Deciphering the molecular mechanism of NLRP3 in BPA-mediated toxicity: Implications for targeted therapies.

Bisphenol-A (BPA), a pervasive industrial chemical used in polymer synthesis, is found in numerous consumer products including food packaging, medical devices, and resins. Detectable in a majority of the global population, BPA exposure occurs via ingestion, inhalation, and dermal routes. Extensive research has demonstrated the adverse health effects of BPA, particularly its disruption of immune and endocrine systems, along with genotoxic potential. This review focuses on the complex relationship between BPA exposure and the NOD-like receptor protein 3 (NLRP3) inflammasome, a multiprotein complex central to inflammatory disease processes. We examine how BPA induces oxidative stress through the generation of intracellular free radicals, subsequently activating NLRP3 signaling. The mechanistic details of this process are explored, including the involvement of signaling cascades such as PI3K/AKT, JAK/STAT, AMPK/mTOR, and ERK/MAPK, which are implicated in NLRP3 inflammasome activation. A key focus of this review is the wide-ranging organ toxicities associated with BPA exposure, including hepatic, renal, gastrointestinal, and cardiovascular dysfunction. We investigate the immunopathogenesis and molecular pathways driving these injuries, highlighting the interplay among BPA, oxidative stress, and the NLRP3 inflammasome. Finally, this review explores the emerging concept of targeting NLRP3 as a potential therapeutic strategy to mitigate the organ toxicities stemming from BPA exposure. This work integrates current knowledge, emphasizes complex molecular mechanisms, and promotes further research into NLRP3-targeted interventions.

Insights into mechanism of peroxymonosufate activation by Mo single-atom catalysts: Singlet oxygen evolution and role of Mo-N coordination.

Recently, the Fenton-like reaction using peroxymonosulfate (PMS) has been acknowledged as a potential method for breaking down organic pollutants. In this study, we successfully synthesized a highly efficient and stable single atom molybdenum (Mo) catalyst dispersed on nitrogen-doped carbon (Mo-NC-0.1). This catalyst was then utilized for the first time to activate PMS and degrade bisphenol A (BPA). The Mo-NC-0.1/PMS system demonstrated the ability to completely degrade BPA within just 20 min. Scavenging tests and density functional theory (DFT) calculations have demonstrated that the primary reactive oxygen species was singlet oxygen (1O2) produced by Mo-N4 sites. The self-cycling of Mo facilitated PMS activation and the transition from a free radical activation pathway to a non-radical pathway mediated by 1O2. Simultaneously, the nearby pyridinic N served as adsorption sites to immobilize BPA and PMS molecules. The exceptionally high catalytic activity of Mo-NC-0.1 derived from its unique Mo-N coordination, which markedly reduced the distance for 1O2 to migrate to the BPA molecules. The Mo-NC-0.1/PMS system effectively reduced the acute toxicity of BPA and exhibited excellent cycling stability with minimal leaching. This study presented a new catalyst with high selectivity for 1O2 generation and provided valuable insights for the application of single atom catalysts in PMS-based AOPs.

Centella asiatica mitigates the detrimental effects of Bisphenol-A (BPA) on pancreatic islets.

Bisphenol-A (BPA) is widely used in food packaging and household products, leading to daily human exposure and potential health risks including metabolic diseases like type 2 diabetes mellitus (T2DM). Understanding BPA's mechanisms and developing intervention strategies is urgent. Centella asiatica, a traditional herbal medicine containing pentacyclic triterpenoids, shows promise due to its antioxidant and anti-inflammatory properties, utilized for centuries in Ayurvedic therapy. We investigated the effect of Centella asiatica (CA) ethanol extract on BPA-induced pancreatic islet toxicity in male Swiss albino mice. BPA administration (10 and 100 µg/kg body weight, twice daily) for 21 days caused glucose homeostasis disturbances, insulin resistance, and islet dysfunction, which were partially mitigated by CA supplementation (200 and 400 mg/kg body weight). Additionally, heightened oxidative stress, elevated levels of proinflammatory cytokines, loss of mitochondrial membrane potential (MMP), abnormal cell cycle, and increased apoptosis were implicated in the detrimental impact of BPA on the endocrine pancreas which were effectively counteracted by CA supplementation. In summary, CA demonstrated a significant ability to mitigate BPA-induced apoptosis, modulate redox homeostasis, alleviate inflammation, preserve MMP, and regulate the cell cycle. As a result, CA emerged as a potent agent in neutralizing the diabetogenic effects of BPA to a considerable extent.

Endocrine disrupting chemical Bisphenol A and its association with cancer mortality: a prospective cohort study of NHANES.

Introduction: There is evidence suggesting that Bisphenol A (BPA) is associated with increased all-cause mortality in adults. However, the specific nature of the relationship between BPA exposure and cancer mortality remains relatively unexplored. Methods: The National Health and Nutrition Examination Survey (NHANES) dataset was used to recruit participants. Urinary BPA was assessed using liquid chromatography-mass spectrum (LC-MS). Through the use of multivariable Cox proportional hazard regressions and constrained cubic splines, the relationships between urine BPA and death from all causes and cancer were investigated. Results: This study has a total of 8,035 participants, and 137 died from cancers after a 7.5-year follow-up. The median level of BPA was 2.0 g/mL. Urinary BPA levels were not independently associated with all-cause mortality. For cancer mortality, the second quartile's multivariable-adjusted hazard ratio was 0.51 (95% confidence interval: 0.30 to 0.86; p = 0.011) compared to the lowest quartile. The restricted cubic splines showed that the association was nonlinear (p for nonlinearity = 0.028) and the inflection point was 1.99 ng/mL. Conclusion: Urinary BPA exposure was U-shaped associated with the risk of cancer mortality, and a lower level of BPA less than 1.99 ng/mL was associated with a higher risk of cancer mortality.

Tuning interfacial oxygen vacancy level of bismuth oxybromide to enhance photocatalytic degradation of bisphenol A.

Oxygen vacancies (OVs) have garnered significant interest for their role as active sites, enhancing the catalytic efficiency of various catalysts. Despite their widespread application in environmental purification processes, the generation of OVs conventionally depends on high-temperature conditions and strong reducing agents for the extraction of surface partial oxygen atoms from catalysts. In this work, bismuth oxybromide (BiOBr) nanosheets with varying levels of OVs were synthesized via a simple and effective solvothermal method. This novel method affords precise control over the conduction band (CB) and valence band (VB) positions of BiOBr. The presence of different OVs exhibited varying photocatalytic efficiencies in the degradation of bisphenol A (BPA) under visible light irradiation, with higher levels of OVs resulting in superior photocatalytic performance. Furthermore, radical scavenger experiments demonstrated that superoxide oxides (O2•-) and holes (h+) were the primary reactive oxygen species for BPA degradation. Additionally, BiOBr-OVs exhibited excellent anti-interference and stability in water matrices containing diverse inorganic anions and organic compounds. This work provides a simple and effective approach for the fine-regulating of catalysts through interfacial defect engineering, paving the way for their practical application in environmental decontamination.

Photocatalytic and electrocatalytic degradation of bisphenol A in the presence of graphene/graphene oxide-based nanocatalysts: A review.

Bisphenol A (BPA), a widely recognized endocrine disrupting compound, has been discovered in drinking water sources/finished water and domestic wastewater influent/effluent. Numerous studies have shown photocatalytic and electrocatalytic oxidation to be very effective for the removal of BPA, particularly in the addition of graphene/graphene oxide (GO)-based nanocatalysts. Nevertheless, the photocatalytic and electrocatalytic degradation of BPA in aqueous solutions has not been reviewed. Therefore, this review gives a comprehensive understanding of BPA degradation during photo-/electro-catalytic activity in the presence of graphene/GO-based nanocatalysts. Herein, this review evaluated the main photo-/electro-catalytic degradation mechanisms and pathways for BPA removal under various water quality/chemistry conditions (pH, background ions, natural organic matter, promotors, and scavengers), the physicochemical characteristics of various graphene/GO-based nanocatalysts, and various operating conditions (voltage and current). Additionally, the reusability/stability of graphene/GO-based nanocatalysts, hybrid systems combined with ozone/ultrasonic/Fenton oxidation, and prospective research areas are briefly described.

Critical role of endoplasmic reticulum stress on bisphenol A-induced cytotoxicity in human keratinocyte HaCaT cells.

Bisphenol A (BPA) is widely used in plastic and paper products, and its exposure can occur through skin contact or oral ingestion. The hazardous effects of BPA absorbed through the skin may be more severe; however, few studies have investigated the skin toxicity of BPA. This study investigated the effects of BPA on human epidermal keratinocyte cell lines, which is relevant for skin exposure. BPA treatment reduced cell viability in a time- and concentration-dependent manner and elevated oxidative and endoplasmic reticulum (ER) stress. N-acetylcysteine (NAC), an oxidative stress inhibitor, reduced BPA-induced reactive oxygen species (ROS) levels. However, only 10% of the decreased cell viability was restored at the highest NAC concentration. Treatment with tauroursodeoxycholic acid (TUDCA), which is an ER stress inhibitor, effectively countered the increase in ER stress-related proteins induced by BPA. Moreover, TUDCA treatment led to a reduction in oxidative stress, as demonstrated by the decrease in ROS levels, maintenance of mitochondrial membrane potential, and modulation of stress signaling proteins. Consequently, TUDCA significantly improved BPA-induced cytotoxicity in a concentration-dependent manner. Notably, combined treatment using TUDCA and NAC further reduced the BPA-induced ROS levels; however, no significant difference in cell viability was observed compared with that for TUDCA treatment alone. These findings indicated that the oxidative stress observed following BPA exposure was exacerbated by ER stress. Moreover, the principal factor driving BPA-induced cytotoxicity was indeed ER stress, which has potential implications for developing therapeutic strategies for diseases associated with similar stress responses.

The Selective Removal of Bisphenol A Using a Magnetic Adsorbent Fused with Bisphenol A-Binding Peptides.

The potential of bisphenol A (BPA)-binding peptides fused to magnetic beads is demonstrated as novel adsorbents that are reusable and highly selective for BPA removal from aqueous environments, in which various interfering substances coexist. Magnetic beads harboring peptides (peptide beads) showed a higher BPA removal capacity (8.6 mg/g) than that of bare beads without peptides (2.0 mg/g). The BPA adsorption capacity of peptide beads increased with the number of peptides fused onto the beads, where monomeric, dimeric, or trimeric repeats of a BPA-binding peptide were fused to magnetic beads. The BPA-adsorbing beads were regenerated using a methanol-acetic acid mixture, and after six regeneration cycles, the adsorption capacity remained above 87% of its initial capacity. The selective removal of BPA was confirmed in the presence of BPA analogs with high structural similarity (bisphenol F and bisphenol S) or in synthetic wastewater. The present work is a pioneering study that investigates the selective affinity of peptides to remove specific organics with high selectivity from complex environmental matrices.

Single and mixture effects of bisphenol A and benzophenone-3 on in vitro T helper cell differentiation.

Immune homeostasis is key to guarantee that the immune system can elicit effector functions against pathogens and at the same time raise tolerance towards other antigens. A disturbance of this delicate balance may underlie or at least trigger pathologies. Endocrine disrupting chemicals (EDCs) are increasingly recognized as risk factors for immune dysregulation. However, the immunotoxic potential of specific EDCs and their mixtures is still poorly understood. Thus, we aimed to investigate the effect of bisphenol A (BPA) and benzophenone-3 (BP-3), alone and in combination, on in vitro differentiation of T helper (TH)17 cells and regulatory T (Treg) cells. Naïve T cells were isolated from mouse lymphoid tissues and differentiated into the respective TH population in the presence of 0.001-10 µM BP-3 and/or 0.01-100 µM BPA. Cell viability, proliferation and the expression of TH lineage specific transcription factors and cytokines was measured by flow cytometry and CBA/ELISA. Moreover, the transcription of hormone receptors as direct targets of EDCs was quantified by RT-PCR. We found that the highest BPA concentration adversely affected TH cell viability and proliferation. Moreover, the general differentiation potential of both TH populations was not altered in the presence of both EDCs. However, EDC exposure modulated the emergence of TH17 and Treg cell intermediate states. While BPA and BP-3 promoted the development of TH1-like TH17 cells under TH17-differentiating conditions, TH2-like Treg cells occurred under Treg polarization. Interestingly, differential effects could be observed in mixtures of the two tested compounds compared with the individual compounds. Notably, estrogen receptor ß expression was decreased under TH17-differentiating conditions in the presence of BPA and BP-3 as mixture. In conclusion, our study provides solid evidence for both, the immune disruptive potential and the existence of cumulative effects of real nature EDC mixtures on T cell in vitro differentiation.

Effects of salinity on behavior and reproductive toxicity of BPA in adult marine medaka.

Salinity is an important environmental factor influencing the toxicity of chemicals. Bisphenol A (BPA) is an environmental endocrine disruptor with adverse effects on aquatic organisms, such as fish. However, the influence of salinity on the biotoxicity of BPA and the underlying mechanism are unclear. In this study, we exposed marine medaka (Oryzias melastigma) to BPA at different salinities (0 psu, 15 psu, and 30 psu) for 70days to investigate the toxic effects. At 0 psu salinity, BPA had an inhibitory effect on the swimming behavior of female medaka. At 15 psu salinity, exposure to BPA resulted in necrotic cells in the ovaries but not on the spermatozoa. In addition, BPA exposure changed the transcript levels of genes related to the nervous system (gap43, elavl3, gfap, mbpa, and α-tubulin) and the hypothalamic-pituitary-gonadal (HPG) axis (fshr, lhr, star, arα, cyp11a, cyp17a1, cyp19a, and erα); the expression changes differed among salinity levels. These results suggest that salinity influences the adverse effects of BPA on the nervous system and reproductive system of medaka. These results emphasize the importance of considering the impact of environmental factors when carrying out ecological risk assessment of pollutants.

Low-dose BPA-induced neuronal energy metabolism dysfunction and apoptosis mediated by PINK1/parkin mitophagy pathway in juvenile rats.

Bisphenol A (BPA) is related to neurological disorders involving mitochondrial dysfunction, while the mechanism remains elusive. Therefore, we explored it through in vitro and in vivo experiments. In vitro, hippocampal neurons derived from neonatal rats of different genders were exposed to 1-100 nM and 100 µM BPA, autophagy activator Rapa and inhibitor 3-MA for 7 d. The results suggested that even nanomolar BPA (1-100 nM) disturbed Ca2+ homeostasis and damaged the integrity of mitochondrial cristae in neurons (p < 0.05). Furthermore, BPA increased the number of autophagic lysosomes, LC3II/LC3I ratio, and p62 expression, and decreased parkin expression (p < 0.05), suggesting that the entry of damaged mitochondria into autophagic pathway was prompted, while the autophagic degradation pathway was blocked. This further disrupts neuronal energy metabolism and promotes neuronal apoptosis. However, Rapa attenuated the adverse effects caused by BPA, while 3-MA exacerbated these reactions. In vivo, exposure of juvenile rats to 0.5, 50, 5000 µg/kg‧bw/day BPA during PND 7-21 markedly impaired the structure of hippocampal mitochondria, increased the number of autophagosomes, the rate of neuronal apoptosis, and the expression levels of pro-apoptotic proteins Cyt C, Bax, Bak1, and Caspase3, and decreased the expression of anti-apoptotic protein Bcl2 (p < 0.05). Particularly, male rats are more sensitive to low-dose BPA than females. Overall, environmental-doses BPA can induce the imbalance of energy metabolism in hippocampal neurons via PINK1/parkin mitophagy, thereby inducing their apoptosis. Importantly, this study provides a theoretical basis for attenuating BPA-related neurological diseases.

Estradiol-17ß and bisphenol A affect growth and mineralization in early life stages of seabass.

Natural and synthetic estrogens are contaminants present in aquatic ecosystems. They can have significant consequences on the estrogen-sensitive functions of organisms, including skeletal development and growth of vertebrate larvae. Synthetic polyphenols represent a group of environmental xenoestrogens capable of binding the receptors for the natural hormone estradiol-17ß (E2). To better understand how (xeno-)estrogens can affect the skeleton in fish species with high ecological and commercial interest, 16 days post-hatch larvae of the seabass were experimentally exposed for 7 days to E2 and Bisphenol A (BPA), both used at the regulatory concentration of surface water quality (E2: 0.4 ng.L-1, BPA: 1.6 µg.L-1) or at a concentration 100 times higher. Skeletal mineralization levels were evaluated using Alizarin red staining, and expression of several genes playing key roles in growth, skeletogenesis and estrogen signaling pathways was assessed by qPCR. Our results show that E2 exerts an overall negative effect on skeletal mineralization at the environmental concentration of 0.4 ng.L-1, correlated with an increase in the expression of genes associated only with osteoblast bone cells. Both BPA exposures inhibited mineralization with less severe effects and modified bone homeostasis by regulating the expression of gene encoding osteoblasts and osteoclasts markers. Our results demonstrate that environmental E2 exposure inhibits larval growth and has an additional inhibitory effect on skeleton mineralization while both BPA exposures have marginal inhibitory effect on skeletal mineralization. All exposures have significant effects on transcriptional levels of genes involved in the skeletal development of seabass larvae.

Dual-signal amplified electrochemical aptasensor based on Au/MrGO and DNA nanospheres for ultra-sensitive detection of BPA without directly modified working electrode.

Rapid and sensitive analysis of bisphenol A (BPA) is essential for preventing health risks to humans and animals. Hence, a signal-amplified electrochemical aptasensor without repetitive polishing and modification of working electrode was developed for BPA using Au-decorated magnetic reduced graphene oxide (Au/MrGO)-based recognition probe (RP) and DNA nanospheres (DNS)-based signal probe (SP) cooperative signal amplification. The DNS served as a signal molecule carrier and signal amplifier, while Au/MrGO acted as a signal amplifier and excellent medium for magnetic adsorption and separation. Moreover, utilizing the excellent magnetic properties of Au/MrGO eliminates the need for repetitive polishing and multi-step direct modification of the working electrode while ensuring that all detection processes take place in solution and that used Au/MrGO can be easily recycled. The proposed aptasensor exhibited not only good stability and selectivity, but also excellent sensitivity with a limit of detection (LOD) of 8.13 fg/mL (S/N=3). The aptasensor's practicality was proven by spiking recovery tests on actual water samples and comparing the results with those detected by HPLC. The excellent sensitivity and selectivity make this aptasensor an alternative and promising avenue for rapid detection of BPA in environmental monitoring.

Connecting Bisphenol A Exposure to PCOS: Findings from a Case-Control Investigation.

Polycystic Ovary Syndrome (PCOS) is a multifaceted condition influenced by genetic, hormonal, and environmental factors. Among environmental factors, Bisphenol A (BPA)-a recognized endocrine disruptor-has been implicated in the development of PCOS. The study aimed to compare BPA levels in women diagnosed with PCOS with those in healthy controls, using the high-performance liquid chromatography (HPLC) technique. The study involved 80 women diagnosed with PCOS and 50 healthy control participants. Demographic and biochemical parameters were recorded, including age, Body Mass Index (BMI), and levels of testosterone, estradiol, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin (PRL), Dehydroepiandrosterone Sulfate (DHEA-S), Thyroid Stimulating Hormone (TSH), and Insulin Resistance as measured by the Homeostatic Model Assessment (HOMA-IR). Furthermore, BPA levels were measured using the HPLC technique. Women with PCOS exhibited significantly higher mean age and BMI compared to healthy controls (p = 0.01, p < 0.0001, respectively). Additionally, higher levels of testosterone (p = 0.04), LH (p = 0.03) and BPA (p < 0.0001) were observed in women with PCOS. However, estradiol, FSH, PRL, LH/FSH ratio, DHEA-S, and TSH levels were not significantly different between the two groups. HOMA-IR levels were not recorded for the control group. A notable positive relationship emerged between Bisphenol A and luteinizing hormone (LH) levels (r = 0.23, p = 0.03), also significant negative correlation appeared between Bisphenol A and thyroid-stimulating hormone (TSH) levels. This study found that women with PCOS have elevated BPA levels compared with healthy controls, showing a need for further research on the relationship between BPA exposure and the development of PCOS.

Comprehensive understanding of the role of GPER in estrogen receptor-alpha negative breast cancer.

G protein-coupled estrogen receptor (GPER) plays a prominent role in facilitating the rapid, non-genomic signaling of estrogens in breast cancer cells. Herein, a comprehensive overview of the role of GPER in ER-ɑ-negative breast cancer is provided. Activation of GPER affected proliferation, metastasis and epithelial mesenchymal transition in ER-ɑ negative breast cancer cells. Clinical studies have demonstrated that GPER positivity was strongly correlated with larger tumor size and advanced clinical stage, suggesting that GPER/ERK signaling may play a role in promoting tumor progression. Strong evidence existed that environmental contaminants like bisphenol A have a carcinogenic potential mediated by GPER activation. The complexity of the cross talk between GPER and other receptors including ER-ß, ER-α36, Estrogen-related receptor α (ERRα) and androgen receptor has been discussed. The potential utility of small molecules and phytoestrogens targeting GPER, adds valuable insights into its therapeutic potential. This review holds promises in advancing our understanding of GPER role in ER-ɑ-negative breast cancer. Overall, the consequences of GPER activation are still an area of active research and the implication are not entirely clear.

Description of Solvent-Extractable Chemicals in Thermal Receipts and Toxicological Assessment of Bisphenol S and Diphenyl Sulfone.

Research on thermal receipts has previously focused on the toxic effects of dermal exposure from the most publicized developers (e.g., bisphenol A (BPA) and bisphenol S (BPS)), while no studies have reported on the other solvent-extractable compounds therein. Diphenyl sulfone (DPS) is a sensitizer added to thermal receipts, but little is known about DPS concentrations in receipts or potential toxicity. Here, we quantified BPA, BPS, and DPS concentrations and tentatively identified the solvent-extractable compounds of thermal receipts collected from three South Dakota (USA) cities during 2016-2017. An immortalized chicken hepatic cell line, cultured as 3D spheroids, was used to screen effects of DPS, BPS, and 17ß estradiol (E2; 0.1-1000 µM) on cell viability and gene expression changes. These chemicals elicited limited cytotoxicity with LC50 values ranging from 113 to 143 µM, and induced dysregulation in genes associated with lipid and bile acid homeostasis. Taken together, this study generated novel information on solvent-extractable chemicals from thermal receipts and toxicity data for DPS.

Decreased Treg cells induced by bisphenol A is associated with up-regulation of PI3K/Akt/mTOR signaling pathway and Foxp3 DNA methylation in spleen of adolescent mice.

The current study aimed to explore whether bisphenol A (BPA) exposure aggravated the decrease in Tregs induced by ovalbumin (OVA) in adolescent female mouse models of asthma, and whether the process was associated with mTOR-mediated signaling pathways and DNA methylation levels. A total of 40 female C57BL/6 mice at the age of four weeks were used and divided into five groups after 1 week of domestication. Each group consisted of eight mice: the control group, OVA group, OVA + BPA (0.1 µg mL-1) group, OVA + BPA (0.2 µg mL-1) group, and OVA + BPA (0.4 µg mL-1) group. Results revealed that Foxp3 protein levels decreased in the spleens of mice exposed to BPA compared to those in the OVA group. After an elevation in BPA dose, the mRNAs of methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b) were gradually upregulated. The mechanism was related to the activity of TLR4/NF-κB and PI3K/Akt/mTOR signaling pathways and the enhancement of Foxp3 DNA methylation. Our results, collectively, provided a new view for studying the mechanisms underlying BPA exposure-induced immune dysfunction. Investigation of the regulatory mechanisms of DNA methylation in the abnormal Th immune response caused by BPA exposure could help reveal the causes and molecular mechanisms underlying the high incidence of allergic diseases in children in recent years.

Long-term exposure of endangered Danube sturgeon (Acipenser gueldenstaedtii) to bisphenol A (BPA): growth, behavioral, histological, genotoxic, and hematological evaluation.

Danube sturgeon (Acipenser gueldenstaedtii) which is identified as endangered species can be exposed to pollutants such as bisphenol A (BPA) that have a disruptive effect on the endocrine system at any time. Starting from this motivation, the current study focused on BPA toxicity in A. gueldenstaedtii juvenile individuals and its adverse effects in sub-lethal concentration. The median lethal concentration (LC50) of BPA was 5.03 mg/L in 96th hour. In the chronic period, 0.625 mg/L and 1.25 mg/L BPA concentrations were evaluated based on the result of acute study. Accordingly, growth performance was significantly decreased in BPA groups (1.25 mg/L BPA group was significantly lowest) compared to control (p < 0.05). In the acute period, behavioral disorders were standing at the bottom/corner of tank, slowing and stopping of gill movement, decreased response to stimuli, and death, respectively. While vacuolization was severe in the liver tissue of the fish in the acute period, intense necrosis and melanomacrophage centers were observed in the chronic period. In terms of genotoxicity, longer DNA migration was observed in all groups exposed to BPA than in the control group. In addition, lower erythrocyte and hemoglobin were observed in the BPA groups compared to control. As a result, the current study revealed toxic effect of BPA on A. gueldenstaedtii juvenile individuals and its negative results on fish physiology.

Degradation mechanisms and toxicity determination of bisphenol A by FeOx-activated peroxydisulfate under ultraviolet light.

Ultraviolet light (UV)-assisted advanced oxidation processes (AOPs) are commonly used to degrade organic contaminants. However, this reaction system's extensive comprehension of the degradation mechanisms and toxicity assessment remains inadequate. This study focuses on investigating the degradation mechanisms and pathways of bisphenol A (BPA), generation of reactive oxygen species (ROS), and toxicity of degradation intermediates in UV/PDS/ferrous composites (FeOx) systems. The degradation rate of BPA gradually increased from the initial 11.92% to 100% within 120 min. Sulfate radicals (SO4.-), hydroxyl radicals (.OH), superoxide anions (O2.-), and singlet oxygen (1O2) were the primary factors in the photocatalytic degradation of BPA in the UV/PDS/FeOx systems. The main reactions of BPA in this system were deduced to be ß-bond cleavage, hydroxyl substitution reaction, hydrogen bond cleavage, and oxidation reaction. A trend of decreasing toxicity for the degradation intermediates of BPA was observed according to the toxicity investigations. The efficient degradation of BPA in UV/PDS/FeOx systems provided theoretical data for AOPs, which will improve the understanding of organic contaminants by FeOx in natural industry wastewater.

Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem Cells.

PURPOSE: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. MATERIALS AND METHODS: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. RESULTS: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. CONCLUSIONS: Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.