Bisphenol F (BPF) is one of the main substitutes for Bisphenol A (BPA) and is widely used in the manufacture of household products. In addition, BPF threatens human health through environmental pollution and the food chain. However, the hepatotoxicity of BPF and its effects on glucose and lipid metabolism remain unclear. This study used male SD rats as an animal model to investigate the hepatotoxicity of BPF and its effects on glucose and lipid metabolism. The results of the HE staining, serum and liver biochemical indicators show that BPF can damage the basic structure of the liver, cause liver dysfunction and lead to disorders of liver glucose metabolism and lipid metabolism. Furthermore, we conducted metabolomics and proteomics analyses on the livers of the BPF exposed group at 100 mg/kg/d in comparison with the control group. The results indicated that BPF exposure had a significant effect on liver metabolism. Combined with biological analysis and the validation of changes in genes and proteins related to glucose and lipid metabolism in the liver, it was elucidated that BPF can promote fatty acid oxidation and inhibit fatty acid synthesis through the AMPK and PPAR signaling pathways, leading to a reduction in fatty acids. Furthermore, it has been demonstrated that BPF can promote glycogen synthesis and gluconeogenesis via the AKT pathway, which can result in disorders of glucose metabolism.

Currently, there is limited information regarding the presence of chemicals in female underwear and the potential risks involved. This study investigated the levels of ten bisphenols in brassieres and briefs made in China, revealing total concentrations ranging from 13.9 to 52,967 ng/g. Bisphenol S (BPS), bisphenol F (BPF), and bisphenol A (BPA) made up a median of 53.2 %, 24.4 %, and 22.2 % of the total concentrations, respectively. The concentrations of bisphenols were significantly higher in darker samples compared to most other colors. When compared to previous reports on other textiles, this study found similar levels of BPA but higher concentrations of BPF and BPS. Furthermore, the median migration rates of BPF (39.1 %) and BPS (25.2 %) in artificial sweat were significantly greater than that of BPA (6.58 %), leading to higher exposure levels for BPF and BPS. The estimated non-carcinogenic risks associated with the three primary bisphenols in the underwear were deemed acceptable. However, the estimated exposure to BPS and BPF from this source represented about 2.53-12.0 % and 11.8-38.2 % of total human exposure, respectively, suggesting that the contamination of these chemicals in underwear is a concern that should not be overlooked.

Bisphenol A (BPA) and its substitute, Bisphenol S (BPS) are typical endocrine-disrupting chemicals used in plastics, but their cancer-promoting effect has remained controversial. Here, we investigated the effects of environmentally relevant doses of BPA/BPS exposure on the tumor microenvironment (TME) in ovarian cancer. BPA exposure levels was exhibiting a declining trend and BPS showing an ascending trend in the female population by analyzing the NHANES data (2013-2016). Low doses of BPA/BPS both significantly promoted the migration and invasion of ovarian cancer cells in a dose-dependent manner by activating the Wnt/β-catenin signaling pathway, thereby facilitating the SPP1 gene transcription. Notably, low-dose BPA/BPS exposure stimulated ovarian cancer cells to secrete OPN protein (coded by the SPP1 gene), subsequently inducing the transformation of fibroblasts into cancer-associated fibroblasts (CAFs), which could reshape the TME of ovarian cancer. Two in-vivo experiments established with nude mice and SPP1-/- mice respectively, both confirmed that low-dose BPA/BPS exposure increased the incidence of tumor metastasis accompanied by CAF infiltration, while administration of OPN-neutralizing antibodies effectively blocked these effects. Our results indicated that exposure to either BPA or its substitute BPS could promote the release of secreted protein OPN via the β-catenin/SPP1 axis, ultimately modulating the TME and enhancing the progression of ovarian cancer, providing new evidence and potential intervention strategies for the toxicological assessment and management of bisphenols.

Bisphenol analogues (BPs) are widely used as additives in a variety of products, including the components of electronic waste (e-waste). However, limited research has been conducted to evaluate the health burden of BPs exposure from e-waste recycling, particularly among frontline workers in developed regions. This study aimed to address this gap by analyzing urinary BPs and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, from 101 e-waste workers and 100 office workers in Hong Kong collected from 06/2021 to 09/2022. E-waste workers had significantly higher overall BPs concentrations than office workers (3.476 vs. 1.816 μg/L), with notable elevations in BPA, BPP, and BPZ. Male participants (3.118 μg/L) and e-waste workers involved in dismantling or repairing e-waste (4.245 μg/L) exhibited higher BPs burdens than the females (1.849 μg/L) and workers with other job designations (1.822 μg/L), respectively. Although the estimated daily intake (EDI) for BPA was below the recommended safety threshold, e-waste workers had higher EDIs for almost all BPs than office workers. BPA was the predominant analogue in e-waste and office workers (80.74 % and 75.94 %), and correlated with other BPs in e-waste workers, indicating its pervasive use in e-waste products. Exposure to BPs, both individually and as a mixture, was significantly associated with increased 8-OHdG levels, with stronger associations among female participants and the e-waste workers. The above findings suggest that e-waste workers in Hong Kong had higher BPs exposure from e-waste recycling and carried the associated health risks, with females showing greater sensitivity to BPs.

In utero exposures to estrogenic endocrine disrupting compounds (EDCs) can increase breast cancer risk in adulthood. It has previously been shown that the estrogenic plasticizer bisphenol A (BPA) alters development of the mammary gland and increases both mammary gland stiffness and tumor susceptibility in rodent models following in utero exposure. Because of its endocrine disrupting properties, BPA has been substituted with structural analogues with varying abilities to activate estrogen receptor alpha (ERα). However, the impact of in utero exposure to many of these analogues is unknown. In the present study, we aimed to analyze the impact of bisphenol analogues on collagen deposition and mammary gland stiffness and characterize mammary epithelial development following exposure to these compounds. With the exception of bisphenol S, all analogues significantly increased mammary gland stiffness at a 25µg/kg body weight dose in a manner that correlated to estrogenic activity. In contrast, significant effects on epithelial development endpoints were limited and did not follow a clear pattern. These results add to the growing literature on the hazard of bisphenol analogues and support the idea that these compounds promote abnormal mammary gland development. Furthermore, these data support a model that bisphenol compounds induce a microenvironment that may promote breast cancer development in an estrogen-dependent manner.

This study examines how bisphenol A (BPA) and elevated temperature (30 °C) affect growth, reproduction, oxidative stress, and lipid metabolism in the marine rotifer Brachionus plicatilis. We found that 30 °C alone increased reproductive output but shortened lifespan, whereas 30 °C and exposure to BPA reversed reproductive gains and restored lifespan to 25 °C control levels. Reactive oxygen species levels, as well as superoxide dismutase and catalase activities, were highest at 30 °C plus BPA exposure, indicating synergistic oxidative stress. Analysis of the single-exon FASN gene in B. plicatilis, B. rotundiformis, and B. koreanus showed two NADB_Rossmann domains and conserved fatty acid synthesis sites, although B. plicatilis displayed unique loop and interdomain variations. Expression of FASN was elevated at 30 °C but reverted to near-control levels at 30 °C plus BPA, whereas FABP, MGAT, and DGAT were consistently upregulated. These results reveal how BPA and temperature interact to modulate survival, lipid metabolism, and potential structural adaptations in B. plicatilis.

Developing human fetuses may be exposed to the chemical compound bisphenol A (BPA), and retinoic acid (RA) has been detected at low levels in water sources. RA signaling regulates key developmental genes and is essential for organ development, including the brain. We previously reported that RA/BPA coexposure of mouse embryonic stem cells potentiates RA signaling, which warrants further investigation.

This study was undertaken in human induced pluripotent stem cells (iPSCs) and zebrafish embryos to investigate whether coexposure to BPA and exogenous RA could potentiate HOX gene expression and exert pleiotropic effects on RA signaling.

Human iPSCs and zebrafish embryos were exposed to exogenous RA (0, 7.5, 10, 12.5, 100, 200 or 500  nM ) or BPA (20 μ M ) alone or coexposed to BPA (2  nM - 20 μ M ) and exogenous RA (7.5 - 100  nM ). Postexposure changes in HOX genes were assessed by quantitative polymerase chain reaction and/or transcriptome analyses. RA receptor antagonists were used to identify the receptor responsible for signaling. In zebrafish, spatial expression of fgf8a and hoxb1a was evaluated by whole-mount in situ hybridization. Mauthner cell and craniofacial cartilage anomalies were studied by immunostaining and Alcian blue staining, respectively. Transcriptome was compared between iPSCs and zebrafish to identify alterations of common biological processes. Gradient curves of RA signal were calculated to simulate the effects of exogenous RA and BPA in zebrafish.

In both iPSCs and zebrafish, RA/BPA coexposure had higher expression of 3' HOX genes in comparison with RA alone; BPA alone had no effect. Addition of RA receptor antagonists abolished these changes. In zebrafish, RA/BPA coexposure, in comparison with RA alone, resulted in a significant rostral shift in hoxb1a expression and increased rate of anomalies in Mauthner cells and craniofacial cartilage. Transcriptome comparison and correlations between the experimental results and gradient curve simulations strengthened these observations.

Our findings suggest a mechanistic link between chemical exposure and neurodevelopmental impairments and demonstrate involvement of exogenous RA signaling in endocrine disruption. Further investigation is needed to explore why BPA alone did not affect endogenous RA signaling, whereas exogenous RA signaling was potentiated with RA/BPA coexposure. https://doi.org/10.1289/EHP15574.

Breast cancer (BC) is one of the most common types of cancer and is caused by the complex interplay of genetic and environmental factors, such as an unhealthy lifestyle, family history of illness, reproductive factors, and ageing. However, increasing evidence has revealed that manufactured organic pollutants such as bisphenols are closely related to BC. Bisphenols exposure can promote the progression of BC through multiple complicated and variable molecular mechanisms. Reanalysis of existing data on this topic may reveal molecular markers with clinical value. In this study, we identified four key genes [keratin 14 (KRT14), keratin 5 (KRT5), acyl-CoA synthetase long chain family member 1 (ACSL1) and matrix metallopeptidase 1 (MMP1)] related to both bisphenols exposure and BC by employing the Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas Cervical Cancer (TCGA-CESC) dataset; notably, KRT14 expression exhibited the most significant difference between tumour and normal tissues. Further analysis of the functions and biological processes associated with KRT14 and related regulatory molecules revealed that bisphenols exposure induces BC-promoting characteristics and aggressive behaviour-related signaling pathways, such as the steroid biosynthesis, Forkhead box (FOXO) and prolactin signaling pathways. To confirm the expression and biological effects of KRT14, we conducted relevant experiments. In vitro studies revealed that bisphenols such as bisphenol A (BPA) exposure significantly affected the proliferation, migration, and invasion of MCF-7 cells by inhibiting KRT14 expression. Similarly, we also observed a decrease in KRT14 expression in BPA induced abnormal breast tissue in mice. In summary, our study revealed potential genes and pathways associated with bisphenols exposure in BC.

Neurological disorders are commonly accompanied by inflammation of the brain, which can be triggered by oxidative stress and cell damage caused by hazardous environmental substances. The ubiquitous harmful chemical bisphenol A (BPA) has been linked to several neuropsychiatric disorders and is thought to contribute to oxidative damage. This study explored the mechanisms underlying the effects of BPA on neurological health. Diosmin (DM) is a natural flavonoid (C28H32O15) found in various plants, including citrus fruits and it possess various pharmacological activities. This study investigated the neuroprotective effects of DM on BPA-induced neuroinflammation in zebrafish larvae, suggesting its potential therapeutic uses. Developmental toxicity, including mortality, hatching rate, and heart rate, was evaluated to determine DM toxicity. Oxidative stress biomarkers such as reactive oxygen species (ROS), superoxide anions (O-2), lipid peroxidation (LPO), and nitric oxide (NO) were quantified using colorimetric assays in the head region of the larvae. Antioxidant enzyme activities were measured to assess the impact of DM on antioxidant defences. Neuroinflammation was evaluated by analysing pro-inflammatory markers using RT-qPCR, and motor neuron function was assessed using acetylcholinesterase (AChE) activity and behavioural assays. The findings indicate that exposure to DM prevents neurotoxicity induced by BPA by increasing antioxidant defence enzymes and reducing the levels of ROS, O2-, LPO, and NO in the head region of zebrafish larvae. Furthermore, DM enhanced motor neuron function by increasing AChE activity and decreasing neuroinflammation by reducing the levels of pro-inflammatory markers influenced by BPA. This study suggests that DM offers neuroprotection against BPA-induced oxidative damage and neuroinflammation, thereby paving the way for the development of new treatment options for neurological disorders.

Bisphenol A (BPA) and its analogues disrupt endocrine functions, adversely impacting oocyte meiosis, maturation, and granulosa cell (GC) steroidogenesis.

To identify clinical factors, particularly adiposity and age, influencing ovarian cell sensitivity to bisphenol (BP) exposure.

This study analyzed a cohort of 368 women undergoing assisted reproductive technology (ART) from 2019 to 2023. Four BPs (BPA, BPS, BPF, and BPAF) were quantified, and ART outcomes (eg, oocyte count, embryo quality, and pregnancy rates) were assessed using regression models. GCs from 156 patients were cultured and exposed to BPS for 48 hours to evaluate progesterone and estradiol secretion based on clinical parameters.

BPS and BPA were the most prevalent BPs in follicular fluid. BP exposure was associated with reduced fertilization rates (P = .05). Obesity tended to lower live birth rates (P = .08) but did not affect embryo development or implantation. Age significantly impacted embryo quantity (P < .001) and quality (P = .03). GC progesterone secretion was correlated with donor age after exposure to 1 µM and 10 µM BPS (P = .03 for both). GCs from younger women appeared more sensitive to BPS.

Although obesity did not affect embryonic development, its association with reduced live birth rates suggests a suboptimal environment for implantation and/or fetal development. Age was linked to lower antral follicle count, pregnancy rates, and live birth rates. Younger women's GCs may exhibit heightened sensitivity to BPS exposure, warranting further investigation.

The objective of this work is to investigate for the first time the contamination of raw wool with endocrine disruptor compounds - bisphenol A (BPA) and parabens (PBs), as well as to conduct the first biomonitoring study on long-term sheep exposure to these substances. The levels of BPA, methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP) and butylparaben (BuP) were evaluated in wool samples (n = 100) from Kyrgyzstan and Poland using liquid chromatography-tandem mass spectrometry method. The highest levels were noted for BPA (range: 46.9-502 ng/g, mean 132 ± 70.5 ng/g) and MeP (range: 3.4 ng/g-71.1 ng/g, mean 19.9 ± 13.8 ng/g). Lower levels were found for EtP (range: Collapse

High concentrations of bisphenol A (BPA), a typical endocrine disruptor, have been widely found in rivers and oceans due to its extensive use in polymer production. Direct exposure to BPA in the aquatic environment is known to have toxic effects including their immune responses, neuroendocrine and reproductive systems and development on aquatic organisms. BPA has various adverse effects associated with the lipid metabolism of fish. However, there are limited studies on the specific mechanisms on sex-dependent differences in hepatic lipid metabolism in BPA-exposed fish. Therefore, we performed comparative lipid profiling by UPLC-MS/MS and metabolite profiling by GC-MS/MS in male and female zebrafish livers during uptake and depuration of BPA. BPA exposure led to similar changes in various hepatic lipids in male and female zebrafish, but several lipids including triacylglycerols were affected differently in a sex- and exposure duration-dependent manner. There were also sex-dependent responses of hepatic metabolites such as GABA, alanine, glucose, sarcosine, and allantoin, consistent with the trends in changes in lipids in response to BPA exposure in male and female zebrafish. Overall, our study identified sex-dependent differences in specific lipids and metabolites in the liver of zebrafish exposed to BPA. These findings might provide a novel reference for understanding the metabolic toxic effects of BPA and the pathways involved in these effects in aquatic organisms.

Bisphenol A (BPA) is an organic micropollutant detected in various environments, from urban to remote areas, including Arctic snow. As a known endocrine disruptor, it is essential to investigate its environmental fate and potential impact on ecosystems. Previous studies have explored BPA photodegradation and its transformation products in different aqueous environments (freshwater, seawater, and ice), by using photosensitizers to trigger specific reactions. However, there is still a significant gap in understanding the photodegradation processes in snow, which, although similar to ice, has distinct chemical and physical characteristics. In this work, we investigated the direct and indirect photodegradation of BPA in artificial snow and identified its degradation products through HPLC-HRMS. Nitrite and benzophenone-4-carboxylate, the latter used as a surrogate of chromophoric dissolved organic matter, induced significant BPA photodegradation under UVA irradiation. The photoproducts found in snow were partly similar to those previously observed in liquid water and ice. Their toxicity towards aquatic organisms was predicted with ECOSAR software as well. Finally, BPA photolysis and formation of photoproducts were investigated in two Alpine snow samples collected above and below the tree line, with a different organic matter content. Oxidation and nitration products of BPA were detected in these samples, suggesting that BPA photodegradation may indeed occur in natural snow. It was also noted that the aquatic toxicity of several identified photoproducts would be similar to that of BPA, but others may be even more toxic than the parent contaminant.

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is widely used in polymers, plasticizers, and food packaging, raising significant concerns for human health. Growing evidence links BPA exposure to cardiovascular diseases, including diabetic cardiomyopathy (DCM), a severe complication of diabetes characterized by myocardial dysfunction. This study employs an integrative approach combining network toxicology and molecular docking to elucidate the molecular mechanisms underlying BPA-induced DCM. Using computational tools such as ADMETlab2.0, ProTox3.0, GeneCards, OMIM, Swiss Target Prediction, and ChEMBL databases, we systematically predicted BPA's potential to induce DCM and constructed comprehensive disease and BPA target libraries. Venn diagram analysis identified 93 potential targets associated with BPA-induced DCM, and a robust BPA regulatory network was established using Cytoscape. Functional enrichment analyses revealed significant involvement of oxidative stress, insulin signaling, and metabolic pathways in BPA toxicity. Molecular docking simulations demonstrated stable binding interactions between BPA and core targets (INS, AKT1, PPARG, STAT3, PPARA, MMP9), with binding energies ranging from -5.3 to -7.5 kcal/mol. Our findings indicate that BPA may induce DCM through key genes and pathways, including cGMP-PKG signaling pathway, insulin signaling pathway, AMPK signaling pathway, and HIF-1 signaling pathway. This study provides a novel theoretical framework for understanding the molecular pathogenesis of BPA-induced DCM and highlights the potential of network toxicology in identifying toxic pathways for uncharacterized environmental compounds. These insights offer potential targets for preventive and therapeutic strategies against BPA-associated cardiovascular complications.

Bisphenol A (BPA) is a high-production-volume industrial chemical and component of commonly used plastic products. However, it is also an endocrine-disrupting chemical that can negatively affect human health. It is not yet known whether it is associated with the development of epithelial ovarian cancer (EOC), a severe and highly fatal human disease. Therefore, the purpose of this study was to determine the concentrations of BPA in the urine of women with EOC or epithelial borderline ovarian tumors (EBOTs) using gas chromatography tandem mass spectrometry (GC-MS/MS) and find their possible associations with kidney function at the molecular level, urine and blood biochemical parameters related to metabolism, anti-Müllerian hormone (AMH) (a marker of ovarian reserve/fertility), and lifestyle habits determined via a questionnaire in comparison to healthy controls. The results suggest that the unadjusted or urine-specific-gravity-adjusted BPA levels were significantly increased in women with EOC/EBOT. The unadjusted BPA was significantly positively associated with urinary creatinine (p = 0.007) in all women with EOC/EBOT after adjustment for age, body mass index, and pregnancy using multiple linear regression analysis. This may be related to kidney injury. However, no association was found between urinary BPA and serum AMH levels in women. Women with ovarian malignancies were more exposed to plastic products for storing foods and drinks. Some lifestyle habits, including refilling plastic bottles, correlate with higher urinary BPA levels across the entire cohort of women. When considering EOC or EBOT, it is necessary to consider the potential higher exposure of women to BPA, as reflected in their urine and lifestyle habits.

Bisphenol A (BPA) has emerged as a typical contaminant which can induce various adverse effects on human health and environment. BPA exposure and the corresponding human responses vary across different regions and populations. China is one of the largest producers and consumers of BPA, but the exposure profile of BPA in Chinese population is poorly understood. Physiologically-based pharmacokinetic (PBPK) models are emerging as useful tools to predict the internal exposure profiles of chemicals. Herein, the present study was aimed to predict the exposure profile of BPA in Chinese population by PBPK modeling using external BPA exposure data. A PBPK model specific for oral BPA exposure in Chinese population was established using interspecies and route-to-route extrapolations using pharmacokinetic data from intravenous BPA exposure studies in monkeys. This model was refined and validated using the data concerning BPA physicochemical properties and pharmacokinetic (absorption, distribution, metabolism, and excretion) data from existing literatures. Afterward, this model was applied to simulate the internal exposure profile of BPA in Chinese population by integrating external exposure data from the Fifth China Total Diet Survey with physiological parameters specific to Chinese population. Parameter sensitivity and modeling uncertainty were analyzed. Based on the simulated BPA internal profile, human equivalent dose factors (HEDF) were calculated. Our results provide an important basis for assessment of the potential risk of BPA exposure in Chinese population and an essential reference for determination of the safe margin limits for BPA in China.

We conducted pioneering research evaluating Akkermansia muciniphila and Faecalibacterium prausnitzii as next-generation probiotics (NGPs) for removing bisphenol A (BPA) analogues, such as bisphenol F (BPF) and tetramethylbisphenol F (TMBPF). Chronic exposure to these under-researched compounds through contaminated food poses a risk to health by promoting gut microbiota imbalances and inflammation. In our experiments, pasteurized F. prausnitzii removed up to ∼87 % of TMBPF after 48 h (from 9,976 ± 0,790 μg/mL to 1,350 ± 0,330 μg/mL μg/mL, p < 0.0001) through bioadsorption. Meanwhile, A. muciniphila achieved ∼48 % removal of BPF (from 10,33 ± 0,96 μg/mL to 5,33 ± 0,62 μg/mL, p < 0.0001) via biotransformation also after 48 h. Bioadsorption and biotransformation mechanisms were compared across conditions, with significant differences (p < 0.01) observed only for A. muciniphila with BPF and F. prausnitzii with TMBPF after 48 h. No cytotoxic effects of raw bisphenols were seen in Caco-2 cells, although the post-fermentation supernatant from A. muciniphila reduced cell viability to 68 % (p < 0.001). Notably, TMBPF showed no estrogenic activity, while BPF exhibited strong estrogenicity, which decreased following incubation with both strains. These findings confirm both NGPs reduce bisphenol concentrations, supporting their use in detoxification and functional food development. Implementing NGP-based strategies in food production and supplementation could lower human exposure to harmful bisphenols. This approach underscores the promise of advanced probiotics in mitigating foodborne chemical risks and aligns with evolving regulations and public health efforts to protect consumers.

This review's main purpose is to draw attention to the possible influence of widely used bisphenols on the inflammatory process. Bisphenols are endocrine-disrupting chemicals that are produced worldwide in great quantities. From this point of view, it is very important to clarify their influence on innate immune reactions, which protect the integrity of the body against the action of various pathogens on a daily basis. The inflammation process consists of several key factors that are produced at different levels of this reaction. Each of these levels can be affected by endocrine disruptors, from the point of view of modifying either the immune system cells that intervene in this process or the way in which they produce inflammatory mediators. The development of new recommendations for the use of bisphenols is a complex issue given their influence on inflammatory processes. Because the immune system and immune response are so intricate, bisphenols may pose more risk to humans than is presently recognized. This paper discusses the classification of bisphenols, the fundamental mechanism of inflammation, the characterization of inflammatory mediators, and the current knowledge of the molecular mechanisms behind the impact of bisphenols on the inflammatory response.

Urinary incontinence (UI) significantly impacts the quality of life and psychological well-being of female patients. Although emerging evidence suggests potential links between endocrine-disrupting chemicals and pelvic floor disorders, previous studies on the association between bisphenol A (BPA) exposure and UI in women have yielded inconsistent results. This study aimed to examine this potential association using data from the 2015-2016 National Health and Nutrition Examination Survey (NHANES) (n = 467). Through multiple logistic regression analysis with three adjustment models: Model 1 (crude), Model 2 (adjusted for socio-demographic factors: age, race/ethnicity, education, marital status, and poverty ratio), and Model 3 (further adjusted for BMI, hypertension, diabetes, alcohol/smoking status, and delivery history), we assessed BPA exposure categorized into quartiles. No significant associations were observed between BPA exposure and either stress urinary incontinence (SUI) or mixed urinary incontinence (MUI) across all models (P > 0.05). However, participants in the highest BPA quartile (> 7.6 ng/mg creatinine) exhibited a significantly increased risk of urge urinary incontinence (UUI) in Model 1 (OR = 2.01, 95% CI [1.12-3.63]), Model 2 (OR = 2.04, 95% CI [1.08-3.85]), and Model 3 (OR = 2.48, 95% CI [1.18-5.20]). This study has several limitations, including its cross-sectional design, reliance on self-reported UI outcomes, single measurement of urinary BPA, and potential residual confounding from unmeasured factors. While these findings suggest that environmental BPA exposure may contribute to UUI risk in women, future longitudinal studies with repeated biomarker measurements and objective UI assessments are needed to confirm these observations and explore potential mechanisms. If validated, reducing BPA exposure through public health interventions could emerge as a novel preventive strategy for UUI.

Bisphenol A (BPA) is an endocrine-disrupting chemical that is increasingly becoming a vital factor in public health due to its ubiquity and toxicity. BPA is associated with male infertility via the disrupted function of Leydig and Sertoli cells. Despite extensive research, the current understanding of the specific pathological concentrations and the mechanisms following BPA exposure still remain questionable. Therefore, we investigated the susceptibilities and underlying mechanisms in Leydig and Sertoli cells following treatment with various BPA doses (0.0001-100 µM in a 10-fold serial dilution). Our results showed that the lowest BPA levels (10-4 μM) decreased mitochondrial membrane potential and ATP levels. In contrast, ROS levels were increased at high BPA levels regardless of exposure time (24 or 48 h) in both cell types. Mitochondrial-mediated apoptosis was identified along with increased ROS levels and abnormal mitochondrial dynamics, but both cell types showed different susceptibility to BPA toxicity. Subsequently, BPA had detrimental impacts on the mRNA expression levels of steroidogenic enzymes and testosterone synthesis in Leydig cells and reduced anchoring junction proteins in Sertoli cells. Consequently, our results demonstrated that both cells were affected via estrogen receptor alpha. However, protein kinase A was oppositely expressed following BPA exposure in each cell type. Therefore, it is plausible to suggest that each cell has distinct sensitivities and mechanisms in response to BPA.

This research was designed to study the carcinogenic mechanisms of BPA on ovarian epithelial cells. For four months, mice were treated with low (LD, 1 mg/kg) and high (HD, 5 mg/kg of body weight) doses of BPA on alternate days through oral gavage; the control group was given corn oil through gavaging during 4 months. The histopathological data suggest that repeated BPA administration induces a borderline epithelial neoplasm with altered epithelial morphology with branching papillae. Various epithelial cells (ECs) in ovaries were identified by flow cytometry based on anti-mouse CD74 and podoplanin (PDPL) receptors expression. Three different populations of ovarian epithelial cells were identified: epithelial cells type 1 (PDPL+CD74-,EC1), epithelial cells type 2 (PDPL-CD74+, EC2), and transition epithelial cells (PDPL+CD74+, TEC). The EC1 decreased, but EC2 was increased in BPA-exposed mice. The population of TEC was comparable to that in the control group at the low dose (LD) but decreased in the high dose (HD) BPA-treated groups. A significant increase in PDPL, CD74 receptor expression and apoptosis and necrosis in BPA-treated ovarian cells was seen. The RT-qPCR results suggest that the relative expression levels of pro-apoptotic (Bax and Casp3) and anti-apoptotic Cytc were markedly decreased, but Bcl2 expression was increased. The anti-inflammatory (IFN-γ, TNF-α, TGF-β, IL-6) gene expression was reduced, but NF-kB expression was increased. Hypoxia regulator (Hif-1α and Nrf2) and tumour suppressor genes (p53 and p21) were also decreased. Thus, BPA exposure changes EC diversity, induces mortality and alters antioxidant, apoptotic and inflammatory gene expression in ovary.

To evaluate the amount of bisphenol-A (BPA) released from different orthodontic appliances into saliva and plasma and to compare BPA levels between orthodontic appliance groups.

This non-randomized clinical trial included 78 patients, and they were divided into four groups: fixed appliance, temporary anchorage devices (TADs), removable appliance, and functional appliance groups. Saliva and plasma samples were collected before treatment/appliance wear (T0) and one day (T1), one week (T2), and one month (T3) after treatment/appliance wear. Saliva and plasma BPA levels were analysed using Ultra-performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS). Data was analysed using analysis of variance (ANOVA) and Tukey HSD multiple comparison tests with Bonferroni correction. Correlations between saliva and plasma BPA levels at different time points were evaluated using Pearson correlation analysis.

BPA levels ranged from 0.07-7.28 ng/ml in saliva samples and from 0.17-12.51 ng/ml in plasma samples in all groups. Within-group comparisons showed no significant changes over time (p > 0.0125) in each group. Between-group comparisons showed significantly higher saliva BPA levels in the fixed appliance group compared to the other groups (p < 0.017), with no significant differences in plasma BPA levels between groups (p < 0.0175). Positive correlations were observed between saliva BPA measurements, whereas positive correlation was observed only between T0 and T3 plasma PBA levels.

This research obviously demonstrated that the orthodontic appliances we investigated release BPA into the saliva. However, the BPA levels detected in both saliva and plasma are consistently within the acceptable safety limits. However, precautions should be taken to minimize BPA release during orthodontic treatment.

The Constitutive Androstane Receptor (CAR) (NR1I3), a pivotal member of the xenosensor family, plays a key role in the hepatic detoxification of xenobiotic and endobiotic chemicals through the induction of the expression of drug-metabolizing enzymes and transporters. CAR's involvement extends beyond detoxification, influencing gluconeogenesis, lipogenesis, bile acid regulation, and cellular processes such as proliferation, tissue regeneration, and carcinogenesis. This review explores CAR regulation by various factors, highlighting its role in mediating metabolic changes induced by environmental contaminants.

A literature search was conducted to identify all articles on the PubMed website in which the CAR-contaminant and CAR-hepatic steatosis relationship is analyzed in both in vitro and in vivo models.

Numerous contaminants, such as perfluorooctanoic acid (PFOA), Zearalenone mycotoxin, PCB, triazole fungicide propiconazole can activate hepatic nuclear receptors contributing to the development of steatosis through increased de novo lipogenesis, decreased fatty acid oxidation, increased hepatic lipid uptake, and decreased gluconeogenesis. Indirect CAR activation pathways, particularly involving PFOA, are discussed in the context of PPARα-independent mechanisms leading to hepatotoxicity, including hepatocellular hypertrophy and necrosis, and their implications in nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD). The prevalence of NAFLD, a significant component of metabolic syndrome, underscores the importance of understanding CAR's role in its pathogenesis.

Experimental and epidemiological data suggest that endocrine disruptors, especially pesticides, play a significant role in NAFLD's development and progression via CAR-regulated pathways. This review advocates for the inclusion of modern toxicological risk assessment tools, such as New Approach Methodologies (NAMs), Adverse Outcome Pathways (AOPs), and Integrated Approaches to Testing and Assessment (IATA), to elucidate CAR-mediated effects and enhance regulatory frameworks.

Mammary glands development is influenced by endocrine signaling, which remodels epithelial and stromal compartments. Reactive stroma phenotype is observed when stromal disturbances occur, leading to changes in extracellular matrix composition and occurrence of reactive cell types. One of the triggers of these alterations is endocrine-disrupting chemical exposure, such as bisphenol A (BPA). Studies suggest that BPA acts on receptor binding sites of several hormones interfering the endocrine response. The aim of this study was to investigate the reactive stroma features on mammary glands of aged female gerbils (Meriones unguiculatus) exposed to BPA during windows of susceptibility. Thus, the analysis of cellular profile and growth factor expressions was provided. Fibroblastic population changed in BPA-exposed mammary glands, with a remarkable increase of myofibroblasts (vimentin+/α-SMA+) and active fibroblasts (FAP+). Normal fibroblasts (vimentin+/α-SMA-) were decreased mainly associated with the increase of FGF-10, an inductor of fibroblastic polarization. CD34+ stromal cells were also identified and detected among epithelial cells after BPA-induction disruption. Angiogenesis was supported by VEGF increasing in the gland tissue, which promoted an increase in blood vessel density. Thus, our results demonstrated that reactive stroma was raised in the mammary gland after BPA exposure. This profile was supported by changes in the fibroblastic population due to an induction to synthetic phenotypes and the expression of FGF-10, as well as the angiogenic activity that could corroborate with the malignancy and aggressiveness induced by BPA exposure.

The robust redox cycle of the catalytic center is essential for enhancing sustainable water purification in Fenton-like catalysis. However, the unequal of electron donation and acceptance, especially slow reductive half-reactions, often limit the process. Herein, we developed a photocatalytic heterojunction by integrating cuprous oxide (Cu2O) with hexagonal boron nitride (h-BN). The h-BN component acts as an electron sink, promoting electron-hole pair separation and efficient Cu+ regeneration. This design enhances peroxymonosulfate (PMS) activation for bisphenol A (BPA) degradation, achieving rate constants 3.79 and 12.22 times higher than Cu2O/PMS/Light and Cu2O/PMS systems, respectively. Moreover, the formation of the heterojunction optimizes the electronic structure of Cu2O by upshifting the d-band center. This results in stronger PMS adsorption compared to pristine Cu2O. Enhanced surface binding weakens the O-O bond in PMS, enabling a shift from a nonradical to a mixed radical-nonradical degradation pathway for BPA. This strategy offers an effective approach of heterostructures to modulating both the kinetics and pathways of Fenton-like catalysis for environmental remediation.

Methods for evaluation of immobilized-small molecule-binding aptamers are rare. In this study, taking the evaluation of 17β-Estradiol (E2) aptamers as an example, we first summarized the reported affinity and specificity results of 16 E2 aptamers, highlighting the issues of insufficient and inconsistent results and the lacking of evaluation of immobilized aptamers. We further exemplified the limited application scope of current affinity techniques by testing the two most widely-applied E2 aptamers, Kim76 and Alsa35, using the three label-free fluorescence assays and two nuclease protection assays. Subsequently, we evaluated the affinity of immobilized-E2 aptamers, Alsa35 and E09, using fiber optic evanescent wave aptasensor (FOEW) based on the competitive binding of target and fluorophore-labeled complementary strand with the fiber surface immobilized-aptamer. The results revealed that Alsa35 had the better affinity and specificity than E09. Using Alsa35-based FOEW, the enzyme-free detection of E2 spiked in river water and human serum was respectively realized with the unprecedented limits of detection (LOD, S/N = 3) of 4.75 (undiluted river water) and 206 pM (undiluted serum). FOEW is a valuable addition to analytical approaches for evaluation of immobilized-aptamers and a general platform for ultrasensitive target detection.

Bisphenol A (BPA) is widely used in the manufacturing of plastics. BPA can pass the placental barrier and influence fetal development. Due to its estrogenic and anti-androgenic properties, BPA may contribute sex-specific differences in developmental effects. We examined associations between maternal urinary concentrations of BPA and birth size.

In this cohort study of 832 mother-child pairs from the Odense Child Cohort, pregnant women provided spot urine samples at gestational week 28, which were analyzed for BPA by isotope diluted LC-MS/MS. Osmolality adjusted urinary BPA concentrations were categorized into quartiles. Mother-child characteristics were obtained from hospital records and questionnaires. Linear regression analyses examining the association between BPA concentrations and offspring birth size (weight, length, head, and abdominal circumference) were performed for the full cohort and stratified by offspring sex.

BPA was detected above the limit of detection in 85% of the urine samples with a median concentration of 1.33 ng/ml. In the full cohort, birth weight decreased significantly across increasing quartiles of maternal urinary BPA concentration, with the exception of the third quartile, which showed no significant association. In sex-stratified analyses, statistically significant decreases in birth weight were observed among male offspring in the highest quartile of maternal urinary BPA concentrations (β: -115 g, 95% CI: - 225, -4, p = 0.04) compared to male offspring of the lowest quartile and a possible dose-response association was suggested (p-trend = 0.06). No statistically significant associations were observed for birth weight amongst female offspring.

Our findings suggest a negative association between maternal urinary BPA exposure and birth weight, driven by a lower birth weight in male offspring. Further research is required to explore the underlying mechanisms of BPA's possible sex-specific associations.

Systemic lupus erythematosus (SLE) is an autoimmune disease with unclear etiology. T cell exhaustion (TEX) suppresses the immune response and can be a potential therapeutic strategy for autoimmune diseases. Therefore, this study primarily investigated the mechanism by which TEX influences SLE, offering a novel target for its treatment.

GSE72326 and GSE81622 were utilized in this study. TEX related genes (TEX-RGs) were obtained from the published literature. Differentially expressed genes (DEGs) were obtained through differential expression analysis. Subsequently, candidate genes were selected by overlapping DEGs and TEX-RGs. These candidate genes underwent protein-protein interactions (PPIs) analysis for further screening. Machine learning was applied to identify candidate key genes from the PPI-identified genes. The candidate key genes exhibiting an area under the receiver operating characteristic (ROC) curve (AUC) greater than 0.7, along with consistent expression trends and significant differences in GSE72326 and GSE81622 were defined as biomarkers. Additionally, enrichment analysis, immune infiltration analysis, chemical compounds prediction and molecular docking were carried out. Importantly, the biomarkers were validated for expression by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

The biomarkers MX1, LY6E, IFI44 and OASL were screened by overlapping 327 DEGs and 1,408 TEX-RGs. Gene set enrichment analysis (GSEA) showed that there was a significant positive correlation between the expression of these biomarkers and immune-related pathways, such as the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway and RIG-I-like receptor signaling pathway significant positive correlation. The immune infiltration of 8 types of immune cells differed significantly in SLE. Naive B cells, resting memory CD4 T cells and resting NK cells were significantly down-regulated in the SLE group. 4 biomarkers showed the highest correlation with resting memory CD4 T cells. Bisphenol A targeted OASL and LY6E, whereas acetaminophen targeted IFI44 and MX1.The binding activity between the biomarkers and the chemical compounds targeting them was very strong. Finally, RT-qPCR expression of MX1, LY6E, IFI44 and OASL was consistent with the results of the dataset.

MX1, LY6E, IFI44 and OASL were identified as biomarkers related to TEX in SLE. These biomarkers could be detected in the blood for early diagnosis of the disease or to monitor the efficacy of the disease treatment, thus providing a new target for the management of SLE.

Bisphenol A (BPA) is a plasticizer known to have various adverse effects on humans and animals. Exposure of farm animals to BPA negatively impacts their health and poses a threat to humans who consume products of animal origin. Despite the importance of studying the exposure of farm animals to BPA, the knowledge in this area is quite limited. To date, the assessment of BPA levels in dairy cows using analysis of hair samples has not been performed. The study utilized liquid chromatography-mass spectrometry to analyze hair samples collected from 48 dairy cows in the following regions of Kyrgyzstan: Sokuluk, Alamedin and Ysyk Ata. BPA levels above the limit of detection (LOD = 4.8 pg/mg) were noted in 18.8% of analyzed samples. BPA levels in individual samples ranged from below LOD to 89.1 pg/mg with a median value of 9.3 ± 19.7 pg/mg. The study indicates that dairy cows are exposed to BPA, and hair samples can be used for BPA biomonitoring in farm animals. The present study is the first investigation of BPA levels in cows' hair, which is one of the best matrices to study long-term exposure of living organisms to environmental pollutants. Additionally, this study is the first to analyze BPA in biological samples from Kyrgyzstan.

Non-obstructive azoospermia (NOA) constitutes one of the most severe forms of male infertility. Recent advancements in single-cell sequencing have significantly contributed to understanding the molecular landscape of NOA in human testicular tissues, elucidating the factors that underpin spermatogenic dysfunction. This technology has improved our understanding of the condition at a cellular level. Concurrently, bioinformatics developments have facilitated the re-analysis of publicly available single-cell datasets, offering novel insights into the disorder. Nevertheless, a comprehensive review integrating primary and re-analysis studies of single-cell sequencing in NOA is lacking. This review systematically evaluates 10 primary studies reporting original single-cell sequencing data of human NOA testicular samples and 22 secondary studies that re-analyzed these published data. We explore single-cell sequencing applications in germ cells, Sertoli cells, and Leydig cells, offering a comprehensive overview of molecular insights into spermatogenic dysfunction. Our review highlights novel findings in secondary studies, including the roles of transcriptional regulators, RNA transcription, endocrine disruptors, and microtubular cytoskeleton, thereby bridging primary studies and re-analysis studies. Additionally, we discussed future research directions and the challenges of translating single-cell research findings into clinical applications. In summary, single-cell sequencing offers a high-resolution, single-cell perspective of NOA testicular tissue, paving the way for innovative therapeutic strategies in male infertility.

This comprehensive review of dental resin adhesives explores their historical development, key components, recent innovations, and potential future directions, highlighting a dynamic and continually advancing field. From Buonocore's breakthrough acid-etching technique and Bowen's pioneering dental resin invention, successive generations of clinicians and scientists have pushed forward the technological and materials development for secure bonding, while preserving dental tissues. The review discusses the substantial advances in improving adhesive reliability, enabling more conservative treatment approaches. It also delves into enhancing fundamental adhesive components and their synergistic combinations. Recent innovations, including biostable and functional resins, nanotechnology, and bioactive components, address persistent challenges such as durability, antimicrobial efficacy, and therapeutic functionality. Emerging technologies, such as digital dentistry, artificial intelligence, and bioinspired adhesives, portend an exciting and promising future for dental adhesives. This review underscores the critical role of ongoing research in developing biocompatible, multifunctional, and durable adhesives. It aims to support dental professionals and researchers by providing a comprehensive understanding of the dynamic progression of dental adhesives, inspiring continued innovation and excellence in restorative dentistry.

Perinatal exposures to the environmental estrogen bisphenol A (BPA) are associated with increased asthma prevalence. We tested the hypothesis that perinatal BPA exposure transgenerationally enhances allergic asthma development through the bromodomain-containing protein 4 (BRD4) - zinc finger HHC-1 (ZDHHC1) - stimulators of IFN genes (STING) axis. Female BALB/c mice (F0) were exposed to 10 μg/mL BPA in their drinking water during pregnancy until F1 pups were weaned. Pups were sensitized with low doses of ovalbumin (OVA) on postnatal day 4 (PND 4) and 1% OVA inhaler on PND 18-20. Asthma phenotype was assessed on PND 22. Non-sensitized female pups were bred with non-exposed male mice at 8 weeks of age. Subsequent pups were sensitized, and asthma phenotypes were examined for four generations (F1-F4). Maternal BPA exposure significantly enhanced airway hyperresponsiveness, eosinophilic inflammation, and allergen-specific IgE production in F1-3 pups. Further, treatment of F0 dams with STING inhibitor C-176 yielded pups with decreased response to sensitization. Thus, prenatal exposure to environmental estrogens such as BPA may promote development of experimental asthma through the BRD4-ZDHHC1-STING axis, causing immune alterations with multigenerational effects.

This study investigated the neuroprotective effect of ferulic acid (FA) against bisphenol A (BPA) induced Alzheimer's disease-like pathology in male rats.

Rats were allocated into four groups, control, BPA, BPA + FA, and FA, respectively, for 40 days. Spatial working memory and recognition memory were evaluated. Moreover, the brain levels of oxidative stress biomarkers, proinflammatory cytokines, extracellular signal-regulated kinase (ERK), and phosphorylated serine/threonine protein kinase (p-Akt) were measured. We also determined the brain neuropathological protein levels, including Beta-Amyloid 1-42, total Tau (tTau), and phosphorylated Tau (pTau) proteins. Furthermore, brain levels of Acetylcholinesterase (AChE) and Beta-secretase (BACE) were assessed. Brain histological investigation and immunohistochemistry determination of glial fibrillar acidic protein (GFAP) were also performed. Moreover, docking simulation was adapted to understand the inhibitory role of FA on AChE, BACE-1, and ERK1/2.

Interestingly, the BPA + FA treated group showed a reversal in the cognitive impairments induced by BPA, which was associated with improved brain redox status. They also exhibited a significant decrease in brain inflammatory cytokines, ERK, and p-Akt levels. Moreover, they revealed a decline in beta-amyloid 1-42 and a significant improvement in tTau expression and pTau protein levels in the brain tissue. Further, the brain levels of AChE and BACE were substantially reduced in BPA + FA rats. The neuroprotective effect of FA was confirmed by restoring the normal architecture of brain tissue, which was associated with decreasing GFAP.

FA could be a potent neuroprotectant agent against AD with a possible prospect for its therapeutic capabilities and nutritional supplement value due to its antioxidant and antiapoptotic properties.

Bisphenols are frequently found in a range of plastic products and have been associated with the development of diseases such as diabetes mellitus type 2 and obesity. These compounds are known as endocrine disruptors and have led to restrictions on their use due to their presence in the environment and their association with non-communicable chronic diseases. The gastrointestinal tract, being the primary site of food and water absorption, is particularly vulnerable to the effects of bisphenols. For this reason, a review of studies showing associations between bisphenols exposure and adverse effects in the gut microbiota, morphology tissue, gut permeability, and on the enteric nervous system was carried out. We have included perinatal studies and in different adult experimental models. The effects of bisphenol exposure on the gut microbiota are complex and varied. Bisphenol exposure generally leads to a decrease in microbial diversity and may impact the integrity of the intestinal barrier, resulting in elevated levels of inflammation, changes in morphological and metabolic characteristics of the gut, modifications in tight junction expression, and changes in goblet cell expression. In addition, bisphenol exposure in the perinatal phase can lead to important intestinal changes, including increased colonic inflammation and decreased colonic paracellular permeability.

Bisphenol A (BPA) is a ubiquitous industrial compound found in an enormous variety of consumer goods such as plastics, epoxy resins, and thermal paper. Despite its widespread usage, the effects of BPA on the risk and development of metabolic syndrome are not fully understood. Prenatal exposure to BPA has been shown to disrupt the development of offspring's metabolically active tissues and increase their susceptibility to the adverse consequences of a trans-fat diet (TFD).

In this experiment, pregnant rats (n = 18) were randomly separated into three groups. These groups were treated from pregnancy day (PD) 2 to PD 21. Subsequently, the male offspring of these rats were provided either a normal-diet (ND) or a TFD from 3rd postnatal week (PNW) to 14th PNW. Then, protein expression of PPAR-γ and global DNA methylation were assessed in the adult rat offspring that were exposed to in utero BPA and subjected to postnatal TFD intake.

The study findings have shown that there was no association between prenatal exposure to BPA and/or TFD consumption and PPAR-γ protein expression within all the study groups in the liver tissue. On the other hand, changes at the molecular level, as reflected by the global DNA hypermethylation induced by prenatal BPA and postnatal TFD intake in adult male SD rat offspring (PNW 14).

This study underscores the potential impact of prenatal BPA exposure and postnatal TFD intake on epigenetic regulation, as evidenced by global DNA hypermethylation, despite no observable changes in PPAR-γ protein expression. These findings suggest that early-life environmental exposures may predispose individuals to metabolic disruptions, including diabetes and obesity, in adulthood or future generations.

The extensive use of bisphenols in the plastics industry globally is a major growing concern for human health. Bisphenol compounds are easily leached out from plastic containers to food, beverages, and drinking water and contaminate the natural environment. Daily exposure of bisphenol compounds increases their load and impairs various organs, including the reproductive system. Bisphenol compounds directly or indirectly affect ovarian functions, such as folliculogenesis, steroidogenesis, oogenesis, and thereby oocyte quality. Bisphenol A (BPA) and its structural analogues act as endocrine disruptors and induce generation of reactive oxygen species (ROS) within the ovary. Excess levels of ROS induce death pathways in follicular steroidogenic cells and affect ovarian steroidogenesis. The reduced level of estradiol-17β impairs follicular growth and development that reduces the number and quality of oocytes. In addition, excess levels of ROS in follicular fluid trigger meiotic instability, which further deteriorates oocyte quality. The high level of ROS generates oxidative stress that triggers various death pathways in germ cells as well as in oocytes, induces follicular atresia, and depletes ovarian reserve. Although growing evidence indicates the destructive effects of bisphenol compounds at the level of ovary, potential effects and underlying mechanisms that deteriorate oocyte quality remain poorly understood. Therefore, this review summarizes the mechanisms by which bisphenols cause damage to the ovary, impair oocyte quality, and affect women's fertility.

Bisphenol A (BPA) is an organic synthetic chemical used worldwide. Billions of pounds of BPA are produced annually through industrial processes to be used in commercial products, making human exposure to BPA ubiquitous. Concerns have been raised due to the potential adverse health effects of BPA, specifically in vulnerable populations, such as pregnant persons and children. BPA is an endocrine-disrupting chemical, and through this function has been linked to reproductive toxicity. We review BPA's historical and current use, health and safety concerns and regulations, sources of exposure, and evidence for male and female reproductive toxicity. Evidence from epidemiological and animal studies idenfity that low- and high-exposure levels of BPA (prenatal, postnatal and adulthood exposure) can adversely affect male and female fertility and reproductive organs. While the cause of BPA-induced reproductive toxicity is not fully understood, we discuss BPA's estrogenic and androgenic activity, and its ability to disrupt the hypothalamic-pituitary-gonadal axis as a potential associated mechanism. There are significant differences in tolerable daily intakes of BPA set by global agencies, making interpretation of previous and emerging research findings challenging and inconsistent. Although BPA is deemed toxic by some government agencies, most do not currently consider it a health risk due to low populational exposure levels. However, we highlight evidence that even at acute, low exposure, BPA can adversely affect reproductive function. We recommend continuing research into the adverse effects of BPA on human health and revisiting the regulatory measures of BPA to limit exposure and promote public awareness of its potential to cause reproductive toxicity.

Prenatal exposure to bisphenol analogs (BPs) may pose hazards to offspring's health; however, their underlying mechanisms remain to be elucidated. DNA methylation, a major epigenetic mechanism, may be involved in early programming following environmental disturbances. In this prospective study, we investigated associations between prenatal BPs exposure and the placental DNA methylation levels of 14 candidate genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway among 205 mother-infant pairs and explored the potential mediating role of the DNA methylation in the association of prenatal BPs exposure with anthropometric measurements of infants aged 1 year. We observed a general pattern that prenatal BPs exposure was associated with the DNA hypomethylation of candidate genes, with associations consistently and notably observed for PPAR α (PPARA), retinoid X receptor α (RXRA), acetyl-CoA acyltransferase 1, and acyl-CoA dehydrogenase medium chain (ACADM) in linear regression and Bayesian kernel machine regression. Both models identified bisphenol F (BPF) as the predominant compound. We found inverse associations between the placental DNA methylation levels of most candidate genes, such as PPARA, RXRA, ACADM, and nuclear receptor subfamily 1 group H member 3 (NR1H3), and the length-for-age z-score, arm circumference-for-age z-score, subscapular skinfold-for-age z-score, and abdominal skinfold thickness of the infants. The DNA methylation levels of RXRA and NR1H3 could mediate the associations between prenatal BPF exposure and increased infant anthropometric measurements, with mediating portions ranging from 23.02% to 30.53%. Our findings shed light on the potential mechanisms underlying the effects of prenatal BPs exposure on infant growth and call for urgent actions for risk assessment and regulation of BPF. Future cohort studies with larger sample sizes are warranted to confirm our findings.

Bisphenol S (BPS) is the main substitute for bisphenol A (BPA). However, the neurodevelopmental toxicity of BPS and the underlying mechanisms remain unraveled. In present study, the neuro-differentiating human embryonic stem cells, hESC, was exposed to BPS (0-375 µM) at different stages (the precursor stage, the precursor to maturation stage, and the whole differentiation stage) to assess the potential neurodevelopmental toxicity and its mechanisms. The results revealed that BPS exposure interrupted axonogenesis, manifesting a trend of initial stimulating followed by inhibition, and peaked at the intermediate dose (3.75 μM) significantly, then reached the nadir at the high dose (375 μM) significantly in the precursor to maturation stage and the whole differentiation stage. Transcriptomics analysis showed that the main interrupted pathway enriched in axonogenesis, myelination, and neurotransmitter secretion by the GO function analysis and immune-related pathway by the KEGG analysis, besides, conserved axon guidance (Slit-Robo, Netrin-DCC, Semaphorin-Plexin) and WNT signaling pathway was also enriched in KEGG pathway analysis, which previously proved to regulate axonogenesis by directly acting on growth cones and inhibit axon growth by neuroinflammatory responses. And we found that a higher neuroinflammatory response may be induced through whole-differentiation-stage exposure than the response of exposure through the precursor to maturation stage. Overall, our findings indicated the non-monotonic neurodevelopmental toxicity of BPS exposure, and the inhibition of axonogenesis was possibly mediated by conserved axon guidance and WNT signaling pathway, while neuro-immune related pathway should be further investigated.