Exploring the interplay between bisphenol A exposure, the immune microenvironment and hepatocellular carcinoma progression.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a formidable challenge in oncology, with its pathogenesis and progression influenced by myriad factors. Among them, the pervasive organic synthetic compound, bisphenol A (BPA), previously linked with various adverse health effects, has been speculated to play a role. This study endeavors to elucidate the complex interplay between BPA, the immune microenvironment of HCC, and the broader molecular landscape of this malignancy. METHODS: A comprehensive analysis was undertaken using data procured from both The Cancer Genome Atlas and the Comparative Toxicogenomics Database. Rigorous differential expression analyses were executed, supplemented by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. In addition, single-sample gene set enrichment analysis, gene set enrichment analysis and gene set variation analysis were employed to reveal potential molecular links and insights. Immune infiltration patterns were delineated, and a series of in vitro experiments on HCC cells were conducted to directly assess the impact of BPA exposure. RESULTS: Our findings unveiled a diverse array of active immune cells and functions within HCC. Distinct correlations emerged between high-immune-related scores, established markers of the tumor microenvironment and the expression of immune checkpoint genes. A significant discovery was the identification of key genes simultaneously associated with immune-related pathways and BPA exposure. Leveraging these genes, a prognostic model was crafted, offering predictive insights into HCC patient outcomes. Intriguingly, in vitro studies suggested that BPA exposure could promote proliferation in HCC cells. CONCLUSION: This research underscores the multifaceted nature of HCC's immune microenvironment and sheds light on BPA's potential modulatory effects therein. The constructed prognostic model, if validated further, could serve as a robust tool for risk stratification in HCC, potentially guiding therapeutic strategies. Furthermore, the implications of the findings for immunotherapy are profound, suggesting new avenues for enhancing treatment efficacy. As the battle against HCC continues, understanding of environmental modulators like BPA becomes increasingly pivotal.

Unveiling the potential of estrogen: Exploring its role in neuropsychiatric disorders and exercise intervention.

Neuropsychiatric disorders shorten human life spans through multiple ways and become major threats to human health. Exercise can regulate the estrogen signaling, which may be involved in depression, Alzheimer's disease (AD) and Parkinson's disease (PD), and other neuropsychiatric disorders as well in their sex differences. In nervous system, estrogen is an important regulator of cell development, synaptic development, and brain connectivity. Therefore, this review aimed to investigate the potential of estrogen system in the exercise intervention of neuropsychiatric disorders to better understand the exercise in neuropsychiatric disorders and its sex specific. Exercise can exert a protective effect in neuropsychiatric disorders through regulating the expression of estrogen and estrogen receptors, which are involved in neuroprotection, neurodevelopment, and neuronal glucose homeostasis. These processes are mediated by the downstream factors of estrogen signaling, including N-myc downstream regulatory gene 2 (Ndrg2), serotonin (5-HT), delta like canonical Notch ligand 1 (DLL1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), etc. In addition, exercise can act on the estrogen response element (ERE) fragment in the genes of estrogenic downstream factors like ß-amyloid precursor protein cleavase 1 (BACE1). However, there are few studies on the relationship between exercise, the estrogen signaling pathway, and neuropsychiatric disorders. Hence, we review how the estrogen signaling mediates the mechanism of exercise intervention in neuropsychiatric disorders. We aim to provide a theoretical perspective for neuropsychiatric disorders affecting female health and provide theoretical support for the design of exercise prescriptions.

Urinary concentrations of bisphenol A and its alternatives: Potential predictors of and associations with antral follicle count among women from an infertility clinic in Northern China.

BACKGROUND: Experimental studies have suggested exposure to bisphenol A (BPA) and its alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), may exert adverse effects on ovarian reserve, but human evidence is limited. Moreover, the potential predictors of exposure to bisphenols among women seeking infertility treatment have not been reported. OBJECTIVE: To explore whether individual or mixture of BPA, BPF, and BPS were related to antral follicle count (AFC), and further identify the predictors of exposure to bisphenols among women seeking assisted reproductive treatment. METHODS: A total of 111 women from a reproductive center in Shenyang, China were enrolled in this study from September 2020 to February 2021. The concentrations of urinary BPA, BPF, and BPS were measured using ultra-high-performance liquid chromatography-triple quadruple mass spectrometry (UHPLC-MS/MS). AFC was measured by two infertility physicians through transvaginal ultrasonography on the 2-5 days of a natural cycle. Demographic characteristics, dietary habits, and lifestyles were obtained by questionnaires. The associations between individual and mixture of urinary bisphenols concentrations (BPA, BPF, and BPS) and AFC were assessed by the Poisson regression models and the quantile-based g-computation (QGC) model, respectively. The potential predictors of exposure to bisphenols were identified by the multivariate linear regression models. RESULTS: After adjusting for confounders, elevated urinary concentrations of BPA, BPF and BPS were associated with reduced AFC (ß = -0.016; 95%CI: -0.025, -0.006 in BPA; ß = -0.017; 95%CI: -0.029, -0.004 in BPF; ß = -0.128; 95%CI: -0.197, -0.060 in BPS). A quantile increase in the bisphenols mixture was negatively associated with AFC (ß = -0.101; 95%CI: -0.173, -0.030). Intake of fried food had higher urinary concentrations of BPF, BPS, and total bisphenols (∑BPs) than women who did not eat, and age was related to increased urinary BPF concentrations. CONCLUSION: Our findings indicated that exposure to individual BPA, BPF, BPS and bisphenol mixtures were associated with impaired ovarian reserve. Furthermore, the intake of fried food, as identified in this study, could serve as an important bisphenols exposure route for reproductive-aged women.

Exposure to bisphenol A affects transcriptome-wide N6-methyladenine methylation in ovarian granulosa cells.

Bisphenol A (BPA) is an endocrine disruptor of potential reproductive toxicities. Increasingly research elucidated that BPA exposure to the environment would change the epigenetic modifications of transcriptome, but the mechanism by which BPA affects m6A methylation in interfering with female reproductive health remains uncertain. Therefore, this study preliminarily proposed and tested the hypothesis that BPA exposure alters the m6A modification level in transcripts in female ovarian granulosa cells. After BPA was exposed to granulosa cells for 24 h, RNA methylation related regulatory genes (such as METTL3, METTL14, ALKBH5, FTO) and the global m6A levels showed significant differences. Next, we applied MERIP-seq analysis to obtain information on the genome-wide m6A modification changes and identified 1595 differentially methylated mRNA transcripts, and 50 differentially methylated lncRNA transcripts. Further joint analysis of gene common expression showed that 33 genes were hypermethylated and up-regulated, 71 were hypermethylated and down-regulated, 49 were hypomethylated and up-regulated, and 20 were hypomethylated and down-regulated. Enriched Gene Ontology (GO) and biological pathway analysis revealed that these unique genes were mainly enriched in lipid metabolism, cell proliferation, and apoptosis related pathways. Six of these genes (mRNAs IMPA1, MCOLN1, DCTN3, BRCA2, and lncRNAs MALAT1, XIST) were validated using RT-qPCR and IGV software. Through comprehensive analysis of epitranscriptome and protein-protein interaction (PPI) data, lncRNAs MALAT1 and XIST are expected to serve as new markers for BPA interfering with the female reproductive system. In brief, these data show a novel and necessary connection between the damage of BPA exposure on female ovarian granulosa cells and RNA methylation modification.

Application of the Key Characteristics of Carcinogens to Bisphenol A.

The ten key characteristics (KCs) of carcinogens are based on characteristics of known human carcinogens and encompass many types of endpoints. We propose that an objective review of the large amount of cancer mechanistic evidence for the chemical bisphenol A (BPA) can be achieved through use of these KCs. A search on metabolic and mechanistic data relevant to the carcinogenicity of BPA was conducted and web-based software tools were used to screen and organize the results. We applied the KCs to systematically identify, organize, and summarize mechanistic information for BPA, and to bring relevant carcinogenic mechanisms into focus. For some KCs with very large data sets, we utilized reviews focused on specific endpoints. Over 3000 studies for BPA from various data streams (exposed humans, animals, in vitro and cell-free systems) were identified. Mechanistic data relevant to each of the ten KCs were identified, with receptor-mediated effects, epigenetic alterations, oxidative stress, and cell proliferation being especially data rich. Reactive and bioactive metabolites are also associated with a number of KCs. This review demonstrates how the KCs can be applied to evaluate mechanistic data, especially for data-rich chemicals. While individual entities may have different approaches for the incorporation of mechanistic data in cancer hazard identification, the KCs provide a practical framework for conducting an objective examination of the available mechanistic data without a priori assumptions on mode of action. This analysis of the mechanistic data available for BPA suggests multiple and inter-connected mechanisms through which this chemical can act.

Bisphenol A: Unveiling Its Role in Glioma Progression and Tumor Growth.

Gliomas represent the most common and lethal category of primary brain tumors. Bisphenol A (BPA), a widely recognized endocrine disruptor, has been implicated in the progression of cancer. Despite its established links to various cancers, the association between BPA and glioma progression remains to be clearly defined. This study aimed to shed light on the impact of BPA on glioma cell proliferation and overall tumor progression. Our results demonstrate that BPA significantly accelerates glioma cell proliferation in a time- and dose-dependent manner. Furthermore, BPA has been found to enhance the invasive and migratory capabilities of glioma cells, potentially promoting epithelial-mesenchymal transition (EMT) characteristics within these tumors. Employing bioinformatics approaches, we devised a risk assessment model to gauge the potential glioma hazards associated with BPA exposure. Our comprehensive analysis revealed that BPA not only facilitates glioma invasion and migration but also inhibits apoptotic processes. In summary, our study offers valuable insights into the mechanisms by which BPA may promote tumorigenesis in gliomas, contributing to the understanding of its broader implications in oncology.

Screening bisphenols in complex samples via a planar Arxula adeninivorans bioluminescence bioassay.

The Arxula yeast bisphenol screen (A-YBS) utilizes the bioluminescent Arxula adeninivorans yeast-based reporter cells for tailored analysis of bisphenols, one of the major endocrine-disrupting compound groups. For the first time, this bioreporter has been applied on the high-performance thin-layer chromatography (HPTLC) adsorbent surface to develop a respective planar bioluminescence bioassay (pA-YBS). The goal was to combine the advantages of HPTLC with a more selective bioassay detection for bisphenols. The performance of this pA-YBS bioluminescence bioassay was demonstrated by calculating the half-maximal effective concentration (EC50) of bisphenols compared to references. The EC50 ranged from 267 pg/band for bisphenol Z and 322 pg/band for bisphenol A (BPA) to > 1 ng/band for other bisphenols (BPC, BPE, BPF, and BPS) and references (17ß-estradiol and 17α-ethinylestradiol). The EC50 value of BPA was three times more sensitive in signal detection than that of 17ß-estradiol. The visual or videodensitometric limit of detection of BPA was about 200 pg/zone. The higher signal intensity and sensitivity for BPA confirmed the tailored bioassay selectivity compared to the existing estrogen screen bioassay. It worked on different types of HPTLC silica gel plates. This HPTLC-UV/Vis/FLD-pA-YBS bioluminescence bioassay method was used to analyze complex mixtures such as six tin can migrates, five thermal papers, and eleven botanicals. The detected estrogenic compound zones in the tin can migrates were successfully verified via the duplex planar yeast antagonist estrogen screen (pYAES) bioassay. The two bisphenols A and S were identified in one out of five thermal papers and confirmed with high-resolution mass spectrometry. No bisphenols were detected in the botanicals investigated via the pA-YBS bioluminescence bioassay. However, the botanicals proved to contain phytoestrogens as detected via the pYAES bioassay, which confirmed the tailored bioassay selectivity. This HPTLC-UV/Vis/FLD-pA-YBS bioluminescence bioassay is suited for cost-efficient analysis of BPA in complex samples, with no need for sterile conditions due to the fast workflow.

Phthalates, adipates, BPA, and pesticides in school meals.

BACKGROUND: Exposure to phthalates, adipates, bisphenol-A (BPA), and pesticides may have important health consequences for children, but little is known regarding their presence in school meals, a major food source for children. The aims of this study were to determine the presence of phthalates, adipates, BPA, and pesticides in school meals. METHODS: Using a cross-sectional design, n = 50 school meal components were collected from four school districts in New England (n = 8 elementary/K-8 schools) differing preparation methods (on-site scratch cooking and pre-packaged heat and serve meals with plastic films) between 2019 and 2021. Meal components were tested for the presence of phthalates, adipates, BPA, and pesticides by an independent laboratory. RESULTS: One adipate, DEHA, was detected in 42% of samples (range 0.08 mg/kg - 50.39 mg/kg). Among the prepackaged foods, DEHA was detected in 86% of samples, which also contained the highest average concentrations among all the samples tested. The phthalate Diisononyl phthalate (DINP) was detected in only one sample, and BPA was not detected in any of the samples tested. Pesticides were detected in 64% of produce and 27% of entrées, but most had levels that were lower than the average levels detected by the USDA's Pesticide Data Program and only one sample had levels that exceeded those detected by the USDA (Cyfluthrin levels in one sample of apples were 0.038 mg/kg compared with an USDA average range of 0.004-0.032 mg/kg). CONCLUSIONS: Overall pesticides and phthalate levels in school meals are low and BPA was not detected. However, this study suggests that manufacturers may be changing to less studied plasticizers such as DEHA. More studies should examine the impact of DEHA on human health, particularly among children. As schools transition back from the COVID-19 pandemic, foods packaged in plastic should be minimized where possible. Overall, school meals remain one of the healthiest options for children and policies that support on site cooking can further strengthen the quality of school meals.

Human health risk assessment for consumption of microplastics and plasticizing substances through marine species.

A special characteristic of MP (microplastics) in the ocean is they may act as carriers of additives specific to the plastic materials used in their manufacture, such as plasticizers, among which Bisphenol-A (BPA), bis (2-ethylhexyl) phthalate (DEHP), dybuthyl phthalate (DBP). Both MP as the plasticizers were searched in composite samples of mangrove cockle (Anadara tuberculosa), Stolzmann's weakfish (Cynoscion stolzmanni) and arched swimming crab (Callinectes arcuatus). Extraction of MP was done through physical-chemical techniques and identification was carried out employing the techniques of light microscopy, energy dispersive spectrometer (EDS), scanning electron microscope (SEM) and Raman spectroscopy; the sizes of MP obtained were between 0.5 µm and 106 µm, the following average results being obtained: for Arched swimming crab 4.0 ± 1.0 MP/g; mangrove cockle 3.3 ± 2.9 MP/g; and for Stolzmann's weakfish, the average was 2.4 ± 1.3 MP/g; the most observed shapes were fibers and irregular segments; the most identified MP was polyethylene terephthalate (PET). Regarding extraction and quantification of plasticizers, the extraction stage was carried out using QuEChERS tubes; and the identification and quantification with gas chromatography coupled to a mass spectrometer (GC-MS). Regarding the plasticizing substances, DEHP was found in detectable levels in all the samples; BPA was found in 84% of the composite samples analyzed; DBP was found in 50% of them, of the analyzed samples 34% were positive for the 3 analytes. The dietary exposure of people to plasticizers was calculated and for BPA the exposure obtained was compared with respect to the TDI (tolerable intake dose) for pregnant women and the new TDI proposed by EFSA in 2021 according to the estrogenic effect of this substance in the fetus. The objective of the work was to determine if a relationship could be established between both PM and plasticizers, which gave a positive relationship.

Efficient adsorption of organic pollutants phthalates and bisphenol A (BPA) utilizing magnetite functionalized covalent organic frameworks (MCOFs): A promising future material for industrial applications.

The utilization of phthalates and bisphenol A (BPA) as the major component in plastic and its derivative industry has raised concerns among the public due to the harmful effects caused by these organic pollutants. These pollutants are found to exhibit unique physicochemical properties that allow the pollutants to have prolonged existence in the environment, thus causing damage to the environment. Since phthalates and bisphenol A are used in a variety of industrial applications, the industry must recover these compounds from its water before releasing the pollutants into the environment. As a result, these materials have a promising future in industrial applications. Therefore, the discovery of new quick and reliable abatement technologies is important to ensure that these organic pollutants can be detected and removed from the water sources. This review highlights the use of the adsorption method to remove phthalates and BPA from water sources by employing novel modified adsorbent magnetite functionalized covalent organic frameworks (MCOFs). MCOFs is a new class of porous materials that have demonstrated promising features in a variety of applications due to their adaptable structures, significant surface areas, configurable porosity, and customizable chemistry. The structural attributes, functional design strategies, and specialized for environmental applications before offering some closing thoughts and suggestions for further research were discussed in this paper in addition to developing an innovative solution for the industry to the accessibility for clean water.

Dysfunction of the medial prefrontal cortex contributes to BPA-induced depression- and anxiety-like behavior in mice.

Bisphenol A (BPA), a well-known environmental endocrine disruptor, has been implicated in anxiety-like behavior. But the neural mechanism remains elusive. Herein, we found that mice exposed to 0.5 mg/kg/day BPA chronically from postnatal days (PND) 21 to PND 80 exhibited depression- and anxiety-like behavior. Further study showed that medial prefrontal cortex (mPFC), was associated with BPA-induced depression- and anxiety-like behavior, as evidenced by decreased c-fos expression in mPFC of BPA-exposed mice. Both the morphology and function of glutamatergic neurons (also called pyramidal neurons) in mPFC of mice were impaired following BPA exposure, characterized by reduced primary branches, weakened calcium signal, and decreased mEPSC frequency. Importantly, optogenetic activation of the pyramidal neurons in mPFC greatly reversed BPA-induced depression- and anxiety-like behavior in mice. Furthermore, we reported that microglial activation in mPFC of mice may also have a role in BPA-induced depression- and anxiety-like behavior. Taken together, the results indicated that mPFC is the brain region that is greatly damaged by BPA exposure and is associated with BPA-induced depression- and anxiety-like behavior. The study thus provides new insights into BPA-induced neurotoxicity and behavioral changes.

The association between maternal urinary Bisphenol A levels and neurodevelopment at age 2 years in Chinese boys and girls: A prospective cohort study.

The impact of maternal exposure to Bisphenol A on child cognitive development as well as its sex dimorphism remains uncertain. This study used data of 215 mothers and their children from a birth cohort in Shanghai. Urinary BPA were measured in spot urine samples of mothers at late pregnancy and children at age 2 years. Cognitive development was evaluated by Ages & Stages Questionnaires, Third Edition (ASQ-3) at age 2 years. Urinary BPA was detectable in 98.9% of mothers (geometric mean, GM: 2.6 µg/g. creatinine) and 99.8% children (GM: 3.4 µg/g. creatinine). Relative to the low and medium BPA tertiles, high tertile of maternal urinary BPA concentrations were associated with 4.8 points lower (95% CI: -8.3, -1.2) in gross motor and 3.7 points lower (95% CI: -7.4, -0.1) in problem-solving domain in girls only, with adjustment for maternal age, maternal education, pre-pregnancy BMI, passive smoking during pregnancy, parity, delivery mode, birth-weight for gestational age, child age at ASQ-3 test. This negative association remained with additional adjustment for child urinary BPA concentrations at age 2 years. No association was observed in boys. These results suggested the sex-dimorphism on the associations of maternal BPA exposure with gross motor and problem-solving domains in children at age 2 years. This study also indicated that optimal early child development should start with a healthy BPA-free "in utero" environment.

In utero bisphenol A exposure disturbs germ cell cyst breakdown through the PI3k/Akt signaling pathway and BDNF expression.

PURPOSE: To determine the influence of the environmental endocrine disruptor bisphenol A (BPA) on germ cell cyst breakdown and explore the possible mechanisms regulating this activity. METHODS: BPA (2 µg/kg/d or 20 µg/kg/d) or tocopherol-stripped corn oil (vehicle control) was administered to pregnant mice by gavage at gestational day 11, and the offspring (prenatally treated mice) were sacrificed and ovariectomized at postnatal day (PND) 4 and PND22. Ovarian morphology was documented in the first filial (F1) generation female offspring, and the follicles were analyzed and classified morphologically on PND 4. To discover differentially expressed genes and associated target pathways, we used RNA-seq, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Ontology (GO) analysis. The mRNA expression of key steroid hormone synthesis-related genes was evaluated by Q-PCR in forskolin-induced KGN cells. Western blotting (WB) and qRTPCR were used to determine the protein and gene expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: BPA, a typical endocrine disrupting chemical (EDC), decreased the expression of the key steroid hormone synthesis-related genes P450scc and aromatase, while the expression of Star increased significantly and caused no significant difference in the expression of Cyp17a1 or HSD3ß in forskolin-induced KGN cells. Moreover, we confirmed that in utero exposure to environmentally relevant concentrations of BPA (2 µg/kg/d and 20 µg/kg/d) could significantly disrupt germ cell cyst breakdown, leading to the generation of fewer primordial follicles than in the control group. The factors mediating the inhibitory effects included the PI3K-Akt signaling pathway and a significant downregulation of BDNF. CONCLUSIONS: These findings indicate that in utero exposure to BPA at low doses, which are lower than recommended as 'safe' dosages, may influence the formation of primordial follicles by inhibiting the expression of steroid hormone synthesis-related genes and partly by regulating the BDNF-mediated PI3K/Akt pathway.

The Association between the Bisphenols Residues in Amniotic Fluid and Fetal Abnormalities in Polish Pregnant Women-Its Potential Clinical Application.

The present study aimed to investigate the relationship between the concentrations of bisphenols residues in the amniotic fluid (AF) samples collected during amniocentesis and fetal chromosomal abnormalities in pregnant women. A total of 33 pregnant Polish women aged between 24 and 44 years, and screened to detect high risk for chromosomal defects in the first trimester, were included in this study. Samples were collected from these patients during routine diagnostic and treatment procedures at mid-gestation. The concentrations of various bisphenols residues in the samples were determined by liquid chromatography coupled with triple quadrupole tandem mass spectrometry (LC-ESI-QqQ-MS/MS). Residues of eight analytes (BPS, BPF, BPA, BPAF, BADGE, BADGE•2H2O, BADGE•H2O•HCl and BADGE•2HCl) were detected in amniotic fluid samples in the range 0.69 ng/mL to 3.38 ng/mL. Fetuses with chromosomal abnormalities showed a slightly higher frequency of occurrence of selected bisphenols residues in the AF samples collected between 15-26 weeks of pregnancies. Finally, the proposed method was applied in the simultaneous determination of several endocrine-disrupting chemicals from bisphenol group in 33 human AF samples. BADGE•H2O•HCl has been identified in the AF samples taken from women older than average in the examined group. The number of detected compounds has been significant for the following analytes: BPS, BPAF, BADGE•H2O•HCl and BADGE. The proposed method may be an attractive alternative for application in large-scale human biomonitoring studies.

The Effects of Combined Exposure to Bisphenols and Perfluoroalkyls on Human Perinatal Stem Cells and the Potential Implications for Health Outcomes.

The present study investigates the impact of two endocrine disruptors, namely Bisphenols (BPs) and Perfluoroalkyls (PFs), on human stem cells. These chemicals leach from plastic, and when ingested through contaminated food and water, they interfere with endogenous hormone signaling, causing various diseases. While the ability of BPs and PFs to cross the placental barrier and accumulate in fetal serum has been documented, the exact consequences for human development require further elucidation. The present research work explored the effects of combined exposure to BPs (BPA or BPS) and PFs (PFOS and PFOA) on human placenta (fetal membrane mesenchymal stromal cells, hFM-MSCs) and amniotic fluid (hAFSCs)-derived stem cells. The effects of the xenobiotics were assessed by analyzing cell proliferation, mitochondrial functionality, and the expression of genes involved in pluripotency and epigenetic regulation, which are crucial for early human development. Our findings demonstrate that antenatal exposure to BPs and/or PFs may alter the biological characteristics of perinatal stem cells and fetal epigenome, with potential implications for health outcomes at birth and in adulthood. Further research is necessary to comprehend the full extent of these effects and their long-term consequences.

Construction of dual Z-scheme Bi2WO6/g-C3N4/black phosphorus quantum dots composites for effective bisphenol A degradation.

In this work, a novel dual Z-scheme Bi2WO6/g-C3N4/black phosphorus quantum dots (Bi2WO6/g-C3N4/BPQDs) composites were fabricated and utilized towards photocatalytic degradation of bisphenol A (BPA) under visible-light irradiation. Optimizing the content of g-C3N4 and BPQDs in Bi2WO6/g-C3N4/BPQDs composites to a suitable mass ratio can enhance the visible-light harvesting capacity and increase the charge separation efficiency and the transfer rate of excited-state electrons and holes, resulting in much higher photocatalytic activity for BPA degradation (95.6%, at 20 mg/L in 120 min) than that of Bi2WO6 (63.7%), g-C3N4 (25.0%), BPQDs (8.5%), and Bi2WO6/g-C3N4 (79.6%), respectively. Radical trapping experiments indicated that photogenerated holes (h+) and superoxide radicals (•O2-) played crucial roles in photocatalytic BPA degradation. Further, the possible degradation pathway and photocatalytic mechanism was proposed by analyzing the BPA intermediates. This work also demonstrated that the Bi2WO6/g-C3N4/BPQDs as effective photocatalysts was stable and have promising potential to remove environmental contaminants from real water samples.

EDCs trigger immune-neurotransmitter related gene expression, and cause histological damage in sensitive mud crab Macrophthalmus japonicus gills and hepatopancreas.

Endocrine-disrupting chemicals (EDCs), distributed at various concentrations in freshwater and marine ecosystems, affect the survival, reproduction, and behavior of wide ranges organisms. Most toxicology studies on EDCs have focused on the endocrine system of invertebrates, and research on invertebrate neurotransmitters is limited. In the present study, we investigated the expression of Macrophthalmus japonicus genes encoding γ-aminobutyric acid transporter subtype 2 (GAT-2) and glutamine synthetase (GS), which play important roles as neurotransmitters at synapses. We observed differences in the mRNA expression levels of GAT-2 and GS as well as histological changes in various tissues after exposure to bisphenol-A (BPA) and di-(2-ethylhexyl) phthalate (DEHP). The amino acid sequences of M. japonicus GAT-2 and GS formed separate branches in crustaceans, fish, insects, and mammals. M. japonicus GAT-2 and GS expression levels were highest in the gills, hepatopancreas, and stomach, and showed different between DEHP or BPA treatments. In particular, hepatopancreas GS expression on Day 1, the first step in the presynaptic process, was upregulated after BPA and DEHP exposure, while GAT-2, sequential step in the presynaptic process, was significantly elevated only in DEHP. After BPA treatments, gill GS expression was increased at all concentrations, whereas GAT-2 expression was overall down regulations. In contrast, in DEHP treatment groups hepatopancreatic GS and GAT-2 expression at Day 1 was only significantly higher and all groups including gill GS and GAT-2 expression were downregulation. Histological changes in the gills and hepatopancreas were observed in a concentration-dependent manner. Accordingly, BPA and DEHP exposure in crabs could be stimulate neurotransmitter gene expression and alter the morphological structure of gill and hepatopancreas.

Maternal Bisphenol A (BPA) Exposure Alters Cerebral Cortical Morphogenesis and Synaptic Function in Mice.

Early-life exposure to bisphenol A (BPA), synthetic compound used in polycarbonate plastic, is associated with altered cognitive and emotional behavior later in life. However, the brain mechanism underlying the behavioral deficits is unknown. Here, we show that maternal BPA exposure disrupted self-renewal and differentiation of neural progenitors during cortical development. The BPA exposure reduced the neuron number, whereas it increased glial cells in the cerebral cortex. Also, synaptic formation and transmission in the cerebral cortex were suppressed after maternal BPA exposure. These changes appeared to be associated with autophagy as a gene ontology analysis of RNA-seq identified an autophagy domain in the BPA condition. Mouse behavioral tests revealed that maternal BPA caused hyperactivity and social deficits in adult offspring. Together, these results suggest that maternal BPA exposure leads to abnormal cortical architecture and function likely by activating autophagy.

Sex-specific influence of maternal exposure to bisphenol A on sodium and fluid balance in response to dipsogenic challenges in rats.

The plasticizer bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. Human exposure to BPA occurs almost constantly. BPA is an endocrine disruptor that interferes in estrogen receptor functions. This is important for the developing brain, which is particularly sensitive to the estrogenic effects of BPA. Body fluid balance is maintained by a complex network of systems that regulate sodium and water intakes and electrolyte excretion. The development of these control systems occurs during early life and therefore, may be susceptible to changes in the uterine environment. The aim of this work was to study the effects of two low BPA doses in the dam, during pregnancy and lactation, on adult offspring drinking and sodium and urine excretion after dipsogenic challenge. Dams were exposed to BPA in drinking water to mimic the most likely route of human exposure. The results showed that BPA did not disrupt spontaneous fluid balance, but altered sodium and fluid intakes in the BPA offspring under osmotic challenges. In experiments, both 24h fluid deprivation and sodium depletion modified fluid ingestive response in BPA offspring compared to control offspring. The increased preference for 2.7% NaCl solution in male BPA offspring is similar to female control offspring, altered ingestive behavior appears to be due to feminization of males and "hyperfeminization" of female BPA offspring, as they drink more than female control offspring. Our results indicate that exposure to low doses of BPA in early life may disrupt the development of sex-specific drinking behaviors by altering the steroid programming of the brain, and this disruption affects males and females differently.

Increased bisphenol A levels in Thai children and adolescents with type 1 diabetes mellitus.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in children and adolescents continues to increase worldwide. The reason for this is unclear. In addition to the role of genetics, bisphenol A (BPA) has been investigated as a possible causal factor for T1DM. This study aimed to determine the correlation between urinary BPA levels and T1DM in Thai children and adolescents. METHODS: A cross-sectional study was conducted in T1DM patients who were followed at the endocrinology clinic at King Chulalongkorn Memorial Hospital from December 2018 to December 2019 and age-matched healthy controls. Urinary BPA levels were analyzed by high-performance liquid chromatography and adjusted by urine creatinine. Anthropometric data were measured in all participants and clinical data were collected for the T1DM patients. All participants completed a questionnaire regarding possible BPA exposures. Multivariate logistic regression analysis was used to estimate the adjusted odds ratio for T1DM. RESULTS: Seventy-five T1DM patients and 113 age-matched controls were included in the study. The mean age for T1DM and control groups were 14.8 ± 5.7 and 14.4 ± 6.2 years, respectively. The T1DM group had a significantly higher median (interquartile range) level of adjusted urinary BPA compared to the control (31.50 [7.87, 69.45] vs 10.1 [0, 54.01] µg/g creatinine, P = 0.02). Urinary BPA of 17 µg/g creatinine or more was significantly associated with TIDM, with adjusted odds ratio (95% Confident interval, CI) of 2.38 (1.27, 4.44), P = 0.006. CONCLUSIONS: Higher urinary BPA level is one of the possible risk factors for T1DM.