Xenoestrogens Research Articles

Bisphenol AF Promoted the Growth of Uterus and Activated Estrogen Signaling Related Targets in Various Tissues of Nude Mice with SK-BR-3 Xenograft Tumor.

Environmental estrogens can promote the growth, migration, and invasion of breast cancer. However, few studies evaluate adverse health impacts of environmental estrogens on other organs of breast cancer patients. Therefore, the present study investigated the effects of environmental estrogen bisphenol AF (BPAF) on the main organs of female Balb/cA nude mice with SK-BR-3 xenograft tumor by detecting the organ development and gene expression of targets associated with G protein-coupled estrogen receptor 1 (GPER1)-mediated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways in hypothalamus, ovary, uterus, liver, and kidney. The results showed that BPAF at 20 mg/kg bw/day markedly increased the uterine weight and the uterine coefficient of nude mice compared to SK-BR-3 bearing tumor control, indicating that BPAF promoted the growth of uterus due to its estrogenic activity. Additionally, BPAF significantly up-regulated the mRNA relative expression of most targets related to nuclear estrogen receptor alpha (ERα) and GPER1-mediated signaling pathways in the hypothalamus, followed by the ovary and uterus, and the least in the liver and kidney, indicating that BPAF activated different estrogen activity related targets in different tissues. In addition, BPAF markedly up-regulated the mRNA expression of GPER1 in all tested tissues, and the molecular docking showed that BPAF could dock into GPER1. Because gene change is an early event of toxicity response, these findings suggested that BPAF might aggravate the condition of breast cancer patients through exerting its estrogenic activity via the GPER1 pathway in various organs.

Genome and transcriptome of Chinese medaka (Oryzias sinensis) and its uses as a model fish for evaluating estrogenicity of surface water

Ecological toxicity assessments of contaminants in aquatic environments are of great concern. However, a dilemma in ecological toxicity assessments often arises when linking the effects found in model animals in the laboratory and the phenomena observed in wild fishes in the field due to species differences. Chinese medaka (Oryzias sinensis), widely distributed in East Asia, is a satisfactory model animal to assess aquatic environment in China. Here, we domesticated this species and assembled its genome (814 Mb) using next-generation sequencing (NGS). A total of 21,922 high-confidence genes with 41,306 transcripts were obtained and annotated, and their expression patterns in tissues were determined by RNA-sequencing. Six mostly sensitive biomarker genes, including vtg1, vtg3, vtg6, zp3a.2, zp2l1, and zp2.3 to estrogen exposure were screened and validated in the fish exposed to concentrations of estrone (E1), 17β-estradiol (E2), and estriol (E3) under laboratory condition. Field investigations were then performed to evaluating the gene expression of biomarkers in wild Chinese medaka and levels of E1, E2, and E3 in the fish habitats. It was found that in 40 sampling sites, the biomarker genes were obviously highly expressed in the wild fish from about half sites, and the detection frequencies of E1, E2, and E3, were 97.5%, 42.5%, and 45% with mean concentrations of 82.48, 43.17, 52.69 ng/L, respectively. Correlation analyses of the biomarker gene expressions in the fish with the estrogens levels which were converted to EEQs showed good correlation, indicating that the environmental estrogens and estrogenicity of the surface water might adversely affect wild fishes. Finally, histologic examination of gonads in male wild Chinese medaka was performed and found the presence of intersex in the fish. This study facilitated the uses of Chinese medaka as a model animal for ecotoxicological studies.

Transcriptome analysis of changes in M. aeruginosa growth and microcystin production under low concentrations of ethinyl estradiol

Ethinyl estradiol (EE2) is a synthetic environmental estrogen with considerable estrogenic activity. It has been found to consequently pose a significant threat to the aquatic ecosystem. Harmful algal blooms are a major aquatic ecological issue. However, the relationship between EE2 and cyanobacterial bloom is mainly unknown. In this study, the physiological and molecular responses of Microcystis aeruginosa to EE2 exposure were investigated. A low level of EE2 (0.02 μg/L) significantly enhanced the growth of algal cells (P < 0.05), whereas higher concentrations of EE2 (0.2–200 μg/L) inhibited it. EE2 at doses ranging from 0.02 to 200 μg/L promoted the production of microcystins (MCs), with genes mcyABD playing a key role in the regulation of MC synthesis. The alterations of chlorophyll–a, carotenoid, and phycocyanin contents caused by EE2 showed the same trend as cell growth. At the molecular level, 200 μg/L EE2 significantly down–regulated genes in photosynthetic pigment synthesis, light harvesting, electron transfer, NADPH, and ATP generation. High concentrations of EE2 caused oxidative damage to algal cells on the 4th d. After 12d exposure, although there was no significant change in superoxide dismutase (SOD) content and no damage observed in membrane lipids, genes related to SOD and glutathione were changed. In addition, due to the down–regulation of pckA, PK, gltA, nrtA, pstS, etc., carbon fixation, glycolysis, TCA cycle, nitrogen and phosphorus metabolism were hindered by EE2 (200 μg/L). Gene fabG in fatty acid biosynthesis was significantly up–regulated, promoting energy storage in cells. These findings provide important clues to elucidate the effects and mechanisms of cyanobacterial blooms triggered by EE2 and help to effectively prevent and control cyanobacterial blooms.

Effects of bisphenol A on uterine leiomyoma: In vitro and in vivo evaluation with mechanistic insights related to XBP1

The incidence rate of human uterine leiomyomas is over 70% in the women of childbearing age, which has caused serious health and financial burden. Our previous study confirmed that Bisphenol A (BPA)，representative environmental estrogen, promoted the proliferation of human uterine leiomyomas and up-regulated the expression of cell proliferation-related genes. In this study, by combining ChIP-seq and RNA-seq, it was shown that after BPA intervention, H3K27ac modification levels and gene expression levels were altered in uterine leiomyomas cells. Moreover experimental verification found that BPA can regulate ITGA2 through the transcription factor XBP1, activate the downstream PI3K/AKT signaling pathway, eventually promote the proliferation of uterine leiomyomas. The present study provides new insights into the pathogenesis associated with exposure to BPA and other endocrine disruptors with similar effects by defining XBP1 as an important regulator, and which may act as an intervention and treatment target for uterine leiomyomas.

Xenobiotic estradiol-17ß alters gut microbiota of hatchling American alligators (Alligator mississippiensis).

Environmental oestrogens pose serious concerns for ecosystems through their effects on organismal survival and physiology. The gut microbiome is highly vulnerable to environmental influence, yet the effects of oestrogens on gut homeostasis are unknown because they are poorly studied in wildlife populations. To determine the influence of environmental oestrogens (i.e., xenoestrogens) on the diversity and abundance of gut microbiota, we randomly assigned 23 hatchling American alligators (Alligator mississippiensis) to three ecologically relevant treatments (control, low, and high oestrogen concentrations) for 10 weeks. We predicted that xenoestrogen exposure would decrease microbial diversity and abundance within the digestive tract and that this effect would be dose-dependent. Microbial samples were collected following diet treatments and microbial diversity was determined using 16S rRNA gene-sequencing. Individuals in oestrogen-treatment groups had decreased microbial diversity, but a greater relative abundance of operational taxonomic units than those in the control group. In addition, this effect was dose-dependent; as individuals were exposed to more oestrogen, their microbiome became less diverse, less rich and less even. Findings from this study suggest that oestrogen contamination can influence wildlife populations at the internal microbial-level, which may lead to future deleterious health effects.

The response of electrochemical method to estrogen effect and the tolerance to culture factors: Comparison with MTT and cell counting methods

Estrogen substances in the environment are increasing dramatically, which interfere with the normal hormone level of human body, lead to the disorder of endocrine system and even cancer. It is difficult to screen a large number of environmental estrogen substances by existing estrogen effect detection methods, and the results are often affected by many factors, thus the development of new method has become an urgent task. Electrochemical method is promising to reflect cell proliferation by tracking intracellular purine bases directly. In this study, the estrogen level in MCF-7 cells on multiwall carbon nanotubes modified glassy carbon electrode (MWCNTs/GCE) could be tracked simply and conveniently, and the estrogen effect of estradiol could be reflected by electrochemistry in time and dose-dependent manners. Electrochemical method displayed the best tolerance to culture factors, such as different cell densities, serum types, culture medium types and serum estrogen-free methods, which responsed to estrogen effect higher than MTT (about 40%) and cell counting methods (about 50%). Further Western blotting analysis showed that the estrogen effect of estradiol promoted purine catabolism and up-regulated guanine deaminase (GDA) and adenine deaminase (ADA) expression, the key enzymes of purine catabolism pathway, in a dose-dependent manner. The up-regulation of GDA and ADA led to the increase of intracellular guanine and xanthine, which enhanced the electrochemical signal derived from guanine and xanthine.

Effects of Dietary Resveratrol, Bile Acids, Allicin, Betaine, and Inositol on Recovering the Lipid Metabolism Disorder in the Liver of Rare Minnow Gobiocypris rarus Caused by Bisphenol A.

The fatty liver is one of the main problems in aquaculture. In addition to the nutritional factors, endocrine disrupter chemicals (EDCs) are one of the causes of fatty liver in fish. Bisphenol A (BPA) is a plasticizer widely used in the production of various plastic products and exhibits certain endocrine estrogen effects. Our previous study found that BPA could increase the accumulation of triglyceride (TG) in fish liver by disturbing the expression of lipid metabolism-related genes. How to recover the lipid metabolism disorder caused by BPA and other environmental estrogens remains to be explored. In the present study, Gobiocypris rarus was used as a research model, and 0.01% resveratrol, 0.05% bile acid, 0.01% allicin, 0.1% betaine, and 0.01% inositol were added to the feed of the G. rarus that exposed to 15 μg/L BPA. At the same time, a BPA exposure group without feed additives (BPA group) and a blank group with neither BPA exposure nor feed additives (Con group) were setted. The liver morphology, hepatosomatic index (HSI), hepatic lipid deposition, TG level, and expression of lipid metabolism-related genes were analyzed after 5 weeks of feeding. The HSI in bile acid and allicin groups was significantly lower than that in Con group. The TG in resveratrol, bile acid, allicin, and inositol groups returned to Con level. Principal component analysis of TG synthesis, decomposition, and transport related genes showed that dietary bile acid and inositol supplementation had the best effect on the recovery of BPA-induced lipid metabolism disorder, followed by allicin and resveratrol. In terms of lipid metabolism-related enzyme activity, bile acid and inositol were the most effective in recovering BPA-induced lipid metabolism disorders. The addition of these additives had a restorative effect on the antioxidant capacity of G. rarus livers, but bile acids and inositol were relatively the most effective. The results of the present study demonstrated that under the present dosage, bile acids and inositol had the best improvement effect on the fatty liver of G. rarus caused by BPA. The present study will provide important reference for solving the problem of fatty liver caused by environmental estrogen in aquaculture.

Environmental estrogens inhibit insulin-like growth factor (IGF) receptor mRNA expression, IGF binding, and IGF signaling ex vivo in rainbow trout (Oncorhynchus mykiss)

In this study, we used juvenile rainbow trout to examine the direct effects of selected environmental estrogens (EE), specifically, 17 β-estradiol (E2), β-sitosterol (βS), and 4-n-nonylphenol (NP), on target tissue sensitivity to insulin-like growth factor (IGF) as assessed by expression of IGF receptor type 1 (IGFR1) mRNAs and IGF-1 binding capacity, as well as on the cell signaling pathways through which EE exert their effects. E2 and NP inhibited IGFR1A and IGFR1B mRNA expression in a time- and concentration-related manner in gill and muscle; however, βS had no effect on expression of IGFR1 mRNAs in either tissue. NP reduced 125I-IGF binding in gill and E2 and NP reduced 125I-IGF in white muscle; βS had no effect on 125I-IGF binding in either gill or white muscle. Treatment of gill filaments with either E2 or NP rapidly deactivated (via reduced proportion of phosphorylation) JAK2, STAT5, Akt, and ERK; βS had no effect on the activation state of any cell signaling elements tested. The effects of EE on IGFR mRNA expression in gill were estrogen receptor (ER) dependent as the inhibitory effects were rescued by the ER antagonist, ICI 182,780. All EE tested blocked growth hormone (GH)-stimulated IGFR mRNA expression in gill filaments. GH-stimulated activation of JAK2, STAT5, Akt, and ERK were blocked by E2, βS, and NP. Lastly, E2 and NP stimulated suppressor of cytokine signaling 2 (SOCS-2) mRNA expression, an effect that also was ER dependent. These results indicate that EE directly reduce the sensitivity of peripheral tissues to IGF by reducing mRNA and functional expression of IGFRs. Such inhibitory actions of EE are mediated, at least in part, by ER-dependent mechanisms that deactivate JAK, STAT, Akt, and ERK and enhance expression of SOCS-2. These findings together with our previous results show that EE retard growth of post-embryonic rainbow trout through widespread direct effects on the GH-IGF system, specifically, by reducing tissue sensitivity to GH, inhibiting IGF production, reducing tissue sensitivity to IGF, and by deactivating post-receptor IGF cell signaling pathways.

Investigation of free and conjugated estrogen fate and emission coefficients in three duck farms.

Concentration animal feeding operation (CAFO) is an important source of environmental estrogen. However, to the best of our knowledge, the data on estrogen discharge during duck breeding and growth is insufficient. This study used liquid chromatography with tandem mass spectrometry (LC/MS/MS) to analyze the free and conjugated estrogen concentrations in the surface water, outlet water, groundwater, and duck manure/soil mixture at three duck farms in Taiwan. Natural estrogen species included estrone (E1), 17β-estradiol (E2), estriol (E3), estrone-3-sulfate (E1-3S), 17β-estradiol-3-sulfate (E2-3S), estrone-3-glucuronide (E1-3G), and 17β-estradiol-3-glucuronide (E2-3G), whereas synthetic estrogen included 17α-ethynylestradiol (EE2) and diethylstilbestrol (DES). This study showed that the total estrogen concentrations in the surface water and groundwater were 15.4 and 4.5ng/L, respectively, which constituted 56% and 58%, respectively, conjugated estrogen. From the pond to the outlet water, the total estrogen concentration decreased by 3.9ng/L (23% loss) in the duck farms. However, the estrogenic potency was slightly reduced from 0.91 to 0.88 E2 equivalent/L, showing a negligible decrease. From the pond to the outlet water, the field results showed that converting the conjugated estrogen into free estrogen in the duck farm-released water increased their environmental hazard. Primarily E1, with an average concentration of 0.9 ± 1.6ng/g, was present in the duck manure. The estrogen excreted by the ducks in the pond (from surface water to outlet water) was estimated to be 0.18kg/million head-year. Although the estrogen concentration in the duck farms was low, the environmental impact of CAFO should not be neglected.

Dual-Mechanism Quenching of Electrochemiluminescence Immunosensor Based on a Novel ECL Emitter Polyoxomolybdate-Zirconia for 17β-Estradiol Detection.

The exploration of novel electrochemiluminescence (ECL) reagents has been a breakthrough work in ECL immunoassay. In this work, the ECL properties of polyoxomolybdate-zirconia (POM-ZrO2) were discovered for the first time and their luminescence mechanism was initially explored. Virgulate POM-ZrO2 was synthesized from phosphomolybdic acid hydrate and zirconium oxychloride by solvothermal method, which achieved intense and stabilized cathode ECL emission at a negative potential. Polyaniline@Au nanocrystals (PANI@AuNPs) as the executor of the dual-mechanism quenching strategy were used to reduce the output signal. The quenching efficiency was significantly enhanced by the dual mechanisms of ECL energy transfer and electron transfer. Specifically, PANI@AuNPs can serve as an energy receptor to absorb the energy emitted by POM-ZrO2 (energy donor), while the appropriate energy level can be regarded as the condition for electron transfer to quench the ECL intensity of POM-ZrO2. Herein, the proposed dual-mechanism quenching strategy was applied to the immunoassay of 17β-estradiol by constructing a competitive immunosensor. As expected, the immunosensor demonstrated favorable analytical performance and a wide sensing range from 0.01 pg/mL to 200 ng/mL. Hence, it provides a novel method for the sensitive analysis of other biomolecules, such as disease markers and environmental estrogens.

P12-14 Adaptation of the E-Morph Assay to serum-free cell culture conditions for CellPainting-based phenotypic screening of environmental estrogens

P12-14 Adaptation of the E-Morph Assay to serum-free cell culture conditions for CellPainting-based phenotypic screening of environmental estrogens

Lysinibacillus sp. GG242 from Cattle Slurries Degrades 17β-Estradiol and Possible 2 Transformation Routes.

Environmental estrogen pollution has long been a concern due to adverse effects on organisms and ecosystems. Biodegradation is a vital way to remove estrogen, a strain of Lysinibacillus sp. was isolated, numbered strain GG242. The degradation rate of 100 mg·L−1 17β-estradiol (E2)) > 95% in one week, and compared with extracellular enzymes, intracellular enzymes have stronger degradation ability. Strain GG242 can maintain a stable E2 degradation ability under different conditions (20–35 °C, pH 5–11, salinity 0–40 g·L−1). Under appropriate conditions (30 °C, pH 8, 1 g·L−1 NaCl), the degradation rate increased by 32.32% in one week. Based on the analysis of transformation products, inferred E2 was converted via two distinct routes. Together, this research indicates the degradation potential of strain GG242 and provides new insights into the biotransformation of E2.

Highly sensitive and group-targeting detection of steroid estrogens in water environment using a valid oligonucleotide class-specific editing technique

Steroid environmental estrogens (SEEs) are often coexist in water, require complex analytical techniques for separation and monitoring. However, aptamer-based chemical detection often only recognizes one of them, and the detection of SEEs is still a huge challenge. Herein, a group-targeting aptamer with the ability to recognize SEEs was constructed using efficient oligonucleotide class-specific editing technology, and a photoelectrochemical aptasensor capable of detecting the class of SEEs was established. A quantitative analysis of highly toxic SEEs in the environment and carrying similar core carbon skeleton, including 17β-estradiol, esterone, estriol and ethinylestradiol, was performed. The detection limit was as low as 0.1 nM with a response time of only 15 min. Specifically, this method exhibited high anti-interference with different complex media existing. Combining the theoretical calculations with a variety of spectral experiments, the Π-Π stacking and hydrogen bond synergistic interactions between the photoelectric interface and the three ring structures on SEEs and the hydroxyl group of ring 1 were analyzed in depth. Besides, the conformational changes of loose base helix structure and the free rotation limitation of oligonucleotides after the recognition of SEEs at the molecular level were also elucidated, facilitating the transfer of electrons on the surface of the photoelectrode.

Environmental Enrichment and Estrogen Upregulate Beta-Hydroxybutyrate Underlying Functional Improvement.

Environmental enrichment (EE) is a promising therapeutic strategy in improving metabolic and neuronal responses, especially due to its non-invasive nature. However, the exact mechanism underlying the sex-differential effects remains unclear. The aim of the current study was to investigate the effects of EE on metabolism, body composition, and behavioral phenotype based on sex. Long-term exposure to EE for 8 weeks induced metabolic changes and fat reduction. In response to the change in metabolism, the level of βHB were influenced by sex and EE possibly in accordance to the phases of estrogen cycle. The expression of β-hydroxybutyrate (βHB)-related genes and proteins such as monocarboxylate transporters, histone deacetylases (HDAC), and brain-derived neurotrophic factor (BDNF) were significantly regulated. In cerebral cortex and hippocampus, EE resulted in a significant increase in the level of βHB and a significant reduction in HDAC, consequently enhancing BDNF expression. Moreover, EE exerted significant effects on motor and cognitive behaviors, indicating a significant functional improvement in female mice under the condition that asserts the influence of estrogen cycle. Using an ovariectomized mice model, the effects of EE and estrogen treatment proved the hypothesis that EE upregulates β-hydroxybutyrate and BDNF underlying functional improvement in female mice. The above findings demonstrate that long-term exposure to EE can possibly alter metabolism by increasing the level of βHB, regulate the expression of βHB-related proteins, and improve behavioral function as reflected by motor and cognitive presentation following the changes in estrogen level. This finding may lead to a marked improvement in metabolism and neuroplasticity by EE and estrogen level.

Preparation of Graphene Quantum Dots by Visible-Fenton Reaction and Ultrasensitive Label-Free Immunosensor for Detecting Lipovitellin of Paralichthys Olivaceus.

The increasing levels of environmental estrogens are causing negative effects on water, soil, wildlife, and human beings; label-free immunosensors with high specificities and sensitivities are being developed to test estrogeneous chemicals in complex environmental conditions. For the first time, highly fluorescent graphene quantum dots (GQDs) were prepared using a visible-Fenton catalysis reaction with graphene oxide (GO) as a precursor. Different microscopy and spectroscopy techniques were employed to characterize the physical and chemical properties of the GQDs. Based on the fluorescence resonance energy transfer (FRET) between amino-functionalized GQDs conjugated with anti-lipovitellin monoclonal antibodies (Anti-Lv-mAb) and reduced graphene oxide (rGO), an ultrasensitive fluorescent “ON-OFF” label-free immunosensor for the detection of lipovitellin (Lv), a sensitive biomarker derived from Paralichthys olivaceus for environmental estrogen, has been established. The immunosensor has a wide linear test range (0.001–1500 ng/mL), a lower limit of detection (LOD, 0.9 pg/mL), excellent sensitivity (26,407.8 CPS/(ng/mL)), and high selectivity and reproducibility for Lv quantification. The results demonstrated that the visible-Fenton is a simple, mild, green, efficient, and general approach to fabricating GQDs, and the fluorescent “ON-OFF” immunosensor is an easy-to-use, time-saving, ultrasensitive, and accurate detection method for weak estrogenic activity.

Bisphenol A Interferes with Redox Balance and the Nrf2 Signaling Pathway in Xenopus tropicalis during Embryonic Development.

Simple SummaryToxicological studies of the effects of BPA on tropical clawed frog (Xenopus tropicalis) early embryos show that temporary exposure to BPA during early embryonic development can result in dramatic teratogenesis, DNA damage, and abnormal gene expression. The overall results of this study provide valuable insights for a more holistic assessment of the environmental risks related to BPA in aquatic ecosystems.Bisphenol A (BPA), an environmental estrogen, is widely used and largely released into the hydrosphere, thus inducing adverse effects in aquatic organisms. Here, Xenopus tropicalis was used as an animal model to investigate the oxidative effects of BPA on early embryonic development. BPA exposure prevalently caused development delay and shortened body length. Furthermore, BPA exposure significantly increased the levels of reactive oxygen species (ROS) and DNA damage in embryos. Thus, the details of BPA interference with antioxidant regulatory pathways during frog early embryonic development should be further explored.

Waves of follicle development, growth and degeneration in adult ovary of zebrafish (Danio rerio) on chronic exposure to environmental estrogens in laboratory

Patterns of quantitative production of follicles, their growth, and degeneration in the adult ovary of zebrafish (Danio rerio) in response to long-term (80 days) exposure to environmental estrogens (EE) in the laboratory, were studied. Experimentally naive female D. rerio procured from fish farm were acclimated to the laboratory (natural temperature, 26 ± 1° C, photoperiod, 11.30 L:12.30 D) for two weeks and divided into 10 groups. Each group (n = 20) was housed in a separate glass aquarium containing 10 L of conditioned water (physico-chemical parameters maintained within the permissible range prescribed for zebrafish) along with either 5 ng or 10 ng/L of 17α-ethynylestradiol (EE2) or diethylstilbestrol (DES) or bisphenol A (BPA) or estradiol 17-β (positive control) or water with no chemical (negative control). All experimental fish were fed twice daily on commercial pellets (ad libitum) supplemented with Artemia nauplius, the exposure was semi-static and chemical residues in media samples were determined by ultra-performance liquid chromatography (UPLC). Exposure of fish to estrogens increased (p < 0.05) (i) body mass and gonadosomatic indices (GSI) in E2, EE2 and DES groups (ii) previtellogenic and vitellogenic follicles in E2 and EE2 groups (iii) atretic follicles (AF) in DES and BPA groups compared to controls and (iv) decrease in total oocyte volumes (V = 4/3. π. r3) compared to those of E2 group. These results suggest that the chronic exposure of fish to EE (at environmentally relevant concentrations) has a profound influence on ovarian follicular dynamics and the effects of individual EE are discrete on the ovary.

Diethylhexyl Phthalate and Bisphenol A Promote Vincristine and Tamoxifen Resistance in Vitro.

Environmental estrogen active compounds are strong determinants of estrogen receptor (ER)-positive breast cancers, and increased evidence indicates their contribution to chemotherapy resistance. In the current study, the efficacy of vincristine and tamoxifen, with the presence of diethylhexyl phthalate (DEHP) and bisphenol A (BPA) and the possible involvement of estrogen and estrogen receptor-related mechanisms, was evaluated in an ER+ mammary tumor cancer cell line, MCF-7. Chemotherapeutics tamoxifen as an estrogen receptor modulator and vincristine as an antimitotic compound were selected for evaluation against the presence of common endocrine disrupters. BPA and DEHP preincubation at their proliferative concentrations for 4 h was found to decrease the cytotoxicity of vincristine. mRNA and protein expression of ESR1 and ESR 2 were decreased by vincristine, while this decrease was reversed by DEHP and BPA. Both BPA and DEHP were able to interfere with the cytotoxic activity of vincristine against MCF-7 cells through ESR1 and ESR2. This study provides in vitro toxicological evidence for vincristine resistance and its relation to estrogen active environmental pollutants in ER+ breast cancer cells.

Recent Advances on Innovative Materials from Biowaste Recycling for the Removal of Environmental Estrogens from Water and Soil.

New technologies have been developed around the world to tackle current emergencies such as biowaste recycling, renewable energy production and reduction of environmental pollution. The thermochemical and biological conversions of waste biomass for bioenergy production release solid coproducts and byproducts, namely biochar (BC), hydrochar (HC) and digestate (DG), which can have important environmental and agricultural applications. Due to their physicochemical properties, these carbon-rich materials can behave as biosorbents of contaminants and be used for both wastewater treatment and soil remediation, representing a valid alternative to more expensive products and sophisticated strategies. The alkylphenols bisphenol A, octylphenol and nonylphenol possess estrogenic activity comparable to that of the human steroid hormones estrone, 17β-estradiol (and synthetic analog 17α-ethinyl estradiol) and estriol. Their ubiquitous presence in ecosystems poses a serious threat to wildlife and humans. Conventional wastewater treatment plants often fail to remove environmental estrogens (EEs). This review aims to focus attention on the urgent need to limit the presence of EEs in the environment through a modern and sustainable approach based on the use of recycled biowaste. Materials such as BC, HC and DG, the last being examined here for the first time as a biosorbent, appear appropriate for the removal of EEs both for their negligible cost and continuously improving performance and because their production contributes to solving other emergencies, such as virtuous management of organic waste, carbon sequestration, bioenergy production and implementation of the circular economy. Characterization of biosorbents, qualitative and quantitative aspects of the adsorption/desorption process and data modeling are examined.

Do microplastics impair male dominance interactions in fish? A test of the vector hypothesis.

Microplastics (MPs) are widespread in aquatic environments and have become a critical environmental issue in recent years due to their adverse impacts on the physiology, reproduction, and survival of aquatic animals. Exposure to MPs also has the potential to induce sub‐lethal behavioral changes that can affect individual fitness, but these effects are understudied. Many plastic additives introduced during the manufacture of MPs are known endocrine‐disrupting chemicals (EDCs) that mimic the action of natural hormones, alter sexual and competitive behavior, and impair reproductive success in fish. In addition, EDCs and other aquatic contaminants may adhere to MPs in the environment, the latter of which may serve as transport vectors for these compounds (i.e., the vector hypothesis). In this study, we staged territorial contests between control males, and males exposed to virgin MP particles or to MPs previously immersed in one of two environmentally relevant concentrations of 17‐alpha ethinyl estradiol (EE2; 5 ng/L and 25 ng/L) to evaluate the independent and synergistic effects of exposure to MPs and a common environmental estrogen on male–male aggression and competitive territory acquisition in a freshwater fish, Pimephales promelas. Short‐term (30 days) dietary exposure to MPs did not impair the ability of males to successfully compete for and obtain a breeding territory. Overall levels of aggression in control and exposed males were also similar across trial series. These results help to fill a critical knowledge gap regarding the direct and indirect (vector‐borne) effects of MPs on the reproductive behavior of aquatic vertebrates in freshwater systems.