02-1.17), and 2-hydroxyfluorene (2-FLU) (OR=1.06, 95%CI: 1.01-1.13) were all associated with greater odds of osteoarthritis after adjusting for age, sex, body mass index, drinking alcohol, and hypertension. The qgcomp analysis showed that the joint weighted value of mixed PAHs exposure (OR=1.11, 95%CI: 1.02-1.22; p=0.017) was significantly related to higher odds of osteoarthritis. The BKMR analysis demonstrated that mixed exposure to PAHs was positively correlated with the risk of osteoarthritis. Both individual and mixed exposure to PAHs were positively correlated with the risk of osteoarthritis.

Influence on the adult male Leydig cell biomarker insulin-like peptide 3 of maternal exposure to estrogenic and anti-androgenic endocrine disrupting compound mixtures: A retrospective study.

Insulin-like peptide 3 (INSL3) is a peptide biomarker secreted specifically by the mature Leydig cells of the testes. It is constitutive, has low within-individual variance, and effectively measures the functional capacity of Leydig cells to make testosterone. In young adult men there is a large 10-fold range of serum INSL3 concentration, persisting into old age, and implying that later hypogonadal status might be programmed in early life. To determine whether maternal exposure to environmental endocrine disrupting compounds (EDCs) influences adult serum INSL3 concentration, using a retrospective paradigm, INSL3 was measured in young adult male rats (80-90 days) from the F1 generation of females maternally exposed to varied doses of bisphenol A (BPA), butylparaben, epoxiconazole, and fludioxonil as single compounds, as well as estrogenic and anti-androgenic mixtures of BPA and butylparaben, and di(2-ethylhexyl) phthalate and procymidone respectively. A mixture of BPA and butylparaben significantly reduced circulating INSL3 concentration in adult male progeny. The remaining compounds or mixtures tested, though sufficient to induce other effects in the F1 generation were without significant effect. Maternal exposure to low concentrations of some EDCs may be a contributing factor to the variation in the Leydig cell biomarker INSL3 in young adulthood, though caution is warranted translating results from rats to humans.

Bioinspired synthesis of hematite nanoparticles-reduced graphene oxide composite for application in bisphenol a detection: A new in-sight

Bisphenol A (BPA), one of the well-known environmental endocrine-disrupting compounds, has an effective estrogenic activity that badly impacts the environment and human health. Therefore, an urgent need arises to develop a simple and effective method for BPA detection. Herein, we report novel, disposable and flexible nanoplatforms for electrochemical determination of BPA using carbon cloth electrode supported hematite nanoparticles (α-Fe2O3NPs) on reduced graphene oxide (rGO) composite. The α-Fe2O3NPs@rGO composite was synthesized through a green route using leaves extract of Cinnamomum tamala that acted as a reducing and stabilizing agent for α-Fe2O3NPs followed by the addition of graphene oxide to convert it into rGO. The nanoplatform was fabricated using the electrophoretic deposition technique on carbon cloth (CC) substrate, i.e., (α-Fe2O3NPs@rGO/CC). The analytical performance of α-Fe2O3NPs@rGO/CC nanoplatform is ascribed to the synergistic effect of α-Fe2O3NPs and rGO that resulted in a larger active surface to volume ratio, superior conductivity, and enhanced electrochemical behavior. The fabricated α-Fe2O3NPs@rGO/CC nanoplatform exhibited a broad linear range from 1.9 × 10−10 to 1.00 μM having a higher sensitivity of 33.04 μA (log μM)−1 cm−2 and a low limit of detection of 0.23 μM. It also displayed excellent selectivity, repeatability, reproducibility, and stability with satisfying results. Moreover, the electrochemical nanoplatform helped analyze the real samples to detect BPA with acceptable results. Hence, this nanoplatform could be further utilized to detect other estrogenic analytes.

Prenatal exposure to di-n-butyl phthalate induces erectile dysfunction in male adult rats

Di-n-butyl phthalate (DBP) is a widely used plasticizer and an environmental endocrine-disrupting compound. However, whether prenatal exposure to DBP can impair erectile function remains unknown. We conducted this study to investigate the potential effects of prenatal exposure to DBP on erectile function and the underlying mechanisms. A rat model of prenatal DBP exposure (12.5, 100 or 800 mg/kg/day by gavage during gestational days 13–21) was established. Prenatal DBP exposure significantly decreased penis/body weight ratio, myelin sheath thickness of cavernosum nerves and serum testosterone level in male rats at the age of 10 weeks. Furthermore, erectile dysfunction was detected in all DBP exposure groups, which exhibited substantial increases in transforming growth factor-β1 (TGF-β1) expression and decreases in the expression of alpha smooth muscle actin (α-SMA), neuronal and endothelial nitric oxide synthase (nNOS and eNOS). Additionally, the phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were remarkably lower, but the Bcl-2-associated X protein (Bax)/Bcl-2 ratio and caspase-3 were higher in DBP exposure groups than in the control group. Notably, prenatal exposure to DBP increase the risk of ED in male adult rats, even taking low dose of DBP (12.5 mg/kg/day). DBP exposure causing penile fibrosis, decreased testosterone level, and endothelial dysfunction may be responsible for ED by activating Akt/Bad/Bax/caspase-3 pathway and suppressing NOS/cGMP pathway in penis.

Dose- and time-effects responses of Nonylphenol on oxidative stress in rat through the Keap1-Nrf2 signaling pathway

Nonylphenol (NP) is a representative environmental endocrine-disrupting compound that can induce oxidative stress in organisms. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway acts an important role in preventing oxidative stress. The aim of this study was to investigate the influence of oxidative stress caused by NP on Keap1-Nrf2 pathway in rats. Rats were treated with NP (30, 90, 270 mg/kg) for different exposure time (7, 14 and 28 days). The levels of reactive oxygen species (ROS) in serum and glutathione S-transferase (GST), UDP-Glucuronosyl Transferase (UGT) in liver were detected by ELISA kits. Western blot was used to detect Keap1, Nrf2 protein expression in liver and cerebral cortex. The results showed that 28 days of NP exposure significantly increased ROS levels in NPH group. And 14 days exposure to NP significantly enhanced the levels of GST and UGT, while 28 days of exposure showed a suppressive effect. In liver, Keap1 levels was upregulated at 7, 14 and 28 days of NP exposure, while nuclear Nrf2 levels decreased at 7 and 28 days but increased at 14 days. In cerebral cortex, Keap1 and Nrf2 expression increased at 14 days but decreased at 28 days. Besides, with the prolongation of NP exposure time, the GST and UGT levels in NPM and NPH groups were increased firstly and then decreased, while Keap1 and Nrf2 protein levels were constantly decreased in liver and cerebral cortex. In conclusion, the lower dose and shorter exposure time of NP activated the Keap1-Nrf2 pathway that may reduce the damage of oxidative stress, but when further exposed to NP at higher dose and time, the pathway could be inhibited.

Long-term bisphenol A exposure exacerbates diet-induced prediabetes via TLR4-dependent hypothalamic inflammation

Bisphenol A (BPA), an environmental endocrine-disrupting compound, has been revealed associated with metabolic disorders such as obesity, prediabetes, and type 2 diabetes (T2D). However, its underlying mechanisms are still not fully understood. Here, we provide new evidence that BPA is a risk factor for T2D from a case-control study. To explore the detailed mechanisms, we used two types of diet models, standard diet (SD) and high-fat diet (HFD), to study the effects of long-term BPA exposure on prediabetes in 4-week-old mice. We found that BPA exposure for 12 weeks exacerbated HFD-induced prediabetic symptoms. Female mice showed increased body mass, serum insulin level, and impaired glucose tolerance, while male mice only exhibited impaired glucose tolerance. No change was found in SD-fed mice. Besides, BPA exposure enhanced astrocyte-dependent hypothalamic inflammation in both male and female mice, which impaired proopiomelanocortin (POMC) neuron functions. Moreover, eliminating inflammation by toll-like receptor 4 (TLR4) knockout significantly abolished the effects of BPA on the hypothalamus and diet-induced prediabetes. Taken together, our data establish a key role for TLR4-dependent hypothalamic inflammation in regulating the effects of BPA on prediabetes.

Long-term effects of in ovo exposure to an environmentally relevant dose of atrazine on the thyroid gland of Caiman latirostris

The increased incidence of human thyroid disorders, particularly in women, suggests that the exposure to endocrine-disrupting compounds (EDCs) together with sex-related factors could play a role in thyroid dysregulation. Since the herbicide atrazine (ATZ) is an environmental EDC suspected to behave as a thyroid disruptor, and Caiman latirostris is a crocodilian species highly sensitive to endocrine disruption that can be exposed to ATZ, this study aimed to describe the histoarchitecture and sexually dimorphic features of the thyroid gland of C. latirostris, and to determine the long-term effects of in ovo exposure to an environmentally relevant dose of ATZ (0.2 ppm) on its thyroid gland and growth. Control caimans showed no sexual dimorphisms. In contrast, ATZ-exposed caimans showed altered embryo growth but an unaltered temporal pattern of development and a sexually dimorphic response in the body condition index growth curves postnatally, which suggests a female-related increase in fat storage. Besides, both male and female exposed caimans showed increases in the size of the thyroid stromal compartment, content of interstitial collagen, and follicular hyperplasia, and decreases in the expression of androgen receptor in the follicular epithelium. ATZ-exposed females, but not males, also showed evidences of thyroid enlargement, colloid depletion, increased follicular epithelial height and increased presence of microfollicular structures. Our results demonstrate that prenatal exposure of caimans to ATZ causes thyroid disruption and that females were more vulnerable to ATZ than males. The effects were organizational and observed long after exposure ended. These findings alert on ATZ side-effects on the growth, metabolism, reproduction and development of non-target exposed organisms, particularly females.

The influence of long-term cadmium exposure on the male advertisement call of Xenopus laevis

Cadmium (Cd) is a non-essential environmental endocrine-disrupting compound found in water and a potential threat to aquatic habitats. Cd has been shown to have various short-term effects on aquatic animals; however, evidence for long-term effects of Cd on vocal communications in amphibians is lacking. To better understand the long-term effects of low-dose Cd on acoustic communication in amphibians, male Xenopus laevis individuals were treated with low Cd concentrations (0.1, 1, and 10μg/L) via aqueous exposure for 24months. At the end of the exposure, the acoustic spectrum characteristics of male advertisement calls and male movement behaviors in response to female calls were recorded. The gene and protein expressions of the androgen receptor (AR) were determined using Western blot and RT-PCR. The results showed that long-term Cd treatment affected the spectrogram and formant of the advertisement call. Compared with the control group, 10μg/L Cd significantly decreased the first and second formant frequency, and the fundamental and main frequency, and increased the third formant frequency. One and 10-μg/L Cd treatments significantly reduced the proportion of individuals responding to female calls and prolonged the time of first movement of the male. Long-term Cd treatment induced a downregulation in the AR protein. Treatments of 0.1, 1, and 10μg/L Cd significantly decreased the expression of AR mRNA in the brain. These findings indicate that long-term exposure of Cd has negative effects on advertisement calls in male X. laevis.

Environmental exposure to triclosan and polycystic ovary syndrome: a cross-sectional study in China

ObjectivesPolycystic ovary syndrome (PCOS) is the most common endocrinopathy of women at reproductive age. Although the aetiology of PCOS remains unclear, potential effects of environmental endocrine-disrupting compounds on the development...

Preconception paternal bisphenol A exposure induces sex-specific anxiety and depression behaviors in adult rats.

Bisphenol A (BPA), an environmental endocrine-disrupting compound, has drawn a great attention for its adverse effect on behavioral development. Maternal exposure to this compound has been reported to induce anxiety and depression in offspring, but the effect of its paternal exposure is rarely discussed. This study investigated whether preconception paternal BPA exposure can affect the emotions of male rats and their offspring. Eighteen adult male rats (F0) received either a vehicle or 50 μg/kg/day BPA diet for 21 weeks and were then mated with non-exposed females to produce offspring (F1). The affective behaviors of F0 and F1 rats were evaluated in the open-field test, the elevated-plus maze and the forced swimming test, and their serum corticosterone were then examined. BPA exposure induced increased anxiety behaviors along with increased serum corticosterone in F0 rats. This paternal exposure also led to increased anxiety behaviors in F1 females and aggravated depression behaviors in both sexes of F1 rats. Furthermore, only F1 females exhibited increased serum corticosterone. Overall, these data indicate that preconception paternal exposure to a low dose of BPA may induce transgenerational sex-specific impairments in the affection of adult rats.

Occurrence of phthalates in aquatic environment and their removal during wastewater treatment processes: a review.

Phthalates are plasticizers and are concerned environmental endocrine-disrupting compounds. Due to their extensive usage in plastic manufacturing and personal care products as well as the potential to leach out from these products, phthalates have been detected in various aquatic environments including drinking water, groundwater, surface water, and wastewater. The primary source of their environmental occurrence is the discharge of phthalate-laden wastewater and sludge. This review focuses on recent knowledge on the occurrence of phthalate in different aquatic environments and their fate in conventional and advanced wastewater treatment processes. This review also summarizes recent advances in biological removal and degradation mechanisms of phthalates, identifies knowledge gaps, and suggests future research directions.

Reversible Reduction of Estrone to 17β-Estradiol by , , and Isolates from the Las Vegas Wash.

Environmental endocrine-disrupting compounds (EDCs) are a growing concern as studies reveal their persistence and detrimental effects on wildlife. Microorganisms are known to affect the transformation of steroid EDCs; however, the diversity of estrogen-degrading microorganisms and the range of transformations they mediate remain relatively little studied. In mesocosms, low concentrations of added estrone (E1) and 17β-estradiol (E2) were removed by indigenous microorganisms from Las Vegas Wash water within 2 wk. Three bacterial isolates, sp. strain LVW-9, sp. strain LVW-12, and sp. strain LVW-PC, were enriched from Las Vegas Wash water on E1 and E2 and used for EDC transformation studies. In the presence of alternative carbon sources, LVW-9 and LVW-12 catalyzed near-stoichiometric reduction of E1 to E2 but subsequently reoxidized E2 back to E1; whereas LVW-PC minimally reduced E1 to E2 but effectively oxidized E2 to E1 after a 20-d lag. In the absence of alternative carbon sources, LVW-12 and LVW-PC oxidized E2 to E1. This report documents the rapid and sometimes reversible microbial transformation of E1 and E2 and the slow degradation of 17α-ethinylestradiol in urban stream water and extends the list of known estrogen-transforming bacteria to the genera and . These results suggest that discharge of steroid estrogens via wastewater could be reduced through tighter control of redox conditions and may assist in future risk assessments detailing the environmental fate of estrogens through evidence that microbial estrogen transformations may be affected by environmental conditions or growth status.

In vitro and in silico assessment of the structure-dependent binding of bisphenol analogues to glucocorticoid receptor.

Widespread use of bisphenol A (BPA) and other bisphenol analogues has attracted increasing attention for their potential adverse effects. As environmental endocrine-disrupting compounds (EDCs), bisphenols (BPs) may activate a variety of nuclear receptors, including glucocorticoid receptor (GR). In this work, the binding of 11 BPs to GR was investigated by fluorescence polarization (FP) assay in combination with molecular dynamics simulations. The human glucocorticoid receptor was prepared as a soluble recombinant protein. A fluorescein-labeled dexamethasone derivative (Dex-fl) was employed as tracer. Competitive displacement of Dex-fl from GR by BPs showed that the binding affinities of bisphenol analogues were largely dependent on their characteristic functional groups. In order to further understand the relationship between BPs structures and their GR-mediated activities, molecular docking was utilized to explore the binding modes at the atomic level. The results confirmed that structural variations of bisphenol analogues contributed to different interactions of BPs with GR, potentially causing distinct toxic effects. Comparison of the calculated binding energies vs. experimental binding affinities yielded a good correlation (R 2 = 0.8266), which might be helpful for the design of environmentally benign materials with reduced toxicities. In addition, the established FP assay based on GR exhibited the potential to offer an alternative to traditional methods for the detection of bisphenols.

Phthalate contamination in aquatic environment: A critical review of the process factors that influence their removal in conventional and advanced wastewater treatment

ABSTRACTPhthalates are dialkyl or alkyl aryl ester derivatives of phthalic acid and environmental endocrine-disrupting compounds. For their wide usage in plastic manufacturing and personnel care products as well as the potential to leach out from products, phthalates have been worldwide detected in aquatic environment. Phthalate-laden treated wastewater is among the main source of their environmental contamination. The authors provide a critical review of contamination level of phthalates in the aquatic environment including surface, ground and drinking water. The contamination level of phthalates is highest in wastewater followed by surface water, groundwater, and drinking water. A main source of phthalate contamination in aquatic sources is phthalate-laden wastewater treatment effluents. Therefore, process factors influencing their removal in conventional and advance oxidation processes (AOPs) of wastewater treatment are summarized in the review. Better removal of phthalates in conventional wastewater treatment is favored by enhanced solid separation, sludge retention time (15 days), hydraulic retention time (11 days), and a combination of redox environments. In AOPs, presence of organic matter, process coupling with adsorbents, and pH may influence the removal of phthalates. Overall this review can provide a collective background to conceive the extent of phthalate contamination in aquatic environment and recognize factors that may improve removal of phthalates and minimization of their release into the environment.

Wastewater treatment plant effluent alters pituitary gland gonadotropin mRNA levels in juvenile coho salmon (Oncorhynchus kisutch)

It is well known that endocrine disrupting compounds (EDCs) present in wastewater treatment plant (WWTP) effluents interfere with reproduction in fish, including altered gonad development and induction of vitellogenin (Vtg), a female-specific egg yolk protein precursor produced in the liver. As a result, studies have focused on the effects of EDC exposure on the gonad and liver. However, impacts of environmental EDC exposure at higher levels of the hypothalamic-pituitary-gonad axis are less well understood. The pituitary gonadotropins, follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) are involved in all aspects of gonad development and are subject to feedback from gonadal steroids making them a likely target of endocrine disruption. In this study, the effects of WWTP effluent exposure on pituitary gonadotropin mRNA expression were investigated to assess the utility of Lh beta-subunit (lhb) as a biomarker of estrogen exposure in juvenile coho salmon (Oncorhynchus kisutch). First, a controlled 72-h exposure to 17α-ethynylestradiol (EE2) and 17β-trenbolone (TREN) was performed to evaluate the response of juvenile coho salmon to EDC exposure. Second, juvenile coho salmon were exposed to 0, 20 or 100% effluent from eight WWTPs from the Puget Sound, WA region for 72h. Juvenile coho salmon exposed to 2 and 10ng EE2L⿿1 had 17-fold and 215-fold higher lhb mRNA levels relative to control fish. Hepatic vtg mRNA levels were dramatically increased 6670-fold, but only in response to 10ng EE2L⿿1 and Fsh beta-subunit (fshb) mRNA levels were not altered by any of the treatments. In the WWTP effluent exposures, lhb mRNA levels were significantly elevated in fish exposed to five of the WWTP effluents. In contrast, transcript levels of vtg were not affected by any of the WWTP effluent exposures. Mean levels of natural and synthetic estrogens in fish bile were consistent with pituitary lhb expression, suggesting that the observed lhb induction may be due to estrogenic activity of the WWTP effluents. These results suggest that lhb gene expression may be a sensitive index of acute exposure to estrogenic chemicals in juvenile coho salmon. Further work is needed to determine the kinetics and specificity of lhb induction to evaluate its utility as a potential indicator of estrogen exposure in immature fish.

Biotransformation of Endocrine Disrupting Compounds by Selected Phase I and Phase II Enzymes – Formation of Estrogenic and Chemically Reactive Metabolites by Cytochromes P450 and Sulfotransferases

The endocrine system is a major communication system in the body and is involved in maintenance of the reproductive system, fetal development, growth, maturation, energy production, and metabolism,. The endocrine system responds to the needs of an organism by secreting a wide variety of hormones that enable the body to maintain homeostasis, to respond to external stimuli, and to follow various developmental programs. This occurs through complex signalling cascades,with multiple sites at which the signals can be regulated. Endocrine disrupting compounds (EDCs) affect the endocrine system by simulating the action of the naturally produced hormones, by inhibiting the action of natural hormones, by changing the function and synthesis of hormone receptors, or by altering the synthesis, transport, metabolism, and elimination of hormones. It has been established that exposure to environmental EDCs is a risk factor for disruption of reproductive development and oncogenesis in both humans and wildlife. For accurate risk assessment of EDCs, the possibility of bioactivation through biotransformation processes needs to be included since neglecting these mechanisms may lead to undervaluation of adverse effects on human health caused by EDCs and/or their metabolites. This accurate risk assessment should include: (1) possibility of EDCs to be bioactivated into metabolites with enhanced endocrine disruption (ED) effects, and (2) possibility of EDCs to be biotransformed into reactive metabolites that may cause DNA damage. Here, we present an overview of different metabolic enzymes that are involved in the biotransformation of EDCs. In addition, we describe how biotransformation by Cytochromes P450 (CYPs), human estrogen sulfotransferase 1E1 (SULT1E1) and selected other phase II enzymes, can lead to the formation of bioactive metabolites. This review mainly focuses on CYP- and SULT-mediated bioactivation of estrogenic EDCs and summarizes our views on this topic while also showing the importance of including bioactivation and biotransformation processes for improved risk assessment strategies.

Androgen receptor activation by polychlorinated biphenyls

The exposure to environmental endocrine disrupting compounds (EDC), as polychlorinated biphenyls (PCBs), widely diffused in the environment may produce epigenetic changes that affect the endocrine system. We found that PCBs activate AR transcriptional activity and that this effect is potentiated by the demethylase Jarid1b, a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by PCB. The aim of the present study was to investigate the effect of the treatment of cultured cells (HEK293) with a mixture of the most diffused environmental PCBs and, also with dihydrotestosterone (DHT), on the functional interaction between AR and Jarid1b. Although the effect induced by DHT on the AR transactivation was considerably higher, the PCB mixture produced an AR-mediated transactivation in a dose-dependent manner. Cotransfection with plasmids expressing Jarid1b and various AR isoforms containing polyglutamine tracts (polyQ tracts) of different lengths showed that Jarid1b potentiates the AR transcriptional activity induced by PCBs but only with the shortest AR isoform. The potentiating effect of Jarid1b on the AR is mediated by a direct interaction of the enzyme with the AR promoter. In fact, utilizing constructs containing AR promoters with a different length and a luciferase reporter gene, we showed that the effect of PCBs, but not of DHT, needs the presence of Jarid1b and of at least two DNA binding sites for Jarid1b.