Selective lignin arylation for biomass fractionation and benign bisphenols.

Lignocellulose is mainly composed of hydrophobic lignin and hydrophilic polysaccharide polymers, contributing to an indispensable carbon resource for green biorefineries1,2. When chemically treated, lignin is compromised owing to detrimental intra- and intermolecular crosslinking that hampers downstream process3,4. The current valorization paradigms aim to avoid the formation of new C-C bonds, referred to as condensation, by blocking or stabilizing the vulnerable moieties of lignin5-7. Although there have been efforts to enhance biomass utilization through the incorporation of phenolic additives8,9, exploiting lignin's proclivity towards condensation remains unproven for valorizing both lignin and carbohydrates to high-value products. Here we leverage the proclivity by directing the C-C bond formation in a catalytic arylation pathway using lignin-derived phenols with high nucleophilicity. The selectively condensed lignin, isolated in near-quantitative yields while preserving its prominent cleavable ß-ether units, can be unlocked in a tandem catalytic process involving aryl migration and transfer hydrogenation. Lignin in wood is thereby converted to benign bisphenols (34-48 wt%) that represent performance-advantaged replacements for their fossil-based counterparts. Delignified pulp from cellulose and xylose from xylan are co-produced for textile fibres and renewable chemicals. This condensation-driven strategy represents a key advancement complementary to other promising monophenol-oriented approaches targeting valuable platform chemicals and materials, thereby contributing to holistic biomass valorization.

Kaempferol alleviates bisphenol A reproductive toxicity in rats in a dose-dependent manner.

BACKGROUND: Endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), are a major cause of male infertility by disrupting spermatogenesis. OBJECTIVE: Here, we examined the potential protective benefits of kaempferol (KMF), a flavonol known for its antioxidant properties, on BPA-induced reproductive toxicity in adult male rats. METHODS: Human skin fibroblast cells (HNFF-P18) underwent cell viability assays. Thirty-five male Wistar rats were assigned to four groups: 1) control, 2) BPA (10 mg/kg), 3,4) BPA, and different dosages of KMF (1 and 10 mg/kg). The study examined the rats' testosterone serum level, antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), oxidative markers malondialdehyde (MDA) and total antioxidant capacity (TAC), body weight, weight ratios of testis and prostate, and histopathological examinations. RESULTS: The study revealed that using KMF to treat rats exposed to BPA increased cell viability. Moreover, the rats' testosterone levels, which BPA reduced, showed a significant increase after KMF was included in the treatment regimen. Treatment with BPA led to oxidative stress and tissue damage, but simultaneous treatment with KMF restored the damaged tissue to its normal state. Histopathology studies on testis and prostate tissues showed that KMF had an ameliorative impact on BPA-induced tissue damage. CONCLUSIONS: The research suggests that KMF, a flavonol, could protect male rats from the harmful effects of BPA on reproductive health, highlighting its potential healing properties.

The Impact of Bisphenol A on the Anaerobic Sulfur Transformation: Promoting Sulfur Flow and Toxic H2S Production.

Bisphenol A (BPA), as a typical leachable additive from microplastics and one of the most productive bulk chemicals, is widely distributed in sediments, sewers, and wastewater treatment plants, where active sulfur cycling takes place. However, the effect of BPA on sulfur transformation, particularly toxic H2S production, has been previously overlooked. This work found that BPA at environmentally relevant levels (i.e., 50-200 mg/kg total suspended solids, TSS) promoted the release of soluble sulfur compounds and increased H2S gas production by 14.3-31.9%. The tryptophan-like proteins of microbe extracellular polymeric substances (EPSs) can spontaneously adsorb BPA, which is an enthalpy-driven reaction (ΔH = -513.5 kJ mol-1, ΔS = -1.60 kJ mol-1K -1, and ΔG = -19.52 kJ mol-1 at 35 °C). This binding changed the composition and structure of EPSs, which improved the direct electron transfer capacity of EPSs, thereby promoting the bioprocesses of organic sulfur hydrolysis and sulfate reduction. In addition, BPA presence enriched the functional microbes (e.g., Desulfovibrio and Desulfuromonas) responsible for organic sulfur mineralization and inorganic sulfate reduction and increased the abundance of related genes involved in ATP-binding cassette transporters and sulfur metabolism (e.g., Sat and AspB), which promoted anaerobic sulfur transformation. This work deepens our understanding of the interaction between BPA and sulfur transformation occurring in anaerobic environments.

Granulosa cells undergo BPA-induced apoptosis in a miR-21-independent manner.

Bisphenol A (BPA) is a harmful endocrine disrupting compound that alters not only classical cellular mechanisms but also epigenetic mechanisms. Evidence suggests that BPA-induced changes in microRNA expression can explain, in part, the changes observed at both the molecular and cellular levels. BPA is toxic to granulosa cells (GCs) as it can activate apoptosis, which is known to contribute to increased follicular atresia. miR-21 is a crucial antiapoptotic regulator in GCs, yet the exact function in a BPA toxicity model remains unclear. BPA was found to induce bovine GC apoptosis through the activation of several intrinsic factors. BPA reduced live cells counts, increased late apoptosis/necrosis, increased apoptotic transcripts (BAX, BAD, BCL-2, CASP-9, HSP70), increased the BAX/Bcl-2 ratio and HSP70 at the protein level, and induced caspase-9 activity at 12 h post-exposure. miR-21 inhibition increased early apoptosis and, while it did not influence transcript levels or caspase-9 activity, it did elevate the BAX/Bcl-2 protein ratio and HSP70 in the same manner as BPA. Overall, this study shows that miR-21 plays a molecular role in regulating intrinsic mitochondrial apoptosis; however, miR-21 inhibition did not make the cells more sensitive to BPA. Therefore, apoptosis induced by BPA in bovine GCs is miR-21 independent.

Influences of bisphenol A on hydrogen production from food waste by thermophilic dark fermentation.

The extensive use of plastic products in food packaging and daily life makes them inevitably enter the treatment process of food waste (FW). Plasticizer as a new pollutant is threatening the dark fermentation of FW. Our study showed that bisphenol A (BPA) at > 250 mg/L had a significant inhibition on hydrogen production from FW by thermophilic dark fermentation. The endogenous ATP content and lactate dehydrogenase (LDH) release showed that high level of BPA not only inhibited the growth of hydrogen-producing consortium, but also led to cell death. In addition, BPA mainly affects the hydrogen-producing consortium by reducing cell membrane fluidity, damaging cell membrane integrity and reducing cell membrane potential, resulting in cell death. This study provides some new insights into the mechanism of the effect of BPA on hydrogen production from FW by thermophilic dark fermentation, and lays the foundation on the utilization of FW.

Hydrogel immobilized bacteria@MOFs composite towards Bisphenol A degradation and the interconnection mechanism elucidation.

Bisphenol A (BPA) degradation efficiency by bacteria or by metal-organic-frameworks (MOFs) catalyzed persulfate (PMS) oxidation have been studied intensively. However, their synergistic effect on BPA degradation was less reported. In this study, we combined previously synthesized CNT-hemin/Mn-MOF with an BPA degrading bacteria SQ-2 to form a composite (SQ-2@MOFs). CNT-hemin/Mn-MOF in the composite catalyzed little PMS to promote the degradation efficiency of SQ-2 on BPA. Results indicated SQ-2@MOFs significantly accelerated BPA degradation rate than SQ-2 alone. Furthermore, SQ-2@MOFs composite was successfully immobilized in hydrogel to achieve better degradation performance. Immobilized SQ-2@MOFs could almost completely degrade 1-20 mg/L BPA within 24 h and completely degrade 5 mg/L BPA at pH 4-8. Besides, degradation byproducts also reduced by immobilized SQ-2@MOFs, which promoted the cleaner biodegradation of BPA. Metabolomics and multiple chemical characterization results revealed the interconnection mechanism between CNT-hemin/Mn-MOFs, SQ-2 and hydrogel. CNT-hemin/Mn-MOF helped SQ-2 degrade BPA into more biodegradable products, promoted electron transfer, and augmented BPA degradation ability of SQ-2 itself. SQ-2 enabled the surface electronegativity of SQ-2@MOFs more suitable for BPA contact. Meanwhile, SQ-2 avoided the loss of Fe and Mn of CNT-hemin/Mn-MOF. Hydrogel augmented the above synergistic effect. This study provided new perspective for the development of biodegradation materials through interdisciplinary integration.

Accumulation of Bisphenol A® by Pleurotus spp.-Flow Injection Analysis.

A specific feature of mushrooms (including those of the genus Pleurotus) is their natural ability to absorb and accumulate many chemical substances present in their immediate environment, which makes them an excellent natural sorption material. Hence, fruiting bodies of mushrooms have been recognized for years as excellent indicators of the environment, reflecting its current state. Nevertheless, mushrooms can accumulate both health-promoting substances, such as bioelements, and toxic substances, such as heavy metals and organic compounds, including bisphenol A® (BPA). This organic chemical compound in the phenol group, although it has been withdrawn in the EU since 2010, is widely present in the environment around us. In the present experiment, we aimed to determine the effect of adding BPA to liquid media for in vitro cultures of Pleurotus spp. The biomass increases were determined. Moreover, the degrees of adsorption and desorption of BPA from the obtained freeze-dried biomass in two different environments (neutral and acidic) were determined as a function of time. This is the first study to determine the bioavailability of adsorbed BPA in obtained biomass by extracting the mycelium into artificial digestive juices in a model digestive system. BPA was added to the liquid Oddoux medium in the following amounts: 0.01, 0.5, and 0.5 g/250 mL of medium. The amounts of adsorbed and desorbed BPA were determined by flow injection analysis (FIA) with amperometric detection. The addition of BPA to the substrate reduced the biomass growth in each of the discussed cases. BPA adsorption by the mycelium occurred at over 90% and depended on the morphology of the mushroom (structure, surface development, and pore size). BPA desorption depended on the pH of the environment and the desorption time. Mushrooms are an excellent natural remedial material, but BPA is extracted into artificial digestive juices; therefore, consuming mushrooms from industrialized areas may have health consequences for our bodies.

Bacterial bioremediation as a sustainable strategy for the mitigation of Bisphenol-A.

In the era dominated by plastic, the widespread use of plastic in our daily lives has led to a growing accumulation of its degraded byproducts, such as microplastics and plastic additives like Bisphenol A (BPA). BPA is recognized as one of the earliest man-made substances that exhibit endocrine-disrupting properties. It is frequently employed in the manufacturing of epoxy resins, polycarbonates, dental fillings, food storage containers, infant bottles, and water containers. BPA is linked to a range of health issues including obesity, diabetes, chronic respiratory illnesses, cardiovascular diseases, and reproductive abnormalities. This study examines the bacterial bioremediation of the BPA, which is found in many sources and is known for its hazardous effects on the environment. The metabolic pathways for the breakdown of BPA in important bacterial strains were hypothesized based on the observed altered intermediate metabolites during the degradation of BPA. This review discusses the enzymes and genes involved in the bacterial degradation of BPA. The utilization of naturally occurring microorganisms is the most efficient and cost-effective method due to their selectivity of strains, ensuring sustainability.

Exposure to phthalate metabolites, bisphenol A, and psychosocial stress mixtures and pregnancy outcomes in the Atlanta African American maternal-child cohort.

BACKGROUND: Consumer products are common sources of exposure for phthalates and bisphenol A (BPA), which disrupt the endocrine system. Psychosocial stressors have been shown to amplify the toxic effects of endocrine disruptors but, information is limited among African Americans (AAs), who experience the highest rates of adverse pregnancy outcomes and are often exposed to the highest levels of chemical and non-chemical stressors. We examined the association between an exposure mixture of phthalate metabolites, BPA, and psychosocial stressors with gestational age at delivery and birthweight for gestational age z-scores in pregnant AA women. STUDY DESIGN: Participants were enrolled in the Atlanta African American Maternal-Child Cohort (N = 247). Concentrations of eight phthalate metabolites and BPA were measured in urine samples collected at up to two timepoints during pregnancy (8-14 weeks gestation and 20-32 weeks gestation) and were averaged. Psychosocial stressors were measured using self-reported, validated questionnaires that assessed experiences of discrimination, gendered racial stress, depression, and anxiety. Linear regression was used to estimate individual associations between stress exposures (chemical and psychosocial) and birth outcomes. We leveraged quantile g-computation was used to examine joint effects of chemical and stress exposures on gestational age at delivery (in weeks) and birthweight for gestational age z-scores. RESULTS: A simultaneous increase in all phthalate metabolites and BPA was associated with a moderate reduction in birthweight z-scores (mean change per quartile increase = -0.22, 95% CI = -0.45, 0.0). The association between our exposure mixture and birthweight z-scores became stronger when including psychosocial stressors as additional exposures (mean change per quantile increase = -0.35, 95% CI = -0.61, -0.08). Overall, we found null associations between exposure to chemical and non-chemical stressors with gestational age at delivery. CONCLUSIONS: In a prospective cohort of AA mother-newborn dyads, we observed that increased prenatal exposure to phthalates, BPA, and psychosocial stressors were associated with adverse pregnancy outcomes.

Longitudinal effects of prenatal exposure to plastic-derived chemicals and their metabolites on asthma and lung function from childhood into adulthood.

BACKGROUND AND OBJECTIVE: Environmental exposure to phthalates and bisphenol A (BPA), chemicals used in the production of plastics, may increase risk for asthma and allergies. However, little is known about the long-term effects of early life exposure to these compounds. We investigated if prenatal exposure to these compounds was associated with asthma, allergy and lung function outcomes from early childhood into adulthood in a cohort study. METHODS: Maternal serum samples collected from 846 pregnant women in the Raine Study were assayed for BPA and phthalate metabolites. The children of these women were followed up at 5, 13 and 22 years where spirometry and respiratory questionnaires were conducted to determine asthma and allergy status. Lung function trajectories were derived from longitudinal spirometry measurements. Multinomial logistic regression and weighted quantile sum regression was used to test associations of individual and chemical mixtures with asthma phenotypes and lung function trajectories. RESULTS: Effects of prenatal BPA and phthalates on asthma phenotypes were seen in male offspring, where BPA was associated with increased risk for persistent asthma, while mono-iso-butyl phthalate and mono-iso-decyl phthalate was associated with increased risk for adult asthma. Prenatal BPA had no effect on lung function trajectories, but prenatal phthalate exposure was associated with improved lung function. CONCLUSION: Prenatal BPA exposure was associated with increased likelihood of persistent asthma in males, while prenatal phthalate exposure was associated with increased likelihood of adult asthma in males. Results suggest that prenatal exposure to prenatal BPA and phthalates affect asthma risk, particularly in males, however lung function was not adversely affected.

Aerobic degradation of bisphenol A by Pseudomonas sp. LM-1: characteristic and pathway.

Bisphenol A (BPA) has been widely used in the manufacture of polymeric materials. BPA is regarded as an endocrine disrupting chemical, posing a great threat to the public health. In this study, a bacterial strain LM-1, capable of utilizing BPA as the sole carbon and energy source under aerobic conditions, was originally isolated from an activated sludge sample. The isolate was identified as Pseudomonas sp. based on 16S rRNA gene sequence analysis. Strain LM-1 was able to completely degrade 25-100 mg/L BPA within 14-24 h, and it also exhibited high capacity for BPA degradation at a range of pH (6.0-8.0). (NH4)2SO4 and NH4NO3 were the suitable nitrogen sources for its growth and BPA biodegradation, and the BPA degradation could be accelerated when exogenous carbon sources were introduced as the co-substrates. Metal ions such as Zn2+, Cu2+, and Ni2+ could considerably suppress the growth of strain LM-1 and BPA degradation. According to the analysis of liquid chromatography coupled to Q-Exactive high resolution mass spectrometry, hydroquinone, p-hydroxybenzaldehyde, and p-hydroxybenzoate were the predominate metabolites in the BPA biodegradation and the degradation pathways were proposed. This study is important for assessment of the fate of BPA in engineered and natural systems and possibly for designing bioremediation strategies.

Exposure to Bisphenol A induces abnormal fetal heart development by promoting ferroptosis.

BACKGROUND: Bisphenol A (BPA), a common endocrine-disrupting chemical (EDC), has been revealed to be closely associated with the induction of abnormal heart development, obesity, prediabetes, and other metabolic disorders. However, the underlying mechanism of maternal BPA exposure on fetal heart development abnormalities is not clear. METHODS: To explore the adverse effects of BPA and its potential mechanism on heart development, C57BL/6 J mice and human cardiac AC-16 cells were used to conduct in vivo and in vitro studies. For the in vivo study, mice were exposed to low-dose BPA (40 mg/(kg·bw)) and high-dose BPA (120 mg/(kg·bw)) for 18 d during pregnancy. In vitro study, human cardiac AC-16 cells were exposed to BPA of various concentrations (0.01, 0.1, 1, 10, and 100 µM) for 24 h. Cell viability and ferroptosis were evaluated using 2,5-diphenyl-2 H-tetrazolium bromide (MTT), immunofluorescence staining, and western blotting. RESULTS: In BPA-treated mice, the alterations of fetal cardiac structure were observed. Increased NK2 homeobox 5(Nkx2.5) was detected in vivo with the induction of ferroptosis, revealing that BPA induced abnormal fetal heart development. Furthermore, the results showed that SLC7A11 and SLC3A2 decreased in low- and high-dose BPA-treated groups, suggesting that system Xc- mediated BPA-induced abnormal fetal heart development via inhibiting the expression of GPX4. Observing AC-16 cells confirmed that cell viability declined significantly with various concentrations of BPA. Moreover, BPA exposure suppressed GPX4 expression by inhibiting System Xc- (the decrease of SLC3A2 and SLC7A11). Collectively, system Xc- modulating cell ferroptosis might play important in abnormal fetal heart development induced by BPA exposure.

Association of urinary bisphenols with oxidative stress and inflammatory markers and their role in obesity.

Bisphenol A (BPA) and its substitutes are widely used in daily life. Animal and cell line experiments have confirmed the effects of bisphenols on oxidative stress and inflammation. However, current population evidence for the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on oxidative stress and inflammation is still sparse. Based on the National Health and Nutrition Examination Survey 2013-2016 data, our study used linear regression, weighted quantile sum model, and Bayesian kernel machine regression model to evaluate the effects of BPA, BPS, and BPF alone and in combination on oxidative stress (serum total bilirubin, and iron) and inflammation (alkaline phosphatase, C-reactive protein, γ-glutamyl transferase ferritin, neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio) markers. On this basis, the possible roles of oxidative stress and inflammation in obesity, which is associated with exposure to bisphenols (BPs), were initially explored. Based on the different covariates selected, a total of 3039 and 2258 participants were included in our study for models 1 and 2, respectively; the median age of participants was 48 years, and 48.7 % were male. Based on all models, our results showed that exposure to BPs alone or in combination was associated with downregulation of serum total bilirubin. Urinary BPF concentration was specifically associated with the neutrophil-to-lymphocyte ratio. Serum total bilirubin may play a role in the association between obesity and BP mixture exposure. Upregulation of the neutrophil-to-lymphocyte ratio was not associated with obesity. In conclusion, our study found that single or combined exposure to BPs, as measured in urine, may be associated with changes in oxidative stress and inflammatory markers, and a decrease in serum total bilirubin may play a mediating role in BP-induced obesity.

Exposure to bisphenol A alternatives bisphenol AF and fluorene-9-bisphenol induces gonadal injuries in male zebrafish.

Bisphenol A (BPA), present in many household products, can damage the male reproductive system. Accordingly, we summarized urine samples from 6921 human in National Health and Nutrition Examination Survey and found urinary BPA levels were inversely linked with blood testosterone in the children group. Currently, BPA replacements, such as fluorene-9-bisphenol (BHPF) and Bisphenol AF (BPAF), have been introduced to produce "BPA-free" products. Here we demonstrated that BPAF and BHPF could induce delayed gonadal migration and reduce the number of progenitors of germ cell lineage in zebrafish larvae. A close receptor analysis study reveals that BHPF and BPAF can strongly bind to androgen receptors, leading to the downregulation of meiosis-related genes and the overexpression of inflammatory markers. Furthermore, BPAF and BPHF can induce activation of the gonadal axis via negative feedback, leading to the hypersecretion of some upstream hormones and an increase in the expression of upstream hormone receptors. Our findings call for further research on the toxicological effects of BHPF and BPAF on human health and recommend that BPA replacements be investigated for anti-estrogenic action.

Transcriptomic analysis reveals up-regulated histone genes may play a key role in zebrafish embryo-larvae response to Bisphenol A (BPA) exposure.

Bisphenol A (BPA) can induce complex regulatory mechanisms in many aquatic organisms, and it is difficult to find a suitable analytical method to efficiently enrich key genes responding to BPA exposure. In this study, zebrafish embryo transcriptomic data were obtained from two types of different BPA exposure methods. After BPA exposure, three differential gene enrichment methods were used jointly to identify up-regulated genes or pathways in zebrafish embryo larvae. The results showed that the systemic lupus erythematosus signaling pathway was significantly enriched in all BPA exposure groups. It was also noteworthy that most of the up-regulated genes in systemic lupus erythematosus signaling were histones. In conclusion, this study suggested that autoimmunity signaling was the most common important pathway in zebrafish embryo-larvae response to different BPA exposures, and histones may play a key role in response to low-concentration BPA.

Neurotoxicity of bisphenol A exposure on Caenorhabditis elegans induced by disturbance of neurotransmitter and oxidative damage.

Bisphenol A (BPA) is putatively regarded as an environmental neurotoxicant found in everyday plastic products and materials, however, the possible neurobehavioral adverse consequences and molecular mechanisms in animals have not been clearly characterized. The nematode Caenorhabditis elegans has become a promising animal model for neurotoxicological researches. To investigate the dose-effect relationships of BPA-induced neurotoxicity effects, the locomotion behavior and developmental parameters of the nematode were determined after BPA exposure. The present data demonstrated that BPA caused neurobehavioral toxicities, including head thrashes and body bends inhibition. In addition, when C. elegans was exposed to BPA at a concentration higher than 2 µM, growth and survival rate were decreased. The serotonergic, dopaminergic and GABAergic neurons were damaged by BPA. Furthermore, lower levels of mRNA expression related to dopamine, serotonin and GABA were detected in the worms exposed to 50 µM BPA. Increased SOD-3 expression might be adaptive response to BPA exposure. Moreover, oxidative damage triggered by BPA was manifested by changes in GST-4 expression, accompany with abnormity of ATP synthesis, but not nuclear localization of DAF-16/FOXO. Finally, we showed that epigallocatechin-3-gallate partially rescued BPA-induced reactive oxygen species (ROS) production and neurobehavioral toxicity. Altogether, the neurobehavioral and developmental toxicity of BPA may be induced by neurotransmission abnormity and oxidative damage. The present data imply that oxidative stress is linked to neuronal damage and neurobehavioral harm resulting from developmental BPA exposure.

Cuscuta chinensis flavonoids reducing oxidative stress of the improve sperm damage in bisphenol A exposed mice offspring.

Bisphenol A (BPA) is a common environmental endocrine disruptor, and overexposure is a threat to male reproduction. Although studies have confirmed that BPA exposure causes a decrease in sperm quality in offspring, the dosage used, and the underlying mechanism is not clear. The purpose of this study is to investigate whether Cuscuta chinensis flavonoids (CCFs) can antagonize or alleviate BPA-induced reproductive injury by analyzing the processes associated with BPA's impairment of sperm quality. BPA and 40 mg/kg bw/day of CCFs were administered to the dams at gestation day (GD) 0.5-17.5. Testicles and serum of male mice are collected on postnatal day 56 (PND56), and spermatozoa are collected to detect relevant indicators. Our results showed that compared with the BPA group, CCFs could significantly increase the serum contents of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) in males at PND 56, as well as the transcription levels of estrogen receptor alpha (ERα), steroidogenic acute regulatory protein (StAR) and Cytochrome P450 family 11, subfamily A, and member 1 (CYP11A1). CCFs also significantly inhibit the production of reactive oxygen species (ROS), reduce oxidative stress, increase mitochondrial membrane potential, and reduce sperm apoptosis. It also has a certain regulatory effect on sperm telomere length and mitochondrial DNA copy number. These results suggest that CCFs can increase reproductive hormone and receptor levels in adult males by regulating the expression of oxidative stress correlated factors, and ultimately mitigate the negative effects of BPA on sperm quality in male mice.

TMBPF-induced neurotoxicity and oxidative stress in zebrafish larvae: impacts on central nervous system development and dopamine neurons.

Bisphenol A (BPA), a common bisphenol molecule, is well known in the environment as an endocrine disruptor. Furthermore, BPs (BPA, BPS, BPF, and BPAF) have been shown in recent years to be neurotoxic to zebrafish. Tetramethyl bisphenol F (TMBPF) has recently been introduced as a substitute for bisphenol A (BPA) in various industries, including plastics and food contact coatings. However, a growing number of studies have demonstrated that the toxicity of some BPA substitutes is similar to or even stronger than BPA, posing potential harm to human health and the environment. In this study, we used zebrafish larvae as a model to investigate the neurodevelopmental effects of TMBPF at different concentrations (0, 0.25, 0.5, 1, 2, 4 and 8 mg/L). Our results showed that exposure to TMBPF at concentrations higher than 4 mg/L for 72 h post-fertilization (hpf) resulted in zebrafish mortality, whereas exposure to 2 mg/L for 144 hpf caused deformities. Furthermore, TMBPF exposure inhibited the development of the central nervous system, motor nerves, and dopamine neurons in zebrafish. Real-time polymerase chain reaction (PCR) analysis revealed that TMBPF exposure significantly down-regulated the expression of oxidative stress-related genes (Cu/Zn-SOD, Mn-SOD, and CAT) and neurodevelopmental genes (mbp, gafp, and syn2a), while up-regulated the expression of dopamine-related genes (th1, th2, and dat). Notably, treatment with the antioxidant N-acetylcysteine (NAC) alleviated TMBPF-induced toxicity. NAC can regulate the expression of genes related to oxidative stress, neurodevelopment and dopamine development, and make the nerve development of zebrafish normal. Overall, our research suggested that TMBPF may disrupt the development of the early central nervous system and dopamine neurons, leading to abnormal motor behavior in zebrafish larvae. These results highlight the potential risks associated with the use of TMBPF in various industries and the importance to evaluate its potential risks to human health and the environment.

Prenatal exposure to bisphenol AF induced male offspring reproductive dysfunction by triggering testicular innate and adaptive immune responses.

As an emerging endocrine-disrupting component with a chemical structure related to Bisphenol A (BPA), Bisphenol AF (BPAF) has become widely distributed in the environment and human surroundings. Although numerous studies have focused on its reproductive toxicity, the impact of prenatal BPAF exposure on the reproductive system of adult male offspring, particularly testicular morphology and function, as well as the underlying mechanisms, remains largely understudied. This study found prenatal BPAF exposure at a dose of 300 µg/kg b.w. induced a 32% loss of seminal vesicle weight, a 12% reduction in the anogenital distance index (AGI), and impairments to testicular morphology, such as a reduced diameter of seminiferous tubules and thickness of the seminiferous epithelium, as well as a more than 2 - fold decrease in testosterone level, and 41% and 19% reduction of sperm count and vitality, respectively, in the 10 week-old male offsprings. Testicular RNA-Seq data showed that 334 differential expressed genes (DEGs) were primarily involved in several immunological processes, including host defense response, innate and adaptive immune response, cellular response to interferon (IFN)-ß and γ, antigen processing and presentation, regulation of T cell activation, etc. Importantly, our results revealed a pattern recognition receptor - absent in melanoma-2 (Aim2) was significantly increased in the testes of exposed males, thus triggering a testicular innate antiviral immunological response, leading to an increase of F4/80+ and CD11b+ macrophage. Subsequently, Aim2 activated the downstream signaling nuclear factor kappa-B (NF-κB), stimulated the transcription of IFN-ß and -γ, and then induced cytokine production while upregulating MHC class II molecules to activate CD4+ and CD8+ Tcells, suggesting that an adaptive immune response was also elicited. The results demonstrated that prenatal BPAF exposure could provoke innate and adaptive immunological responses in the testes of adult males through the Aim2-NF-κB-IFNs signaling pathway. Our work provided insights into understanding the reproductive toxicity caused by BPAF and clarified the possible mechanisms, which offered a potential therapeutic target and treatment strategy for BPAF exposure-induced reproductive dysfunction.

Bisphenol A interferes with lncRNA Fhadlos2 and RUNX3 association in adolescent mouse ovary.

Bisphenol A (BPA) has a number of adverse effects on the reproductive development of females. In particular, the mechanism of disruption of ovarian development in adolescent mice is still unclear. Based on transcriptome sequencing results, a differentially expressed lncRNA, Fhad1os2, was detected in the ovaries of BPA-exposed pubertal mice. In our study, the lncRNA Fhad1os2, localized in the ovarian granulosa cell cytoplasm, could regulate the proliferation of mouse ovarian granulosa cells. Mechanistically, the results of RNA pull-down experiments as well as mass spectrometry analysis showed that ERα, an interfering signaling molecule of BPA, could directly bind lncRNA Fhad1os2 and decrease the transcription of lncRNA Fhad1os2 in response to the estrogen-like effect of BPA. BPA exposure also caused abnormal lncRNA Fhad1os2 pulldown protein-related signaling pathways in the ovaries of adolescent mice. Furthermore, lncRNA Fhad1os2 interacted with RUNX3, a transcription factor related to follicle development and hormone synthesis. As a negative regulator, lncRNA Fhad1os2 transactivated the expression of Runx3, which in turn induced RUNX3 to positively regulate aromatase (Cyp19a1) expression in mouse ovarian granulosa cells and promote estrogen synthesis. In conclusion, our study indicates that BPA exposure interferes with ERα-regulated lncRNA Fhad1os2 interactions with RUNX3 in pubertal mice, affecting estrogen synthesis in mouse granulosa cells and contributing to premature ovarian maturation in pubertal mice.