Xenoestrogens Research Articles

Determination of environmental estrogens and bisphenol A in water samples by ultra-high performance liquid chromatography coupled to Q-Exactive high resolution mass spectrometry after magnetic solid-phase extraction

A novel, simple and rapid method based on the magnetic solid-phase extraction (MSPE) combined with ultra-high performance liquid chromatography coupled to Q-Exactive high resolution mass spectrometry (UHPLC-Q-Exactive HRMS) was developed for the determination of bisphenol A, 17β-estradiol, dienestrol, hexestrol, and diethylstilbestrol in water samples. In this study, novel aldehyde group functionalized core-shell mesoporous silica magnetic nanoparticles were used as adsorbents for purification and enrichment of the environmental estrogens and bisphenol A for the first time. The main factors including desorption solvent, adsorbent amount, adsorption time and desorption time affecting the performance of MSPE procedure were investigated in detail. Linearities with determination coefficients higher than 0.998 were obtained for all the target compounds, and the mean recoveries were in the range of 81.7–96.3%. The intra-day and inter-day precision were satisfactory with the relative standard deviations in the range of 2.3–8.1% and 3.5–9.9%, respectively. The limits of detection were found between 0.2 and 3.0 ng/L. Finally, the developed MSPE-UHPLC-Q-Exactive HRMS method was successfully applied for determination of the environmental estrogens and bisphenol A in water samples.

Impact of Environmental Chemicals (Plasticizers) on Reproduction

Exposure to synthetic environmental chemicals (e.g., DDT and its metabolites, especially p,p`-DDE, alkylphenol ethoxylates, PCBs and dioxins) produces reproductive problems in a variety of vertebrate species via endocrine mechanisms. Naturally occurring environmental chemicals (e.g., phytoestrogens and estrogenic mycotoxins) induce infertility in domestic animal species and can alter human reproductive function. Concerns over these findings have been compounded by a series of publications suggesting that in utero exposure to environmental chemicals may have contributed to the reported decline in human sperm counts, the increased incidences of urogenital malformations (e.g., hypospadias, testicular cancer and undescended testes) and altered sex ratio over the last 40–50 years. It is postulated that in utero exposure to environmental estrogens could be responsible for the increased incidences of these alterations. This hypothesis is biologically plausible because hormones play critical roles as regulators of development in vertebrates and exposure to hormonally active toxicants during sexual differentiation is known to produce abnormal reproductive phenotypes in humans and other animals.

Estrone exposure interacts with temperature to alter predator evasion performance and systemic mRNA abundances

Environmental estrogens from anthropogenic activities are ubiquitous in aquatic ecosystems. Ambient temperature in these systems also fluctuates in daily, seasonal, and long-term rhythms. While both factors have been studied extensively, their interaction on aquatic life is critical to understand. The objective of this study was, therefore, to examine how behavior and gene expression are impacted by estrogenic exposure across a range of environmental temperatures. Larval fathead minnows (Pimephales promelas) were exposed to estrone (E1) at two concentrations (nominal 625 and 1250 ng/L) or to an ethanol solvent control, at one of four temperatures (15, 18, 21 and 24 °C) from fertilization to 21 days post-hatch. Exposed larvae were assessed for alterations in predator evasion performance and mRNA abundances of two genes for calcium channel receptors found in muscles - dihydropyridine receptor (dhpr) and ryanodine receptor 1, and the gonadal genes anti-Müllerian hormone, cytochrome P450 gonadal aromatase (cyp19a), doublesex and mab-3 related transcription factor 1 (dmrt1) and estrogen receptor 1 (esr1). Larval escape angle, escape latency, as well as systemic esr1 and cyp19a mRNA abundances were altered by an interaction between E1 concentration and temperature. E1-exposed larval exhibited reduced escape performance across all tested temperatures, whereas decreased systemic dhpr mRNA abundance was observed only at 18 °C. E1-exposure reduced systemic mRNA abundances of amh, cyp19a, dhpr, and ryr1, while temperature significantly reduced systemic cyp19a and dhpr mRNA abundances. E1-exposure and temperature significant enhanced systemic mRNA abundances of esr1 and cyp19a, respectively. These complex results illustrate the importance of considering how abiotic factors may moderate the effects of contaminant exposure during the sensitive larval developmental stage, as temperature modulates effects of estrogenic exposure on animal performance and mRNA abundances.

Estrogen receptor 1 expression and methylation of Esr1 promoter in mouse fetal prostate mesenchymal cells induced by gestational exposure to bisphenol A or ethinylestradiol.

Fetal/neonatal environmental estrogen exposures alter developmental programing of the prostate gland causing onset of diseases later in life. We have previously shown in vitro that exposures to 17β-estradiol (E2) and the endocrine disrupting chemical bisphenol A, at concentrations relevant to human exposure, cause an elevation of estrogen receptor α (Esr1) mRNA in primary cultures of fetal mouse prostate mesenchymal cells; a similar result was observed in the fetal rat urogenital sinus. Effects of these chemicals on prostate mesenchyme in vivo are not well understood. Here we show effects in mice of fetal exposure to the estrogenic drug in mixed oral contraceptives, 17α-ethinylestradiol (EE2), at a concentration of EE2 encountered by human embryos/fetuses whose mothers become pregnant while on EE2-containing oral contraceptives, or bisphenol A at a concentration relevant to exposures observed in human fetuses in vivo. Expression of Esr1 was elevated by bisphenol A or EE2 exposures, which decreased the global expression of DNA methyltransferase 3A (Dnmt3a), while methylation of Esr1 promoter was significantly increased. These results show that exposures to the environmental estrogen bisphenol A and drug EE2 cause transcriptional and epigenetic alterations to expression of estrogen receptors in developing prostate mesenchyme in vivo.

Effects of nonylphenol administration on serum, liver and testis estrogen metabolism

PurposeNonylphenol (NP) is one widely distributed representative of environmental estrogens that disturb reproductive activities, bone metabolism and brain function through interfering diverse signal pathways leading to hormone metabolic dysfunctions, immunologic derangement, and tumorigenesis. Few of previous studies have observed the subacute toxicity on rodents, and little has been focused on the mechanism underneath the toxicities observed. MethodsThe 32 male Sprague-Dawley (SD) rats were randomly divided into four groups, the negative control group (corn oil) NP low, medium and high dose groups [30, 90, 270 mg/(kg·d)]. SD rats administrated with different dosage of NP every other day for 28d. Elisa and RT-PCR was employed to observe estrogen metabolism markers or mRNA expressions. ResultsIn serum, NP exposure caused testosterone (T) (p < 0.001), progesterone (PROG) (p < 0.05) and estrone (E1) (p < 0.05) increased. In testicle, NP exposure caused T (p < 0.001), PROG (p < 0.05), E1 (p < 0.05), 17β-estradiol (E2) (p < 0.05) and ERα mRNA (p < 0.01) increased, while P450 aromatizing enzyme (p < 0.001) decreased in NPL and ERβ mRNA (p < 0.001) decreased in NPM and NPH. In liver, NP exposure caused 17β-HSD2 mRNA (p < 0.01) increased, while P450 aromatizing enzyme decreased (p < 0.05). ConclusionNP exposure exhibited general and estrogenic toxicity in rats through disturbing estrogen secretion network and estrogen receptor expression network, inducing abnormal metabolism of estrogen, whether in serum, liver and testicle.

Effect of biochar amendment on sorption-desorption and dissipation of 17α‑ethinylestradiol in sandy loam and clay soils

Animal manure application in agricultural land has caused the release of steroid estrogens in the soil environment and further movement to aquatic systems. The objective of this study was to investigate the effects of biochar addition on sorption-desorption and dissipation behaviors of 17α‑ethinylestradiol (EE2) in two different textured soils. A Commerce sandy loam and a Shakey clay were selected and subjected to sterilization. Soil samples with and without sterilization were reacted with a series of EE2 solutions of different concentrations for sorption followed by desorption and quantification using HPLC-MS/MS. Long-term dissipation of EE2 in the same soils was also evaluated over a 30-d incubation. Biochar amendment increased the maximum EE2 sorption capacity but decreased its water desorption in both sandy loam and clay soils. On other hand, biochar addition increased the Koc in the clay soil which had low EE2 sorption efficiency but decreased Koc in the sandy loam which had high EE2 sorption efficiency. Biochar did significantly increase both desorbable and non-extractable fractions of EE2, while it reduced the bioavailability of EE2 to microbial degradation. The dissipation of EE2 in non-sterilized soils fit to the first-order kinetic model, whereas it was better described by zero-order kinetic for sterilized soil. Biochar increased the half-life of EE2 dissipation in non-sterilized Commerce sandy loam soil by 48% (from 3.63 to 5.37 d) and in non-sterilized Sharkey clay soil by 67% (from 2.28 to 3.81 d). Overall, this study demonstrated positive impacts of biochar on the retention of estrogen hormones in soils.

New methods for purification of Paralichthys olivaceus lipovitellin and immunoassay-based detection of vitellogenin

Increasing levels of estrogenic pollution in marine environments has made the development of reliable biological detection techniques urgently needed. In this study, Japanese flounder (Paralichthys olivaceus) lipovitellin (Lv) was purified and used to establish three immunological methods for the detection of vitellogenin (Vtg), a biomarker for environmental estrogens. Firstly, five different methods were employed to purify Lv, among which water-precipitation was the fastest and easiest way to purify Lv. Japanese flounder Lv was characterized as a phospholipoglycoprotein with a molecular weight of ∼369 kDa. Using purified Lv and its specific polyclonal antibody, a sandwich enzyme-linked immunosorbent assay (ELISA) was developed. This assay had a working range from 7.8 to 250 ng/mL and a detection limit of 3.1 ng/mL. Furthermore, we developed an immunohistochemistry (IHC) and an immunofluorescence (IF) assay, both of which allowed visual detection of liver Vtg. Finally, Vtg induction in plasma and liver of juvenile Japanese flounders exposed to 17β-ethinylestradiol (EE2) was measured using these three methods. Exposure to 10 and 50 ng/L EE2 significantly increased plasma Vtg levels, and obvious positive fluorescence signals were observed near the liver sinusoidal vessels. These results confirmed that the methods developed effectively detected estrogenic activity of exogenous chemicals. Therefore, this study provides reliable methodologies for biomonitoring of estrogenic pollution in marine environments.

Bare polyprolylene hollow fiber as extractive phase for in-tube solid-phase microextraction to determine estrogens in water samples.

Polypropylene hollow fibers as the adsorbent were directly filled into a polyetheretherketone tube for in-tube solid-phase microextraction. The surface properties of hollow fibers were characterized by a scanning electron microscope. Combined with high performance liquid chromatography, the extraction tube showed good extraction performance for five environmental estrogen hormones. To achieve high analytical sensitivity, four important factors containing sampling volume, sampling rate, content of organic solvent in sample, and desorption time were investigated. Under the optimum conditions, an online analysis method was established with wide linear range (0.03-20µg/L), good correlation coefficients (≥0.9998), low limits of detection (0.01-0.05µg/L), low limits of quantitation (0.03-0.16µg/L), and high enrichment factors (1087-2738). Relative standard deviations (n=3) for intraday (≤3.6%) and interday (≤5.1%) tests proved the stable extraction performance of the material. Durability and chemical stability of the extraction tube were also investigated, relative standard deviations of all analytes were less than 5.8% (n=3), demonstrating the satisfactory stability. Finally, the method was successfully applied to detect estrogens in real samples.

Genome-Wide Analysis of Low Dose Bisphenol-A (BPA) Exposure in Human Prostate Cells.

Endocrine disrupting compounds (EDCs) have the potential to cause adverse effects on wild-life and human health. Two important EDCs are the synthetic estrogen 17α-ethynylestradiol (EE2) and bisphenol-A (BPA) both of which are xenoestrogens (XEs) as they bind the estrogen receptor and dis-rupt estrogen physiology in mammals and other vertebrates. In the recent years the influence of XEs on oncogenes, specifically in relation to breast and prostate cancer has been the subject of considerable study.Methodology: In this study, healthy primary human prostate epithelial cells (PrECs) were exposed to environmentally relevant concentrations of BPA (5nM and 25nM BPA) and interrogated using a whole genome microarray.Results: Exposure to 5 and 25nM BPA resulted in 7,182 and 7,650 differentially expressed (DE) genes, respectively in treated PrECs. Exposure to EE2 had the greatest effect on the PrEC transcriptome (8,891 DE genes).Conclusion: We dissected and investigated the nature of the non-estrogenic gene signature associated with BPA with a focus on transcripts relevant to epigenetic modifications. The expression of transcripts encoding nuclear hormone receptors as well as histone and DNA methylation, modifying enzymes were significantly perturbed by exposure to BPA.

The effects of urbanization and rainfall on the distribution of, and risks from, phenolic environmental estrogens in river sediment

There is increasing concern about phenolic environmental estrogens (PEEs) in river systems, especially in economically developed regions, because of their potential to impact ecological systems. We studied the distribution of, ecological risks from, and factors that influenced PEEs in the sediments from the Duliujian River in the Beijing-Tianjin-Hebei Urban Agglomeration and the Pearl River in Guangdong Province in China. The three target PEEs, nonyl phenol (4-NP), octyl phenol (4-t-OP), and bisphenol A (BPA), were detected in the sediments at concentrations ranging from 204.4 to 12604.3, 32.6 to 297.3, and from 12.8 to 298.4 ng g−1 in the Pearl River, and from 153.5 to 3614.9, 90.7 to 990.0, and 83.5–913.3 ng g−1 in the Duliujian River, respectively. The PEE concentrations were significantly and positively correlated with total organic carbon in the river sediments (p < 0.1). Urbanization influenced the distribution of PEEs and applications and discharges of PEEs were associated with large populations and industries. Rainfall and wastewater discharge patterns also influenced how PEEs were distributed in river sediments. The potential ecological risks from 4-NP, 4-t-OP, and BPA in these two rivers were high. Measures should be put in place to control the transport and storage of these compounds in river systems.

MON-034 Novel Estrogen Activity and Gene Regulation Induced by Personal Care Products in Breast Cancer Cells

The contribution of personal care product (PCP) use to hormone regulated cancer and cancer disparities is unknown. Considering that environmental estrogens and endocrine disrupting chemicals (EDCs) have the potential to contribute to cancer promotion and progression, evaluating chronic use PCPs and hair products for estrogen activity may be of use for risk assessment. In this study, we tested the hypothesis that the ethanol extracts of 11 PCPs (including hair products) would induce estrogen agonist or antagonist activity in breast cancer cells in culture. We have previously shown that three of these PCP extracts induce estrogen agonist activity in the MCF-7 E3 estrogen proliferation assay while six extracts induce estrogen antagonist effects in the T47dkbluc estrogen reporter gene assay. In the current study, the LanthaScreen TR-FRET ER Alpha Competitive Binding Assay was employed to confirm that all nine estrogenic PCP extracts bind to the ER with up to 85% of the activity of E2. Then, to compare endogenous gene regulation induced by the estrogenic PCP extracts with treatment with E2, the Qiagen RT2 Profiler PCR Array for Human Estrogen Receptor Signalling was utilized. MCF-7 cells were treated with solvent control, 1 nM E2 or one of the nine PCP extracts shown to have estrogen activity in bioassays. The three extracts with agonist activity in bioassays produced a gene activation pattern similar to E2 with fewer total genes induced. At the same time, these extracts had no effect on some genes E2 inhibited (compared to control). While the extracts with estrogen antagonist activity in the bioassays inhibited the transcription of most genes induced by E2, these extracts activated the transcription of a number of genes E2 either down regulated or did not regulate. The antagonist PCP extracts repressed transcription of as many as 20 genes such as GPER1, PGR, NR5A2, CAV1 relative to E2. At the same time, in contrast to E2, these extracts induced the transcription of genes such as CYP1A1, CKB, CTGF, WNT4, CTGF, S100A6, FST, NCOA1 CTGF, S100A6, FST, NCOA1, APBB1, PTCH1, MAFF, WNT5A, and/or NOV. We conclude that chronic exposure to these estrogenic or antiestrogenic PCPs has the potential to impact estrogen mediated signaling in exposed individuals that exposure may have an influence on the proliferation and survival of estrogen dependent cancer.

Bisphenol A disrupts mitotic progression via disturbing spindle attachment to kinetochore and centriole duplication in cancer cell lines

Bisphenol A [BPA, 2,2-bis-(4-hydroxyphenyl)propane] is one of the most prevalent synthetic environmental estrogens; as an endocrine disruptor, it is associated with endocrine-related cancers including breast, ovarian, and prostate. However, the mechanisms by which BPA contributes to carcinogenesis are unclear. This study aims to clarify its toxic effects on mitotic cells and investigate the molecular mechanism. In vitro effects of BPA on mitotic progression were examined by performing experiments on HeLa cells. Proteins involved in mitotic processes were detected by Western blot, live cell imaging, and immunofluorescence staining. The results showed that BPA increased chromosomal instability by perturbing mitotic processes such as bipolar spindle formation and spindle microtubule attachment to the kinetochore. BPA prolonged mitotic progression by disturbing spindle attachment and concomitant activating spindle assembly checkpoint (SAC). Mechanistically, BPA interfered proper localization of HURP to the proximal ends of spindle microtubules, Kif2a to the minus ends of spindle microtubules, and TPX2 on the mitotic spindle. This mislocalization of microtubule associated proteins (MAPs) is postulated to lead to spindle attachment failure. Furthermore, BPA caused multipolar spindle by inducing centriole overduplication and premature disengagement. Although BPA acts as an estrogen receptor (ER) agonist, mitotic defects caused by BPA occurred in an ER-independent manner. Our findings indicate that BPA may stimulate carcinogenesis not only by acting as an endocrine disruptor but also by increasing chromosomal instability during mitosis.

Bisphenol A and 17α-ethinylestradiol-induced transgenerational differences in expression of osmoregulatory genes in the gill of medaka (Oryzias latipes)

Embryonic bisphenol A (BPA) and 17α-ethinylestradiol (EE2) exposure can have far reaching health effects in fish, including adult onset transgenerational reproductive abnormalities, anxiety, and cardiac disorders. It is unknown whether these two environmental estrogens can induce transgenerational abnormalities in the gill. The present study examined transgenerational effects of BPA or EE2 exposure on genes that are critical for osmoregulation in fish. Medaka (Oryzias latipes) embryos were exposed to either BPA (100 μg/L) or EE2 (0.05 μg/L) for the first 7 days of embryonic development and never thereafter for the remainder of that generation (F0) and in subsequent generations of this study (F1, F2, and F3). Expression of osmoregulatory genes (NKAα1a, NKAα1b, NKAα1c, NKAα3a, NKAα3b, NKCC1a, and CFTR) were examined in gills of the first-generation (F0) adults which were directly exposed as embryo and in the fourth-generation adults (F3), which were never exposed to either of these environmental estrogens. Significant alterations in expression of osmoregulatory genes were observed in both F0 and F3 generations. Within the F0 generation, a sex-specific expression pattern was observed with a downregulation of osmoregulatory genes in males and an upregulation of osmoregulatory genes in females. At the F3 generation, this pattern reversed with the majority of the osmoregulatory genes upregulated in males and downregulated in females, suggesting that exposure to BPA and EE2 during embryonic development induced transgenerational impairment in molecular events associated with osmoregulatory functions in subsequent generations. These adverse outcomes may have impacts on physiological functions related to osmoregulation of fish inhabiting contaminated aquatic environments.

Endocrine disrupting-chemicals and biochemical recurrence of prostate cancer after prostatectomy: A cohort study in Guadeloupe (French West Indies).

Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer (PCa). Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized PCa. We analyzed the relationship between exposure to the estrogenic chlordecone, the antiandrogenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the nondioxin-like polychlorinated biphenyl congener 153 (PCB-153) with mixed estrogenic/antiestrogenic properties and the risk of biochemical recurrence (BCR) after surgery. After a median follow-up of 6.1 years after surgery, we found a significant increase in the risk of BCR, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% confidence interval: 1.39-4.56 for the highest vs. lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB-135. These results shown that exposure to environmental estrogens may negatively influence the outcome of PCa treatment.

Prenatal exposure to Bisphenol‐F followed by chronic estrogen exposure in adulthood increases systolic blood pressure in female rats

Endocrine disrupting chemicals (EDCs) such as bisphenols and phthalates are produced in high volume in the US and all over the world. They are capable of leaching out of plastics and entering the food chain. They produce a variety of effects on the body, but not all effects are understood. Epidemiological evidence indicates that there is a marked increase in the incidence of hypertension and pre‐hypertension in young children. We hypothesized that exposure to these EDCs during pregnancy can affect brain circuits and cause high blood pressure in offspring. The risk is even greater for female offspring who are subsequently exposed to an environmental estrogen or oral contraceptives in adulthood. To test this, we exposed pregnant Sprague Dawley dams to saline, or 1μg/kg BW of bisphenol‐F (BPF). Two female offspring from each dam were either sham implanted or implanted with estradiol‐17β (E2) pellets that were capable of releasing 20 ng of E2/day for 90 days. Animals were also implanted with a telemeter (Data Sciences International; HD‐S10) in the femoral artery and were allowed to recover. Blood pressure recordings were obtained for once a week for 12 weeks over a 24‐hour time period. In control rats that were treated with E2, there was a modest increase in systolic BP. When prenatal BPF exposure was followed by exposure to E2 in adulthood, it produced a greater increase in systolic BP (p = 0.0031 during the day; p= 0.0081 at night). In contrast, prenatal BPF exposure followed by sham implantation resulted in marked increases in diastolic BP. These results indicate that prenatal exposure to BPF can increase BP in female rats. This risk is augmented when females are subjected to chronic low dose E2 exposure in adulthood. Further studies are needed to understand the underlying mechanisms.Support or Funding InformationSupported by UGA research foundation and start‐up funds.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of Environmental Estrogen on Lung Cancer Cell

Effects of Environmental Estrogen on Lung Cancer Cell

BPA disrupts the cardioprotection by 17β-oestradiol against ischemia/reperfusion injury in isolated guinea pig hearts

Bisphenol A (BPA) is an environmental oestrogen or xenoestrogen (XEs). XEs represent a health risk due to their potential for endocrine disruption and ability to mimic estrogenic activity. The effects of BPA on isolated hearts under normal and ischemia/reperfusion (I/R) conditions were investigated for the first time, with a focus on the effects of BPA and 17β-oestradiol (E2) co-administration on I/R injury. Our results indicated that BPA at 10−7 M and 10−5 M did not significantly affect heart rate (HR), coronary flow (CF), lactate dehydrogenase (LDH) or creatine kinase (CK) release in normal or I/R isolated hearts within the 90 min. However, E2 exerted a protective effect against I/R injury, whereas, BPA inhibited the cardio-protective effects of E2 on HR, CF, and LDH and CK release. Furthermore, BPA in combination with E2 aggravated I/R injury by increasing infarct size and causing a more severe ultrastructural disruption as compared to treatment with E2 alone. Based on our results, we conclude that BPA inhibits the cardio-protective effects of E2 on I/R-injured hearts, despite not significantly affecting normal or I/R isolated hearts.

Removal of 17β-estradiol from secondary wastewater treatment plant effluent using Fe3+-Saturated montmorillonite

Estrogens are of environmental concern because disruptive effect on biological functions at levels as low as ng/L. Wastewater treatment plant effluent is a significant source of estrogens in aquatic environment. Ferric ions (Fe3+)-saturated montmorillonite has been shown to effectively remove 17β-estradiol (βE2), a common estrogen, from pure water by catalyzing formation of insoluble βE2 oligomers on mineral surfaces. We investigated the effects of reaction temperature, dissolved organic matter, pH, and common cations, on Fe3+-saturated montmorillonite-surface catalyzed βE2 polymerization, and the removal of this estrogen from three different secondary wastewater effluents with more complicated matrixes. Highest βE2 removal occurred at near neutral pH and it increased with increasing treatment temperatures. Presence of common cations in the water did not affect the reaction efficiency. Dissolved organic matter at 15 mg C/L slightly lowered the βE2 removal efficiency as compared to that in pure water. Regardless of the source of wastewater effluents, βE2 removal efficiency of ∼40% was achieved using the dosage of Fe3+-saturated montmorillonite similar to that tested for the aqueous phases with simpler matrix. Doubling this dosage resulted in removal of ∼80% of βE2 from a tested secondary wastewater effluent within 30 min reaction. For wastewater with complex matrixes at the commonly reported βE2 levels which are magnitudes lower than the tested concentration in our study, this dosage would provide sufficient available reaction sites for the surface-catalyzed βE2 polymerization. This study demonstrated that Fe3+-saturated montmorillonite is a promising material for effective removal of phenolic estrogen compounds from domestic wastewater effluents.

Computational insights on agonist and antagonist mechanisms of estrogen receptor α induced by bisphenol A analogues

Structural analogues of bisphenol A (BPA) have become widely used as alternatives in BPA-free products. Most toxicological investigations have focused on the estrogenic activities of these analogues, which have been considered as potential environmental estrogens. However, recent studies revealed that certain BPA analogues could dramatically inhibit the proliferation of breast cancer cells, and exhibited strong anti-estrogenic effects compared with the antagonist 4-hydroxytamoxifen (OHT). Thus, we adopted computational models combining molecular dynamics simulations and binding free energy calculations to explore the underlying molecular basis of BPA analogues binding to estrogen receptor α (ERα). We also evaluated ligand-induced structural rearrangements of ERα at the atomic level. Conformational analyses showed that induced-fit H-bonding recognition by Thr347 was an important factor distinguishing antagonist from agonist BPA analogues. Moreover, antagonists of BPA analogues could indirectly induce the structural reposition of key helix 12 and produce an antagonistic conformation of ERα. Compared with OHT, the binding affinity of BPA analogues is stronger for antagonists than agonists. Taken together, we therefore propose computational indicators for screening of anti-estrogenic activities of BPA analogues, which may be beneficial for predicting the estrogenic or anti-estrogenic effects of BPA alternatives.

Upconversion fluorescent aptasensor for bisphenol A and 17β-estradiol based on a nanohybrid composed of black phosphorus and gold, and making use of signal amplification via DNA tetrahedrons.

This study describes an upconversion fluorescent aptasensor based on black phosphorus nanohybrids and self-assembled DNA tetrahedrons dual-amplification strategy for rapid detection of the environmental estrogens bisphenol A (BPA) and 17β-estradiol (E2). Tetrahedron complementary DNAs (T-cDNAs) were self-assembled in an oriented fashion on a 2D nanohybrid composed of black phosphorus (BP) and gold to give a materials of architecture BP-Au@T-cDNAs. In parallel, core-shell upconversion nanoparticles were modified with aptamers (UCNPs@apts) and used as capture probes. On complementary pairing, the BP-Au@T-cDNA quench the fluorescence of UCNPs@apts (measured at an excitation wavelength 808nm and at main emission peaks at 545nm and 805nm.) Compared with single-stranded probes based on black phosphorus and gold, the dual-amplification strategy increases quenching efficiency by nearly 25%-30% and reduces capture time to 10min. This is due to thehigher optical absorption of 2D nanohybrid and the reduction of steric hindrance by T-cDNAs. Exposure to BPA or E2 cause the release of UCNPs@apts from the BP-Au@T-cDNAs due to stronger binding between aptamer and analyte. Hence, fluorescence recovers at 545nm for BPA and 805nm for E2. Based on these findings, a dually amplified aptamer assay was constructed that covers the 0.01 to 100ngmL-1 BPA concentration range, and the 0.1 to 100ngmL-1 E2 concentration range. The detection limits are 7.8pgmL-1 and 92pgmL-1, respectively. This method was applied to the simultaneous determination of BPA and E2 in spiked samples of water, food, serum and urine. Graphical abstract Schematic presentation of novel quenching probes designed by tetrahedron complementary DNAs oriented self-assembled on the surface ofblack phosphorus/gold nanohybrids. Combined with aptamer-modified upconversion nanoparticles, a dual-amplification self-assembled fluorescence nanoprobe was constructed for simultaneous detection of BPA and E2.