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A new and highly sensitive voltammetric technique was described in this study for the concurrent detection of endocrine disruptors bisphenol A (BPA) and bisphenol AF (BPAF) based on carbon nanocages (CNCs) and copper oxide nanochains (CuONCs). The CNCs was prepared by the solvothermal method and characterized using various techniques. Utilizing the nanocomposite of CNCs and CuONCs, the voltammetric sensor demonstrated outstanding performance in detecting BPA and BPAF simultaneously with distinct oxidation peaks and increased current peaks. The voltammetric signals have linear relationships with the two bisphenols ranging from 0.500 µM to 100 µM with a detection limit of 0.16 µM for BPA and 0.14 µM for BPAF. The newly designed sensor showed reliable consistency, long-term durability and anti-interference ability, and performed well in analyzing real water samples, indicating great potential for environmental monitoring.

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As a replacement for bisphenol A (BPA), bisphenol AF (BPAF) showed stronger maternal transfer and higher fetal accumulation than BPA. Therefore, concerns should be raised about the health risks of maternal exposure to BPAF during gestation on the offspring. In this study, SD rats were exposed to BPAF (0, 50, and 100 mg/kg/day) during gestation to investigate the bioaccumulation and adverse effects in liver, spleen, and kidney tissues of the offspring at weaning period. Bioaccumulation of BPAF in these tissues with concentrations ranging from 1.56 ng/mg (in spleen of males) to 55.44 ng/mg (in liver of females) led to adverse effects at different biological levels, including increased relative weights of spleen and kidneys, histopathological damage in liver, spleen, and kidney, organ functional damage in liver, spleen, and kidney, upregulated expression of genes related to lipid metabolism (in liver), oxidative stress response (in kidney), immunity and inflammatory (in spleen). Furthermore, dysregulated metabolomics was identified in spleen, with 217 differential metabolites screened and 9 KEGG pathways significantly enriched. This study provides a comprehensive insight into the systemic toxicities of prenatal exposure to BPAF in SD rats. Given the broad applications and widespread occurrence of BPAF, its safety should be re-considered.

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Bisphenol F (BPF) and bisphenol AF (BPAF) are structural analogues of bisphenol A (BPA) that are used in the manufacture of a myriad of BPA-free products; however, there is a paucity of information regarding their developmental effects. The present study investigates the effects of BPF and BPAF on neurodevelopment and pancreatic ß-cell differentiation via altering DNA methylation and gene expression patterns using the zebrafish model. BPF and BPAF induced behavioral perturbations: increased average speed, increased maximum acceleration, increased mania time and decreased static time, in 0.3 and 1.0 µM groups in zebrafish embryos. Glucose level was significantly increased in 1.0 µM BPF (28 %); while a monotonic increase of 29 %, 55 %, and 74 % were observed in 0.1, 0.3, and 1.0 µM BPAF, respectively. Consistent with a decreased insulin mRNA level, the expression of two critical transcription factors (pdx-1 and foxa2) essential for the development and functioning of beta-cells decreased following the bisphenols exposure. In addition, embryonic exposure to BPF and BPAF upregulated the transcription of developmental genes (vegfa, wnt8a, and mstn1) and neuron-related genes (mbp, elavl3, gap43, gfap). Also, the expressions of DNA methyltransferases (dnmt1, dnmt3, dnmt4, dnmt5, dnmt6, dnmt7, and dnmt8) were significantly aberrant compared with the control group. The Bisulfite PCR results indicate increased DNA methylation at promoter regions of pdx-1 in BPF (8.2 %) and BPAF (7.6 %); α1-tubulin in BPF (5.3 %) and in BPAF (4.1 %), congruous with the increased dnmt1 and dnmt3 transcription, at early stage of zebrafish development. The present study indicates that zebrafish embryonic exposure to BPF and BPAF elicits islet dysfunction and neuron perturbations resulting in increased DNA methylation levels.

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Bisphenol A (BPA) is a synthetic chemical primarily utilized in the manufacturing of polycarbonate plastics and epoxy resins that are present in various consumer products. While the BPA impacts on female reproductive toxicity have been widely investigated, very little is currently identified about the mixed toxicity of BPA and bisphenol AF (BPAF), another common BPA derivative that is used in many industrial applications. In this study, we assessed the effect of co-exposure of BPA (30 and 50 µM) and BPAF (3 and 5 µM) on mitochondrial dysfunction in human granulosa cells (KGN cells) for 24 h. Our results exhibited that high-concentration bisphenol individual or their mixture exposure of KGN cells induced significant mitochondrial dysfunction by reducing mitochondrial mass, reducing ATP production, and damaging the mitochondrial respiratory chain. In addition, we found that the combination of BPA and BPAF significantly induced mitochondrial stress by increasing calcium levels and the production of ROS in mitochondria. Mitochondrial stress induced by BPA and BPAF was determined to be a mechanism that promoted cell apoptosis after pretreating the cells with the mitochondrial-targeted antioxidant and the calcium chelator. Our results provide novel evidence of the cytotoxicity of mixtures of different bisphenol compounds.

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Bisphenol AF (BPAF) is found in high concentrations in aquatic environments due to the increased use of thermal paper and food packaging. However, there have been relatively few toxicological studies and potential risk assessments of BPAF. In this study, the risk quotient (RQ) and hazard quotient (HQ) of BPAF were derived to present the safety standards for environmental risk management and protection in lakes, rivers, bays, and Italian regions. We applied the species sensitivity distribution (SSD) method based on the previous ecotoxicological data and the results of supplementary toxicity tests on BPAF. From the SSD curves, the hazardous concentration for 5 % of the species (HC5) values for the acute and chronic toxicity data were 464.75 µg/L and 3.59 µg/L, respectively, and the acute- and chronic-based predicted no-effect concentration were derived as 154.92 µg/L and 1.20 µg/L, respectively. The acute-based RQ (RQA)values of BPAF in all regions were negligible (RQ < 0.1). The chronic-based RQ (RQC) in the Xitang River (XR) and the Central Italy (CI) showed a considerably high ecological risk (12.77 and 1.29) and the Hangzhou Bay (0.21), the South and North Italy (0.79 and 0.27), and the Tamagawa River (0.13) had a medium ecological risk (0.1 < RQ < 1.0). However, the HQ values based on the tolerable daily intake for BPAF over all age groups in these regions was < 0.1, indicating the low health risk. Nonetheless, the result of this study indicates that BPAF contamination is serious in XR and CI, and their use and emissions require continuous monitoring.

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Recently, bisphenol AF (BPAF) as most commonly used bisphenol A analogs had the increasing higher level in the environment with unknown risks. Herein, a synchronous dual-mode sensor had been established based on differential pulse voltammetry (DPV) and electrochemiluminescence (ECL) for the detection of BPAF in pond mud. Firstly, the sensing molecularly imprinted polymer (MIP) films were prepared by electrochemical polymerization procedure with 3,4-ethoxylene dioxy thiophene (EDOT) as the functional monomer, BPAF as the template molecule and MXene as the supporting electrolyte. Due to unique characters of PEDOT and MXene, the constructed MIP films were stable and highly conductive. Meanwhile, zinc-doped bismuth sulfide quantum dots (Zn-Bi2S3 QDs) were synthesized as a nano-emitter to generate strong ECL signals in the MIP film. In the sensing process, a pulsed voltage applied to the PEDOT/MXene MIP film to generate both DPV and ECL signals for simultaneous dual-mode detection. Additionally, the liquid-liquid extraction with deep eutectic solvent (menthol: octanol 1:1) was used for the pre-concentration of the BPAF in the pond mud. Based on the sensing system, the ECL and DPV response showed the good linear relationships with the concentration of BPAF with the ranges of 0.01 µM-50 µM and 0.1 µM-50 µM and the detection limits of 0.0060 µM and 0.059 µM, respectively.

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Bisphenol A (BPA) and its analogues (BPAF, BPS) are ubiquitous environmental contaminants used as plastic additives in various daily life products, with many concerns on their role as environmental estrogens. Uterine leiomyomas (fibroids) are highly prevalent gynecologic tumors with progressive fibrosis. Fibroids are hormone-responsive and may be the target of environmental estrogens. However, the effects of BPA, BPAF, and BPS exposure on uterine fibrosis are largely unknown. Here, we evaluated fibrosis and the crucial role of TGF-beta signaling in human fibroid tumors, the profibrotic effects of BPA, BPAF or BPS in a human 3D uterine leiomyoma (ht-UtLM) in vitro model, and the long-term outcomes of BPAF exposure in rat uterus. In 3D ht-UtLM spheroids, BPA, BPAF, and BPS all promoted cell proliferation and fibrosis by increasing the production of extracellular matrices. Further mechanistic analysis showed the profibrotic effects were induced by TGF-beta signaling activation mainly through SMAD2/3 pathway and crosstalk with multiple non-SMAD pathways. Furthermore, the profibrotic effects of BPAF were supported by observation of uterine fibrosis in vivo in rats following long-term BPAF exposure. Overall, the 3D ht-UtLM spheroid can be an important model for investigating environment-induced fibrosis in uterine fibroids. BPA and its analogues can induce fibrosis via TGF-beta signaling.

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Previous studies show that bisphenol A (BPA) and its analogs induce oxidative stress and promote inflammatory response. However, the key molecules in regulating this process remain unclear. Here, we report significant inductive effects of BPA and bisphenol AF (BPAF) on a newly found long non-coding RNA linc-93.2 accompanied by oxidative stress and activation of pro-inflammatory pathways in treated fish and fish primary macrophages. Silencing linc-93.2 in fish primary macrophages in vitro or fish in vivo significantly promotes the expression of anti-oxidative stress-related genes and anti-inflammatory cytokines. This inhibition of pro-inflammatory cytokine expression, showing cell status disruption towards to M2 polarization. Followed by exposure to BPA or BPAF, silencing linc-93.2 in vitro or in vivo significantly attenuates the increased production of reactive oxygen species and malondialdehyde level aroused by bisphenol treatment, possibly owing to the enhancement of total antioxidant capacity observed in cells and tissue after linc-93.2 knockdown. RNA-sequencing further revealed regulation of nuclear factor-kappa b (NF-κB) in linc-93.2's downstream network, combining with our previous observation on the upstream regulation of linc-93.2 via NF-κB, which together suggest a critical role of linc-93.2 in promoting NF-κB positive feedback loop that may be an important molecular event initiating the immunotoxicity of bisphenols.

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BACKGROUND: Child maltreatment (CM) is correlated with suicidality risk among adolescents. Additionally, exposure to bisphenol AF (BPAF) may increase this risk. However, the combined effect of CM and BPAF exposure remains unknown and should be further investigated. METHODS: In this study, 1,475 early adolescents (mean age = 12.48 years) from the Chinese Early Adolescents Cohort were enrolled. Data were collected at three time points with an interval of 12 months between 2019 and 2021. Participants' history of CM and suicidality (including suicidal ideation and suicidal attempts) were evaluated using a self-report questionnaire. Blood samples were obtained from participants to measure serum BPAF concentrations at baseline. Group-based trajectory modeling was employed to identify different developmental trajectories of suicidality across the three waves. After adjusting for potential confounders, the association between CM and BPAF exposure on suicidal ideation and suicidal attempts was assessed using logistic regression and Poisson regression analyses. RESULTS: Participants with CM were associated with a risk of one- and two-year incident suicidality (all ps < 0.05), and BPAF levels were positively associated with two-year incident suicidal ideation (adjusted OR = 1.68, 95% CI: 1.13-2.50). Additionally, middle and high levels of BPAF exposure synergistically increase the risk for one- and two-year incident suicidal ideation among participants with CM (adjusted ORs = 2.00-3.83). Similarly, participants exposed to high-level BPAF as well as CM were at a greater risk of one- and two-year incident suicidal attempts than those with low-level BPAF exposure and no CM (adjusted incidence rate ratio [IRRs] = 2.82-4.34). Moreover, compared with participants with a low developmental trajectory of suicidality across the three waves, high BPAF exposure exhibited a significant synergistic effect on participants with CM in the persistently high suicidal ideation trajectory and the increasing suicidal attempts trajectory (all ps < 0.05). Sex subgroup analysis revealed that females were more susceptible to the synergistic effect of BPAF and CM exposure on suicidality than males. CONCLUSIONS: Environmental factors and the psychological status of individuals may synergistically increase their susceptibility to suicidality. These results offer novel insights into enhancing our understanding of suicidality among adolescents.

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Bisphenol compounds (BPA, BPS, BPAF, etc.) are one class of the most important and widespread pollutants that poses severe threat to human health and the ecological environment. Because of the presence of multiple bisphenols in environmental and food samples, it is urgent and challenging to develop a rapid and cheap technique for simultaneously detecting BPA and its analogues. In this study, a series of M-N-C (M = Cu, Mg, Ni, Co, Fe, K) single-atom nanozymes (SAzymes) were created by simulating the structure of natural enzyme molecules, which were used as novel sensing platform for the fabrication of electrochemical sensors. Through systematic screening and characterization, it was interestingly discovered that the electrochemical sensor based on Cu-N-C SAzymes exhibited the best sensing performance for bisphenols among all SAzymes, which catalyzed not only BPA like tyrosinase, but also showed excellent catalytic capacity beyond tyrosinase (tyrosinase has no catalytic activity for BPS, BPAF, etc.), and achieved potential-resolved simultaneous rapid detection of BPA, BPS and BPAF. Further structure-activity relationship and catalytic mechanism characterizations of Cu-N-C SAzymes revealed that the presence of single atom Cu was predominantly in the form of Cu+ and Cu2+, which were anchored onto graphene nanosheet support through four coordination bonds with pyridinic N and pyrrolic N and acted as highly efficient active centers for electrocatalytic oxidation of bisphenols. The developed electrochemical sensing method exhibited excellent selectivity, sensitivity, and reliability for the rapid detection of multiple bisphenols in actual samples.

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The estrogen-like effect of bisphenol A (BPA) disrupting the maintenance of functional male germ cells is associated with male sub-fertility. This study investigated toxicity of male germ cells induced by four bisphenol analogs: BPA, BPAF, BPF, and BPS. The investigation of bisphenol analogs' impact on male germ cells included assessing proliferation, apoptosis induction, and the capacity to generate reactive oxygen species (ROS) in GC-1 spermatogonia (spg) cells, specifically type B spermatogonia. Additionally, the therapeutic potential and protective effects of N-Acetyl Cysteine (NAC) and NF-κB inhibitor parthenolide was evaluated. In comparison to BPA, BPF and BPS, BPAF exhibited the most pronounced adverse effect in GC-1 spg cell proliferation. This effect was characterized by pronounced inhibition of phosphorylation of PI3K, AKT, and mTOR, along with increased release of cytochrome c and subsequent cleavages of caspase 3, caspase 7, and poly (ADP-ribose) polymerase. Both NAC and parthenolide were effective reducing cellular ROS induced by BPAF. However, only NAC demonstrated a substantial recovery in proliferation, accompanied by a significant reduction in cytochrome c release and cleaved PARP. These results suggest that NAC supplementation may play an effective therapeutic role in countering germ cell toxicity induced by environmental pollutants with robust oxidative stress-generating capacity.

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Bisphenol AF (BPAF) is a novel environmental endocrine disruptor, and is widely detected in the aquatic environment, which is a potential threat to the health of fish. In this study, male Oryzias curvinotus were exposed to environmental concentrations (0.93 and 9.33 µg/L) of BPAF for 21 days. The effects of BPAF on survival, growth, reproduction, liver and testis histology, and gene transcriptional profiles of O. curvinotus were investigated. The results showed that the survival rate of male O. curvinotus slight decrease with increasing BPAF concentration, and there was no significant effect on body length, body weight, and K-factor. BPAF (9.33 µg/L) caused significant changes in testicular structure and reduced spermatid count in O. curvinotus. Changes in transcript levels of some antioxidant-related genes in gills and liver following BPAF exposure, imply an effect of BPAF on the immune system. After BPAF exposure, chgs and vtgs were up-regulated, validating the estrogenic effect of BPAF. In the hypothalamic - pituitary - gonadal axis (HPG) results, erα, erγ and cyp19a1b were all up-regulated in the brain, and the 0.93 µg/L BPAF group was more up-regulated than the 9.33 µg/L BPAF group. In testis, BPAF significantly up-regulated the mRNA expression level of cyp17a1 and cyp11b, while significantly down-regulated mRNA expression level of cyp11a, and cyp19a1 was significantly down-regulated only in the 0.93 µg/L BPAF group. In conclusion, environmental levels of BPAF have adverse effects on the survival and reproduction of O. curvinotus, and the potential toxic effects of environmental levels of BPAF cannot be ignored.

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Fragmented data suggest that bisphenol AF (BPAF), a chemical widely used in a variety of products, might have potential impacts on the hypothalamus. Here, we employed male neonatal mice following maternal exposure to explore the effects of low-dose BPAF on hypothalamic development by RNA-sequencing. We found that maternal exposure to approximately 50 µg/(kg·day) BPAF from postanal day (PND) 0 to PND 15 altered the hypothalamic transcriptome, primarily involving the pathways and genes associated with extracellular matrix (ECM) and intercellular adhesion, neuroendocrine regulation, and neurological processes. Further RNA analysis confirmed the changes in the expression levels of concerned genes. Importantly, we further revealed that low-dose BPAF posed a stimulatory impact on pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus and induced the browning of inguinal white adipose tissue. All findings indicate that developmental exposure to low-dose BPAF could interfere with hypothalamic development and thereby lead to alterations in the metabolism. Interestingly, 5000 µg/(kg·day) BPAF caused slighter, non-significant or even inverse alterations than the low dose of 50 µg/(kg·day), displaying a dose-independent effect. Further observations suggest that the the dose-independent effects of BPAF might be associated with oxidative stress and inflammatory responses caused by the high dose. Overall, our study highlights a risk of low-dose BPAF to human neuroendocrine regulation and metabolism.

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A magnetic molecular imprinted covalent organic framework composite (MCOF-MIP) that possessed the 'dual-selectivity' of a covalent organic framework and molecular imprinted polymer (MIP) with rapid response performance was successfully prepared for the removal of bisphenol AF (BPAF) from real water and blood samples. First, the MCOF was separately synthesized using magnetic Fe3O4 as the magnetic core, 1,3,5-triaminobenzene and 2,5-dibromobenzene-1,4-diformaldehyde as precursors and a deep eutectic solvent (DES) as the solvent using a solvothermal synthesis method. The MCOF showed high crystallinity and good adsorption capacities for BPAF (107.4 mg g-1), bisphenol A (113.6 mg g-1), bisphenol S (120.0 mg g-1) and bisphenol F (82.1 mg g-1). To further improve the selectivity for BPAF, an MIP, which uses BPAF as a template, was introduced to form the MCOF-MIP. Due to the dual selectivity of MCOF and MIP, the MCOF-MIP exhibited relatively high selective adsorption capacity to BPAF (243.1 mg g-1) compared to that for the MCOF (107.4 mg g-1), while the adsorption capacities (149.7-109.4 mg g-1) for the other three compounds were not significantly improved. Furthermore, a magnetic solid-phase extraction (MSPE) method was established, and MSPE parameters such as adsorbent dosage, adsorption time, desorption solvent and desorption time were optimized. Combined with high-performance liquid chromatography with diode-array detection (HPLC-DAD) analysis, a rapid and sensitive method was developed to detect BPAF, which showed good linearity (r > 0.9969) ranging from 0.1 to 400 µg mL-1. Low limits of detection (0.04 µg mL-1, S/N = 3) and quantitation (0.1 µg mL-1, S/N = 10) and good precision with low relative SDs (<1.2 % for intra-day and <1.1 % for inter-day) were also obtained. Finally, MSPE coupled with HPLC-DAD was employed for the analysis of BPAF in water and blood samples, and the recoveries of BPAF were satisfactory (91.1-112.6 %).

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Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28-day multi-endpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF-treated groups (0.5, 5, and 50 µg/kg·bw/d), BPA group (10 µg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high-dose recovery group (BPAF-HR), oil recovery group (oil-R), ENU recovery group (ENU-R), and PBS recovery group (PBS-R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood-testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA.

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Bisphenol AF (BPAF) is extensively used in industrial production as an emerging substitute for the earlier-used bisphenol A (BPA). Studies have found that BPAF had stronger estrogenic activities than BPA. However, the effects of BPAF on the luteal function of pregnancy and its possible mechanisms are largely unknown. In this study, pregnant mice were orally administered 3.0 and 30 mg/kg/day of BPAF from gestational day (GD) 1 to 8, and samples were collected on GD 8 and GD 19. Results showed that maternal exposure to BPAF impaired embryo implantation and reduced ovarian weight, and interfered with steroid hormone secretion, and decreased the numbers and areas of corpus luteum. BPAF treatment significantly down-regulated expression levels of ovarian Star, Cyp11a, Hsd3b1, and Cyp19a1 mRNA and CYP19a1 and ERα proteins. BPAF also disrupted markers of redox/inflammation key, including silent information regulator of transcript-1 (SIRT-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-B (NF-ĸB) expressions along with reduced ovarian antioxidant (CAT and SOD) capacity, enhanced oxidant (H2O2 and MDA) and inflammatory factor (Il6 and Tnfa) activities. Furthermore, BPAF exposure inhibited macrophages with a pro-angiogenic phenotype that specifically expressed TIE-2, accompanied by inhibition of angiogenic factors (HIF1a, VEGFA, and Angpt1) and promotion of anti-angiogenic factor Ang-2 to suppress luteal angiogenesis. In addition, BPAF administration also induced luteolysis and apoptosis by up-regulation of COX-2, BAX/BCL-2, and Cleaved-Caspase-3 protein. Collectively, our current data demonstrated that gestational exposure to BPAF caused luteal endocrine disorder by altering ovarian SIRT-1/Nrf2/NF-kB expressions and macrophage proangiogenic function in mice.

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Bisphenol AF (BPAF) is a newly identified contaminant in the environment that has been linked to impairment of the male reproductive system. However, only a few studies have systematically studied the mechanisms underlying BPAF-induced toxicity in testicular Sertoli cells. Hence, this study primarily aims to explore the toxic mechanism of BPAF on the porcine Sertoli cell line (ST cells). The effects of various concentrations of BPAF on ST cell viability and cytotoxicity were evaluated using the Counting Kit-8 (CCK-8) assay. The results demonstrated that exposure to a high concentration of BPAF (above 50 µM) significantly inhibited ST cell viability due to marked cytotoxicity. Flow cytometry analysis further confirmed that BPAF facilitated apoptosis and induced cell cycle arrest in the G2/M phase. Moreover, BPAF exposure upregulated the expression of pro-apoptotic markers BAD and BAX while downregulating anti-apoptotic and cell proliferation markers BCL-2, PCNA, CDK2, and CDK4. BPAF exposure also resulted in elevated intracellular levels of reactive oxygen species (ROS) and malondialdehyde (MDA), alongside reduced activities of the antioxidants glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Furthermore, the ROS scavenger N-acetyl-L-cysteine (NAC) effectively blocked BPAF-triggered apoptosis and cell cycle arrest. Therefore, this study suggests that BPAF induces apoptosis and cell cycle arrest in ST cells by activating ROS-mediated pathways. These findings enhance our understanding of BPAF's role in male reproductive toxicity and provide a foundation for future toxicological assessments.

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Bisphenol AF (BPAF) represents a common environmental estrogenic compound renowned for its capacity to induce endocrine disruptions. Notably, BPAF exhibits an enhanced binding affinity to estrogen receptors, which may have more potent estrogenic activity compared with its precursor bisphenol A (BPA). Notwithstanding, the existing studies on BPAF-induced prostate toxicity remain limited, with related toxicological research residing in the preliminary stage. Our previous studies have confirmed the role of BPAF in the induction of ventral prostatic hyperplasia, but its role in the dorsal lobe is not clear. In this study, BPAF (10, 90 µg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg), were administered intragastrically in rats for four weeks. Through comprehensive anatomical and pathological observations, as well as the assessment of PCNA over-expression, we asserted that BPAF at lower doses may foster dorsal prostatic hyperplasia in rats. The results of IHC and ELISA indicated that BPAF induced hyperplastic responses in the dorsal lobe of the prostate by interfering with a series of biomarkers in NF-κB signaling pathways, containing NF-κB p65, COX-2, TNF-α, and EGFR. These findings confirm the toxic effect of BPAF on prostate health and emphasize the potential corresponding mechanisms.

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BACKGROUND: Diabetes mellitus (DM) is one of the largest global health emergencies of the 21st century. In recent years, its connection with environmental pollutants, such as bisphenol A (BPA), has been demonstrated; consequently, new structurally similar molecules are used to replace BPA in the plastics industry (BPS, BPF and BPAF). AIM: To carry out a systematic review to allow coherent evaluation of the state of the art. Subsequently, a meta-analysis was performed to unify the existing quantitative data. METHODS: Firstly, a systematic review was carried out, using the terms "(bisphenol) AND (Diabetes OR Hyperglycemia)", to maximize the number of results. Subsequently, three authors analyzed the set of articles. Finally, a meta-analysis was performed for each BP, using RevMan software. In addition, funnel plots were developed to study publication bias. RESULTS: The systematic analysis of the literature revealed 13 recent articles (2017-2023) related to the study paradigm. The qualitative analysis showed interesting data linking diabetes to the three most widely used substitute BPs in the industry: BPS, BPF and BPAF. Finally, the meta-analysis determined a positive relationship with BPS, BPF and BPAF, which was only statistically significant with BPS. CONCLUSION: There is a need to apply the precautionary principle, regulating the use of new BPs. Therefore, replacing BPA with BPS, BPF or BPAF is unlikely to protect the population from potential health risks, such as DM.

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Bisphenol AF (BPAF) is an endocrine disruptor, and human exposure to these chemicals is growing in industrialized nations. BPAF has been demonstrated in studies to have toxic effects on reproductive health. This study examined the effects of oral exposure to BPAF on the reproductive system and the protective effects of carvacrol in rats. From 32 Wistar albino rats, four separate groups were set up for this purpose. Carvacrol 75 mg/kg and BPAF 200 mg/kg were administered by oral gavage method. Rat sperm parameters and serum testosterone levels were measured after 28 days of administration. The study looked at the MDA in the testis tissues, as well as CAT, GPx, and GSH as antioxidants parameters, NF-κB and TNF-α as inflammatory markers, caspase-3 and Bcl-2 as apoptosis parameters, and PCNA as cell proliferation markers. In addition, testis tissues underwent histological evaluation. As a result, in rats exposed to only BPAF, sperm counts declined, testosterone levels reduced, oxidative stress, inflammation, and apoptosis increased, and cell proliferation decreased. Furthermore, severe disruptions in tissue architecture and decreased spermatogenesis were reported. In contrast, sperm parameters improved, testosterone levels increased, oxidative stress and inflammation decreased, and apoptosis was prevented in the carvacrol-treated group compared to the BPAF-only group. It was also found that spermatogenesis was maintained, and structural abnormalities in testicular tissue were mostly avoided with an increase in PCNA expression. According to the findings, despite BPAF-induced testicular and reproductive toxicity, carvacrol had therapeutic potential due to its anti-inflammatory, antioxidant, cell proliferation-increasing, and anti-apoptotic activities.