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Bisphenol A (BPA) is one of the most prevalent endocrine disrupting chemicals (EDCs) and there is widespread concern about the adverse effects of EDCs on human health. However, the exact mechanism of these toxicities has still not been fully deciphered. Additionally, studies have reported the toxicological effects at far low doses to the generally considered no-observed-adverse-effect level (NOAEL) dose. The present study investigates the effects of a sub-acute (28 days) exposure to BPA (10, 50 and 100 mg/kg/day) in adult male mice on various hormones levels, sperm motility, sperm count, functional integrity of sperm plasma membrane, testicular histological changes, oxidative stress markers and DNA damage. The key proteome signatures were quantified by LC-MS/MS analysis using Orbitrap Fusion Lumos Tribrid Mass Spectrometer equipped with nano-LC Easy-nLC 1200. Data suggest that the BPA exposure in all doses (below/above NOAEL dose) have greatly impacted the hormone levels, sperm parameters (sperm count, motility and membrane integrity) and testicular histology. Mass spectrometry-based proteomics data suggested for 1352 differentially expressed proteins (DEPs; 368 upregulated, 984 downregulated) affecting biological process, cellular component, and molecular functions. Specifically searched male reproductive function related proteins suggested a complex network where 46 potential proteins regulating spermatogenesis, sperm structure, activity and membrane integrity while tackling oxidative stress responses were downregulated. These potential biomarkers could shed some more light on our current understanding of the reproductive toxicological effects of BPA and may lead to exploration of novel interventions strategies against these targets for male infertility., (© 2024 Wiley Periodicals LLC.)

Bisphenol-A (BPA) is an emerging hazardous contaminant, which is ubiquitous in the environment and can cause endocrine disruptor and cancer risks. Therefore, biodegradation of BPA is an essential issue to mitigate the associated human health. In this work, a bacterial strain enables of degrading BPA, named BPA-LRH8 (identified as Xenophilus sp.), was newly isolated from activated sludge and embedded onto walnut shell biochar (WSBC) to form a bio-composite (BCM) for biodegradation of BPA in water. The Langmuir maximum adsorption capacity of BPA by WSBC was 21.7 mg g -1 . The free bacteria of BPA-LRH8 showed high BPA degradation rate (∼100 %) at pH 5-11, while it was lower (＜20 %) at pH 3. The BCM eliminated all BPA (∼100 %) at pH 3-11 and 25-45 °C when the BPA level was ≤ 25 mg L -1 . The spectrometry investigations suggested two possible degradation routes of BPA by Xenophilus sp. In one route, BPA (C 15 H 16 O 3 ) was oxidized to C 15 H 16 O 3 , and then broken into C 9 H 12 O 3 through chain scission. In another route, BPA was likely hydroxylated, oxidized, and cleaved into C 9 H 10 O 4 P 4 , which was further metabolized into CO 2 and H 2 O in the TCA cycle. This study concluded that the novel isolated bacteria (BPA-LRH8) embedded onto WSBC is a promising and new method for the effective removal of BPA and similar hazardous substances from contaminated water under high concentrations and wide range of pH and temperature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, visible light-activated photocatalyst oxygen-doped C 3 N 4 @Bi 12 O 17 Cl 2 (OCN@BOC) and Fe(VI) coupling system was proposed for the efficient degradation of bisphenol A (BPA). The comprehensive characterization of the OCN@BOC photocatalyst revealed its excellent photogenerated carrier separation rate in heterogeneous structures. The OCN@BOC/Fe(VI)/Vis system exhibited a remarkable BPA removal efficiency of over 84% within 5 min. Comparatively, only 37% and 59% of BPA were degraded by single OCN@BOC and Fe(VI) in 5 min, respectively. Reactive species scavenging experiments, phenyl sulfoxide transformation experiments, and electron paramagnetic resonance experiments confirmed the involvement of superoxide radicals (⋅O 2 - ), singlet oxygen ( 1 O 2 ), as well as iron(V)/iron(IV) (Fe(V)/Fe(IV)) species in the degradation process of BPA. Furthermore, density functional theoretical calculations and identification of intermediates provided insights into the potential degradation mechanism of BPA during these reactions. Additionally, simulation evaluations using an ecological structure activity relationship model demonstrated that the toxicity of BPA to the ecological environment was mitigated during its degradation process. This study presented a novel strategy for removing BPA utilizing visible light photocatalysts, highlighting promising applications for practical water environment remediation with the OCN@BOC/Fe(VI)/Vis system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Social behavior is sexually dimorphic, which is regulated by gonadal hormones in the brain. Our recent study found that exposure to low doses of bisphenol-A (BPA) during adolescence, permanently alters social behavior in adult male mice, but the underlying mechanisms remain unclear. Using adolescent gonadectomy (GDX) male mice with testosterone propionate (TP, 0.5 mg/kg) supplement (TP-GDX), this study showed that BPA antagonized promoting effects of TP on social interaction, sexual behavior, and aggression in GDX mice. BPA eliminated the reversal effects of TP on GDX-induced decrease in the number of immunoreactive to arginine vasopressin (AVP-ir) neurons in the medial amygdala (MeA) and the levels of AVP receptor 1a (V1aR) in the MeA and the nucleus accumbens (NAc). In addition, BPA removed down-regulation in the levels of dopamine (DA) transporter (DAT) and DA receptor 1 (DR1) in the NAc of TP-GDX mice. BPA exposure reduced testosterone (T) levels in the brain and serum and the expression of androgen receptor (AR) protein in the amygdala and striatum of sham-operated and TP-GDX males. These results suggest that adolescent exposure to BPA inhibits regulation of androgen in AVP and DA systems of the brain regions associated with social behavior, and thus alters social behaviors of adult male mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Bisphenol-A (BPA), a known endocrine-disrupting chemical (EDC) in plastics and resins, has been found to induce heritable health effects in fish and mammals, affecting directly exposed individuals and indirectly their progenies in subsequent generations. It is not clearly understood if subsequent generations of the BPA-exposed ancestors have increased sensitivity to the second hit by the chemicals of emerging concern. To understand this, the present study examined the effects of developmental exposure to perfluorooctanesulfonic acid (PFOS), which has been a global contaminant recently, in embryos whose ancestors were exposed to BPA. Two lineages of medaka (Oryzias latipes) were established: 1) the BPA lineage in which the F0 generation was exposed to 10 μg/L BPA during early development and 2) the control lineage with no BPA exposure in the F0 generation. These lineages were raised up to the F4 generation without further exposure. The embryos of the F4 generation were exposed to PFOS at 0, 0.002, 0.02, 0.2, 2, and 20 mg/L concentrations. Early developmental defects resulting in mortality, delayed hatching, teratogenic phenotypes, and altered gene expression were examined in both lineages. The expression level of genes encoding DNA methyltransferases and genes responsible for oxidative stress defense were determined. Following environmentally relevant PFOS exposure, organisms with a history of BPA exposure displayed significant changes in all categories of developmental defects mentioned above, including increased expression of genes related to oxidative stress, compared to individuals without BPA exposure. The present study provides initial evidence that a history of ancestral BPA exposure can alter sensitivity to developmental disorders following the second hit by PFOS exposure. The variable of ancestral BPA exposure could be considered in mechanistic, medical, and regulatory toxicology, and can also be applied to holistic environmental equity research., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables ( β  = 0.003, p  < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 μg/g creatinine vs. 1.71 μg/g creatinine [ p  < 0.05]; cord blood BPA, 1.96 μg/L vs. -0.86 μg/L [ p  < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR., Competing Interests: MY and HWK were employed by the company Goodbeing Center Co. Ltd., Republic of Korea. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hong, Kang, Kim, Won, Kim, Wie, Shin, Choi, Jo, Kim, Yang, Kang, Lee, Park, Park and Ko.)

Background: Ferroptosis is a newly recognized cell death pathway having distinct characteristics compared to traditional cell death pathways such as apoptosis, necroptosis, or autophagy. However, the potential involvement of ferroptosis in bisphenol A (BPA)-induced neurotoxicity has not been well explored so far. In present study, we analyzed the relationship between ferroptosis and BPA-induced neurotoxicity., Methods: In this study, a human neuroblastoma cell line, SH-SY5Y, was treated with BPA, ferrostatin-1 (FS-1, ferroptosis inhibitor) and RSL-3 (ferroptosis inducer). The cell viability was measured using MTT assay. Additionally, the levels of lipid peroxidation, total iron content, reactive oxygen species (ROS) generation, and nitrite content were measured to evaluate the key markers of ferroptosis. To further confirm the involvement of ferroptosis in BPA-induced neurotoxicity, other ferroptosis markers such as glutathione peroxidase (GPx) activity, total glutathione contents and antioxidant parameters were also evaluated., Results: The cell viability of SH-SY5Y cells was down-regulated by BPA treatment in a concentration-dependent manner, the cell viability at 0.1 µM concentration was 97.63% whereas at highest BPA concentration i.e. 10 µM, the cell viability was 86.05% (p < 0.0001). Also the antioxidant parameters including catalase and superoxide dismutase activity of neuronal cells were down-regulated upon BPA exposure. However, the levels of lipid peroxidation, total iron, reactive oxygen species, and nitrite contents were increased in a concentration-dependent manner which could be rescued by FS-1 and exacerbated by RSL-3. The total iron in SH-SY5Y cells at 0.1 µM concentration was found to be 1.2 fold (p < 0.05) of control and at highest BPA concentration total iron was about 1.41 fold (p < 0.001) of control., Conclusions: The present study indicated that, ferroptosis plays an important role in the progression of BPA-induced neurotoxicity, and ferroptosis may become a novel target in the treatment of various neurological disorders., Competing Interests: Declaration of Competing Interest Authors do not have any type of conflict of interest to disclose. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ankita Sharma reports administrative support and equipment, drugs, or supplies were provided by National Institute of Pharmaceutical Education and Research Raebareli. Nidhi Srivastava reports administrative support and equipment, drugs, or supplies were provided by National Institute of Pharmaceutical Education and Research Raebareli. Nita Jangid reports administrative support and equipment, drugs, or supplies were provided by National Institute of Pharmaceutical Education and Research Raebareli. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Three-dimensional (3D) hierarchical microspheres of Bi 12 O 17 Cl 2 (BOC) were prepared via a facile solvothermal method using a binary solvent for the photocatalytic degradation of Rhodamine-B (RhB) and Bisphenol-A (BPA). Co 3 O 4 nanoparticles (NPs)-decorated BOC (Co 3 O 4 /BOC) heterostructures were synthesized to further enhance their photocatalytic performance. The microstructural, morphological, and compositional characterization showed that the BOC microspheres are composed of thin (~20 nm thick) nanosheets with a 3D hierarchical morphology and a high surface area. Compared to the pure BOC photocatalyst, the 20-Co 3 O 4 /BOC heterostructure showed enhanced degradation efficiency of RhB (97.4%) and BPA (88.4%). The radical trapping experiments confirmed that superoxide ( • O 2 - ) radicals played a primary role in the photocatalytic degradation of RhB and BPA. The enhanced photocatalytic performances of the hierarchical Co 3 O 4 /BOC heterostructure are attributable to the synergetic effects of the highly specific surface area, the extension of light absorption to the more visible light region, and the suppression of photoexcited electron-hole recombination. Our developed nanocomposites are beneficial for the construction of other bismuth-based compounds and their heterostructure for use in high-performance photocatalytic applications.

The regulatory network of mitochondrial biogenesis and dynamics is vital for mitochondrial functions and cellular homeostasis. Any impairment in the mitochondrial network leads to neurodegenerative disorders. Our earlier studies suggest that environmental toxicant Bisphenol-A (BPA) exposure reduces neurogenesis by abnormal mitochondrial dynamics and mitochondrial biogenesis through impairment of mitochondrial fission factor dynamin-related protein (DRP1) and mitochondrial import protein GFER, which leads to demyelination, neurodegeneration, and cognitive deficits in the rats. In the present study, we found that chronic BPA exposure reduces PGC-1α levels (master regulator of mitochondrial biogenesis), alters mitochondrial localization of DRP1 and GFER, and reduces the number of PGC-1α/NeuN + and PGC-1α/β-tubulin + neurons in the rat hippocampus, suggesting reduced PGC-1α-mediated neurogenesis. Nicotinamide significantly increased PGC-1α protein levels, PGC-1α/NeuN+ co-labeled cells in BPA-treated rat hippocampus and PGC-1α/β-tubulin+ co-labeled cells in neuron culture derived from hippocampal neural stem cells. Interestingly, PGC-1α upregulation by nicotinamide also resulted in increased GFER levels and restored mitochondrial localization of GFER (increased GFER/TOMM20 co-labeled cells) in vitro and in vivo following BPA treatment. Nicotinamide also reduced DRP1 levels and prevented DRP1 mitochondrial localization in BPA-treated neuronal cultures and hippocampus, suggesting reduced mitochondrial fission. This resulted in reduced cytochrome c levels in neuronal culture and reduced hippocampal neurodegeneration (reduced caspase-3/NeuN + co-labeled neurons) following nicotinamide treatment in BPA-treated group. Consequently, activation of PGC-1α by nicotinamide restored BPA-mediated cognitive deficits in rats. Results suggest that the treatment of nicotinamide has therapeutic potential and rescues BPA-mediated neuronal death and cognitive deficits by upregulating the PGC-1α and GFER-DRP1 link, thus balancing mitochondrial homeostasis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Bisphenol-A (BPA) has estrogenic activity and adversely affects humans and animals' reproductive systems and functions. There has been a disagreement with the safety of BPA exposure at Tolerable daily intake (TDI) (0.05 mg/kg/d) value and non-observed adverse effect level (5 mg/kg/d). The current study investigated the effects of BPA exposure at various doses starting from Tolerable daily intake (0.05 mg/kg/d) to the lowest observed adverse effect level (50 mg/kg/d) on the testis development in male mice offspring. The BPA exposure lasted for 63 days from pregnancy day 0 of the dams to post-natal day (PND) 45 of the offspring., Results: The results showed that BPA exposure significantly increased testis (BPA ≥ 20 mg/kg/d) and serum (BPA ≥ 10 mg/kg/d) BPA contents of PND 45 mice. The spermatogenic cells became loose, and the lumen of seminiferous tubules enlarged when BPA exposure at 0.05 mg/kg/d TDI. BPA exposure at a low dose (0.05 mg/kg/d) significantly reduced the expression of Scp3 proteins and elevated sperm abnormality. The significant decrease in Scp3 suggested that BPA inhibits the transformation of spermatogonia into spermatozoa in the testis. The RNA-seq proved that the spliceosome was significantly inhibited in the testes of mice exposed to BPA. According to the RT-qPCR, BPA exposure significantly reduced the expression of Snrpc (BPA ≥ 20 mg/kg/d) and Hnrnpu (BPA ≥ 0.5 mg/kg/d)., Conclusions: This study indicated that long-term BPA exposure at Tolerable daily intake (0.05 mg/kg/d) is not safe because low-dose long-term exposure to BPA inhibits spermatogonial meiosis in mice testis impairs reproductive function in male offspring., (© 2022. The Author(s).)

Bisphenol-A (BPA) is widely used in production of plastic products. It can reach the ecosystems affecting aquatic organisms most likely fishes. The purpose of this study was to study the toxic effects of BPA on the biochemical variables and oxidative stress in female African catfish, Clarias gariepinus and to estimate the protective role of chitosan nanoparticles (CSNPs) against BPA toxicity. Five groups in triplicates of fish were divided as follows: group I was control, group II was treated with CSNPs (0.66 ml/L), group III was exposed to BPA (1.43 μg/L), group IV was treated with BPA (1.43 μg/L) plus CSNPs (0.33 ml/L), and group V was treated with BPA (1.43 μg/L) plus CSNPs (0.66 ml/L) for 30 days. Blood and liver tissue samples were collected at the end of experiment for the biochemical and oxidative stress biomarkers analyses. Results exhibited that serum Follicle Stimulating Hormone (FSH) and 17-β Estradiol (E2) were significantly decreased in female catfish. While, serum Testosterone (T.) and Luteinizing Hormone (LH) were increased after exposure to BPA. Marked increment in superoxide dismutase (SOD) and malondialdehyde (MDA) levels of hepatic tissue of catfish exposed to BPA. Furthermore, significant reduction in hepatic catalase (CAT), glutathione peroxidase (GSH-px), total antioxidant capacity (TAC), reduced glutathione (GSH), and glutathione S-transferase (GST) levels were decreased significantly in BPA-exposed catfish compared to the control group. However, administration of female C. gariepinus with the low and high doses (0.33 ml/L and 0.66 ml/L) of CNPs restored the biochemical parameters to be close to the normal values of the control group and also, reduced oxidative stress induced by BPA toxicity. This improvement was evident in fish administrated with the high CSNPs dose (0.66 ml/L) compared to catfish exposed to BPA in group (III). Furthermore, the percentage of hepatic DNA damage was detected in group III exposed to BPA alone. However, it was declined after co- administration with both the low and high doses of CSNPs. The study has revealed that treatment with CSNPs has antagonistic functions against the toxicity of BPA in female African catfish., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Human exposure to bisphenol-A (BPA) is largely unavoidable because BPA is an environmental contaminant found in soil, water, food and indoor dust. The safety of authorized BPA amounts in consumer products is under question because new studies have reported adverse effects of BPA at doses far below that previously established by the NOAEL (50 μg/kg per day). To protect public health, the consequences of low-dose BPA exposure in different organs and organismal functions must be further studied to generate relevant data. This study attempted to investigate the effects and potential molecular mechanisms of short-term exposure to 1 μg/L BPA on zebrafish ovarian follicular development. We observed only minor changes at the histopathological level with a small (3 %) increase in follicular atresia. However, a shotgun proteomics approach indicated deep alterations in BPA-exposed ovarian cells, including induction of the oxidative stress response, metabolic shifts and degradome perturbations, which could drive oocytes towards premature maturation. Based on these results, it could be suggested that inadvertent exposure to small concentrations of BPA on a continuous basis causes alteration in biological processes that are essential for healthy reproduction., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Herein, the effects of oven bag use belong to different brands on heterocyclic aromatic amine (HAA) formation and bisphenol-A (BPA) migration in cooked chicken meats (breast and leg) were investigated. Samples were also analyzed in terms of some qualitative properties (fatty acid profile, water, fat, pH, TBARS, cooking loss). Both oven bag use and meat type had an effect on qualitative properties of the samples. Total HAA amount changed between 6.53 and 42.32 ng/g, and HAA content was higher in breast meat. Total BPA content in samples cooked with oven bag ranged between non-quantified to 63.78 ng/g. Oven bag use reduced the total HAA amount at the rate of 12 - 68.82%, while it caused the BPA migration depends on the brand. However, it can be noted that the HAA and BPA levels were not at a level to pose a risk to human health in any of the samples., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Mitochondrial biogenesis relies on different protein import machinery, as mitochondrial proteins are imported from the cytosol. The mitochondrial intermembrane space assembly (MIA) pathway consists of GFER/ALR and CHCHD4/Mia40, responsible for importing proteins and their oxidative folding inside the mitochondria. The MIA pathway plays an essential role in complex IV (COX IV) biogenesis via importing copper chaperone COX17, associated with the respiratory chain. BPA, an environmental toxicant, found in consumable plastics, causes neurotoxicity via impairment in mitochondrial dynamics, neurogenesis, and cognitive functions. We studied the levels of key regulatory proteins of mitochondrial import pathways and mitochondrial biogenesis after BPA exposure in the rat hippocampus. BPA caused a significant reduction in the levels of mitochondrial biogenesis proteins (PGC1α, and TFAM) and mitochondrial import protein (GFER). Immunohistochemical analysis showed reduced co-localization of NeuN with GFER, PGC-1α, and TFAM suggesting impaired mitochondrial biogenesis and protein import. BPA exposure resulted in damaged mitochondria with distorted cristae in neurons and caused a significant reduction in GFER localization inside IMS as depicted by immunogold electron microscopy. The reduced levels of GFER resulted in defective COX17 import. The translocation of cytochrome c into the cytosol and increased cleaved caspase-3 levels triggered apoptosis due to BPA toxicity. Overall, our study implicates GFER as a potential target for impaired mitochondrial protein machinery, biogenesis, and apoptosis against BPA neurotoxicity in the rat hippocampus., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study investigates the effect of environmental risk factors among North Indian children aged between 6 and 16 years associated with body mass index by comparing fasting and non-fasting urine Bisphenol-A, urine creatinine, and serum thyroid levels with other potential confounding factors. A total of 301 children were enrolled, and term fasting and non-fasting were used based on the sample collection, either first morning or random. Children were grouped into obese, non-obese, and underweight categories based on age- and gender-specific Centre for Disease Control (CDC) 2000 growth chart and grouped according to their body mass index. The overall mean ± SD (standard deviation) of age (years) was 10.45±2.39 (boys age 10.38±2.38 and girls age 10.45±2.40). Urinary Bisphenol-A concentration (ng/mL ± SD) was higher among obese (2.40±4.70) than non-obese (1.30±1.67) and underweight (1.84±3.46) category children. Higher levels of fasting urinary Bisphenol-A (≥2 ng/mL) and thyroid-stimulating hormone (TSH) (≥12.7 μg/dL) were associated with obesity than those of non-fasting children. Being non-fasting among girls at quartile 4 (obese, >2.1800 ng/mL; underweight, >2.1325 ng/mL) had higher odds (obese adjusted odds ratio (aOR) 7.72 (95% CI 0.08-1368.52), underweight adjusted odds ratio (aOR) 12.45 (95% CI 1.55-171.24)] than fasting children. We recommend awareness programs and policy guidelines by engaging teachers and parents for the physical assessment of the presence of Bisphenol-A in food packaging materials to reduce the potential exposure to other chemical migrations sources. Graphical abstract.

The objective of this work has been to characterize the estrogenic activity of bisphenol-A (BPA) and the adverse effects on the endocannabinoid system (ECS) in modulating germ cell progression. Male offspring exposed to BPA during the foetal-perinatal period at doses below the no-observed-adverse-effect-level were used to investigate the exposure effects in adulthood. Results showed that BPA accumulates specifically in epididymal fat rather than in abdominal fat and targets testicular expression of 3β-hydroxysteroid dehydrogenase and cytochrome P450 aromatase, thus promoting sustained increase of estrogens and a decrease of testosterone. The exposure to BPA affects the expression levels of some ECS components, namely type-1 (CB1) and type-2 cannabinoid (CB2) receptor and monoacylglycerol-lipase (MAGL). Furthermore, it affects the temporal progression of germ cells reported to be responsive to ECS and promotes epithelial germ cell exfoliation. In particular, it increases the germ cell content (i.e., spermatogonia while reducing spermatocytes and spermatids), accelerates progression of spermatocytes and spermatids, promotes epithelial detachment of round and condensed spermatids and interferes with expression of cell-cell junction genes (i.e., zonula occcludens protein-1, vimentin and β-catenin). Altogether, our study provides evidence that early exposure to BPA produces in adulthood sustained and site-specific BPA accumulation in epididymal fat, becoming a risk factor for the reproductive endocrine pathways associated to ECS.

Exposure to Bisphenol A (BPA) during early development particularly in- utero has been linked to a wide range of pathology. The aim of this study was to examine the relationship of BPA and its naturally occurring metabolite BPA-glucuronide (BPA-g) with sex steroid hormone levels in South African mother-child pairs. Third-trimester serum maternal samples and matching cord blood samples were analyzed for BPA, BPA-g and nine sex steroid hormones using liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixty maternal and child pairs were analyzed. Rank correlation demonstrated a significant positive relationship between cord blood estradiol and cord blood BPA (p = 0.002) and maternal BPA levels (p = 0.02) respectively. Cord blood testosterone from male infants showed a negative Spearman's correlation (r=-0.5, p = 0.02) with maternal BPA-g. There was no statistical difference in total testosterone levels in cord blood from male and female infants. The findings of the current study indicate a significant relationship between some key sex steroid hormones namely testosterone, dihydrotestosterone and estradiol and fetal exposure BPA., (Copyright © 2021. Published by Elsevier Inc.)

Objective: The objectives of this systematic review of the literature are to search for BPA release from biomaterials used in orthodontics and to highlight their possible impact on human health., Materials and Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model, digital and manual searches were conducted in February 2020 in the database of CENTRAL, MEDLINE and EMBASE. Thirteen parameters relating to the release and biological effects of BPA were identified and analysed., Results: Thirty-one non-randomized clinical trials were included. In general, the level of evidence was low, and the risk of bias ranged from moderate to high. Furthermore, although at different concentrations, most of in vitro and in vivo studies found BPA release from orthodontic adhesives. The lack of standardized protocols and the clinical and methodological heterogeneity of the studies prevented a valid interpretation of the actual results. Concerning the possible toxicity of BPA, no conclusive scientific evidence could be drawn, but it seems that orthodontic biomaterials containing BPA have potential adverse biological effects in humans., Discussion and Conclusion: Until we have solid evidence from clinical trials, clinicians should consider that orthodontic adhesives containing BPA have potential short- and long-term adverse biological effects in humans. Careful consideration should therefore be given to bonding, polymerization and debonding protocols in orthodontics., (Copyright © 2020 CEO. Published by Elsevier Masson SAS. All rights reserved.)

Bisphenol-A (BPA) is a ubiquitous precursor of polycarbonate plastics that is found in the blood and serum of >92% of Americans. While BPA has been well documented to act as a weak estrogen receptor (ER) agonist, its effects on cellular stress are unclear. Here, we demonstrate that high-dose BPA causes stress granules (SGs) in human cells. A common estrogen derivative, β-estradiol, does not trigger SGs, indicating the mechanism of SG induction is not via the ER pathway. We also tested other structurally related environmental contaminants including the common BPA substitutes BPS and BPF, the industrial chemical 4-nonylphenol (4-NP) and structurally related compounds 4-EP and 4-VP, as well as the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D). The variable results from these related compounds suggest that structural homology is not a reliable predictor of the capacity of a compound to cause SGs. Also, we demonstrate that BPA acts primarily through the PERK pathway to generate canonical SGs. Finally, we show that chronic exposure to a low physiologically relevant dose of BPA suppresses SG assembly upon subsequent acute stress. Interestingly, this SG inhibition does not affect phosphorylation of eIF2α or translation inhibition, thus uncoupling the physical assembly of SGs from translational control. Our work identifies additional effects of BPA beyond endocrine disruption that may have consequences for human health., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Exposure to endocrine-disrupting chemicals such as Bisphenol-A (BPA) is associated with an increase in obesity prevalence. Diet is the primary cause of human exposure to this contaminant. BPA promotes obesity by inducing adipocyte dysfunction and altering adipogenesis. Contradictory evidence and unanswered questions are reported in the literature concerning the BPA effects on adipogenesis. To clarify this issue, we tested the effects of prolonged low-dose BPA exposure on different phases of adipogenesis in committed 3T3L1 and uncommitted NIH3T3 preadipocytes. Our findings show that BPA effects on the adipogenesis are mediated by epigenetic mechanisms by reducing peroxisome proliferator-activated receptor gamma ( Pparγ ) promoter methylation in preadipocytes. Nevertheless, in BPA-exposed 3T3L1 , Pparγ expression only transiently increases as lipid accumulation at day 4 of differentiation, without altering the adipogenic potential of the precursor cells. In the absence of differentiation mix, BPA does not make the 3T3L1 an in vitro model of spontaneous adipogenesis and the effects on the Pparγ expression are still limited at day 4 of differentiation. Furthermore, BPA exposure does not commit the NIH3T3 to the adipocyte lineage, although Pparγ overexpression is more evident both in preadipocytes and during the adipocyte differentiation. Interestingly, termination of the BPA exposure restores the Pparγ promoter methylation and inflammatory profile of the 3T3L1 cells. This study shows that BPA induces epigenetic changes in a key adipogenic gene. These modifications are reversible and do not affect preadipocyte commitment and/or differentiation. We identify an alternative transcriptional mechanism by which BPA affects gene expression and demonstrate how the challenge of preventing exposure is fundamental for human health.

Aims: Methylsulfonylmethane (MSM), is an organosulfur compound, has many health benefits. Bisphenol-A (BPA) and γ-radiation (R) are two risky environmental contaminants that human beings are exposed to in everyday life. This work aims at unveiling the modulatory role of MSM in combating BPA and R co-exposure induced neurodegenerative disorder (Alzheimer's (AD)-mimic neurotoxicity)., Main Methods: Female rats were randomly divided into five groups. One group was normal control and the other four groups were subjected to subacute BPA intoxication and/or exposed to fractionated weekly doses of R for 4 weeks and either untreated or treated with MSM concomitantly., Key Findings: BPA and R co-exposure induced typical hallmarks of neurodegenerative disorders as revealed by tremendously elevated oxidative stress, extensive neuroinflammation (tumor necrosis factor -α and interleukin-1β), elevated AD markers (amyloid-beta (Aβ 42 ), acetylcholinesterase (AchE) activity and tau-phosphorylation) in cortex and hippocampus as well as up-regulation of microglial pro-inflammatory triggering receptor expressed on myeloid cell-2(TREM-2)/DNAX-activating protein of 12 kDa (DAP-12)/spleen-tyrosine kinase (Syk) pathway and its downstream targets (PLC-γ/DAG/p38-MAPK) in hippocampus. Also, neurodegenerative lesions were revealed in histopathological examination of cortex and hippocampus coupled with marked Aβ deposition in hippocampus. Whereas, MSM treatment improved histopathological insults and ameliorated level of oxidative stress, neuroinflammation and AD markers as well as modulated TREM-2/DAP-12/Syk pathway., Significance: Our data suggest that MSM afforded neuroprotection against BPA and R; supporting its potential application in the associated neurodegenerative disorders., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bisphenol-A (BPA) is one of the extensively studied estrogenic endocrine disrupting chemicals (EDC) with ubiquitous exposure among humans and wildlife. While there are literature reporting the association of dysregulated Brain-derived neurotrophic factor (BDNF) expression levels with altered cognitive and emotional behaviour such as anxiety-like and stress behaviour in animal models, there are no studies in BPA that investigate these altered neurobehavioural outcomes in parallel with the expression of intracellular proteins involved in BDNF signaling pathway. In this study, pregnant Wistar rats were exposed to BPA through water (25 μg/L, 250 μg/L, and 2.5 mg/L) during gestation day (GD) 9-21. Prenatal BPA exposure, increased anxiety-like behaviour in males and decreased exploratory behaviour in both male and female offspring. Downregulation of both BDNF and CYP19A1 genes were observed in male BPA-exposed offspring, whereas in females, the expression was upregulated. The expression of p-AKT, p-MEK and p-ERK proteins were increased in males, while in females, it decreased. Both the male and the female BPA-exposed offspring exhibited elevated levels of DNMT1 protein. The sex-specific alteration in the expression of CYP19A1 and DNA methyltransferase 1 (DNMT1) suggests that both hormonal and epigenetic dysregulation could underlie the long-term BPA-induced effect on anxiety-like behaviour in the offspring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats' lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.

Bisphenol-A (BPA) is a synthetic chemical used in the manufacturing of polycarbonates and epoxy resins. This paper is a review of studies reporting the occurrences and concentrations of BPA in the environment and associated impact on human health. Studies have found that at high temperature conditions such as open burning of dumped waste in developing nations can relocate BPA from plastic waste into the environment. BPA is a proven endocrine disruptor capable of mimicking or blocking the receptors and altering hormone concentrations and its metabolism. Even though it is consumed in a low dose, it can stimulate cellular responses and affect body functions. Biomonitoring studies show that human and animal exposure to BPA is rapid and continuous. In-depth studies are needed to understand the fate of these compounds particularly in the developing nations and the associated adverse health impacts of BPA due to prolonged exposure.

CNS myelination process involves proliferation and differentiation of oligodendrocyte progenitor cells (OPCs). Defective myelination causes onset of neurological disorders. Bisphenol-A (BPA), a component of plastic items, exerts adverse effects on human health. Our previous studies indicated that BPA impairs neurogenesis and myelination process stimulating cognitive dysfunctions. But, the underlying mechanism(s) of BPA induced de-myelination and probable neuroprotection by curcumin remains elusive. We found that curcumin protected BPA mediated adverse effects on oligosphere growth kinetics. Curcumin significantly improved proliferation and differentiation of OPCs upon BPA exposure both in-vitro and in-vivo. Curcumin enhanced the mRNA expression and protein levels of myelination markers in BPA treated rat hippocampus. Curcumin improved myelination potential via increasing β-III tubulin-/MBP + cells (neuron-oligodendrocyte co-culture) and augmented fluoromyelin intensity and neurofilament/MBP + neurons in vivo. In silico docking studies suggested Notch pathway genes (Notch-1, Hes-1 and Mib-1) as potential targets of BPA and curcumin. Curcumin reversed BPA mediated myelination inhibition via increasing the Notch pathway gene expression. Genetic and pharmacological Notch pathway inhibition by DAPT and Notch-1 siRNA exhibited decreased curcumin mediated neuroprotection. Curcumin improved BPA mediated myelin sheath degeneration and neurobehavioral impairments. Altogether, results suggest that curcumin protected BPA induced de-myelination and behavioural deficits through Notch pathway activation., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Puberty is a crucial developmental period for structural modifications of brain and activation of the neural circuits underlying sex differences in social behavior. It is possible that pubertal exposure to bisphenol-A (BPA), a common EED with a weak estrogenic activity, influences social behavior. After being exposed to BPA at 0.04, 0.4, 4 mg kg -1 for 18 days, the 7-week-old male mice were tested with social play and three-chamber. The results showed that pubertal BPA exposure decreased social play between adolescent males and sociability of adolescent males. Further, pubertal BPA exposure reduced sociability and inhibited social novel preferences of adult males. BPA inhibited social interactions with opposite sex but improved socio-sexual exploration and the low-intensity mating behavior (mounting) with same sex in adult males. In residential-intruder test, BPA-exposed adult males showed a decrease in aggressiveness and an enhancement in prosocial behavior with intruder. Western blot analysis showed that BPA (especially at 4 mg/kg/d) down-regulated the levels of AR in the amygdala and the striatum but up-regulated the levels of DR1 and DAT proteins in the striatum of adult males. BPA at 4 mg kg -1 decreased the levels of T in the serum and the brain. These results suggest that pubertal BPA exposure affects social play and sociability of adolescent males and even results in long-term effects on social behavior of adult males. BPA-induced down-regulations of the levels of AR in the amygdala and the striatum and up-regulation of the levels of DR1 and DAT in the striatum may be involved., Competing Interests: Declaration of competing interest All authors have no conflicts of interest including any financial to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Bisphenol-A, an organic synthetic compound, has been present in many consumer plastic products and food packaging since the 1960s. Nowadays, Bisphenol-A is widely used in the field of dentistry for the manufacturing of resin materials. Several studies have suggested that Bisphenol-A may cause adverse health effects due to its ability to act as an endocrine disruptor chemical which has raised concerns about its widespread use. The aim of this study is to present an overview of the research studies dealing with Bisphenol-A exposure in the field of dentistry. PubMed, Scopus, EMBASE, Europe PMC, Web of Science and reference lists of relevant papers were searched to identify articles for inclusion. Two authors screened literature and extracted data from included studies independently. The evidence supports that Bisphenol A is used in many fields of routine clinical dental practice such as restorative dentistry and orthodontics. Regarding Bisphenol-A exposure from dental materials, the current data concludes that is below the Tolerable Daily Intake levels, but further evaluation is needed to reveal any possible adverse events caused by low-dose BPA exposure., (Copyright© 2020 Dennis Barber Ltd.)

Bisphenol A (BPA) is a contaminant in virtually all Americans. To examine BPA's adverse effects, the FDA-NCTR, NIEHS, and 14 groups of academic scientists formed a consortium: CLARITY-BPA. The purpose of our study was to investigate the effects of a wide range of doses of BPA on fetal development of the NCTR CD-SD male rat urogenital sinus (UGS). Pregnant rats were administered BPA or positive control ethinylestradiol (EE2) daily, via oral gavage, from gestational day 6 through parturition. Tissues were collected on postnatal day 1 and the UGS was analyzed using computer-assisted 3-D reconstruction. Importantly, only low doses of BPA, as well as EE2, significantly changed birth weight and UGS morphology, including an increased size of the colliculus and decreased size of the urethra, consistent with prior reported BPA and EE2 effects. Our findings provide further evidence that BPA mediates nonmonotonic developmental effects on the fetal urogenital sinus., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The adsorption of bisphenol-A (BPA) on ordered mesoporous carbon (CMK-3) and modified CMK-3 (MCMK-3) for decontamination of aqueous medium was investigated. The CMK-3 and MCMK-3 materials had uniform pore sizes of 3.60 and 3.70 nm and high Brunauer-Emmett-Teller (BET) surface areas of 751 and 564 m 2  g -1 , respectively. The maximum adsorption capacities of CMK-3 and MCMK-3 were 178.57 (0.24 mg m -2 ) and 238.01 (0.42 mg m -2 ) mg g -1 , respectively at 298 K (pH 6.4). The difference in the adsorption capacities is attributed to the specific surface area and hydrophobicity of the adsorbents. The adsorption of BPA on CMK-3 and MCMK-3 may be influenced by π-π bonding and hydrophobic and electrostatic interactions, and the excellent adsorption capacity of MCMK-3 is attributed to its unique sp2-hybridized single-atom-layer structure. The kinetics and isotherm data were described by the pseudo-second order kinetic model and the Langmuir isotherm, respectively. This difference in the adsorption kinetics of CMK-3 and MCMK-3 is caused by the increase in the pore diameter of the latter. Further, CMK-3 and MCMK-3, with an open geometry consisting of interlinked nanorods, allow for faster intraparticle diffusion. Overall, CMK-3 and MCMK-3 could be promising adsorbents for the removal of chemicals containing benzene rings from wastewater., (Copyright © 2019. Published by Elsevier Ltd.)

The chemical industrial zone located along the Xiaoqing River wetlands adjacent to Bohai Sea is one of the largest production bases for brominated flame retardants in China. Herein, high levels of bisphenol-A, tetrabromobisphenol-A (TBBPA), tribromobisphenol-A, dibromobisphenol-A, and monobromobisphenol-A were detected in sediment, soil, and water samples of this zone in the range of below method detection limit (6  ng/kg dw, 4  ng/kg dw, and 2  ng/L, respectively. They were mainly buried in sediments as their highest levels in sediment samples. The small concentration fluctuation between water samples retrieved in the upstream and downstream zones is likely attributed to seawater backflow. The nearby chemical factories were point pollution sources and the less brominated analogs are largely from debromination of TBBPA. High pollution levels and the ecological risks of these pollutants along the Xiaoqing estuary to Bohai Sea need to be further assessed in future studies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA) is a ubiquitously distributed endocrine disrupting chemical (EDC). BPA exposure in humans has been a matter of concern due to its increased application in the products of day to day use. BPA has been reported to cause toxicity in almost all the vital organ systems even at a very low dose levels. It crosses the blood brain barrier and causes neurotoxicity. We studied the effect of BPA on the cerebral cortex of C57BL/6J mice and examined whether BPA exposure alters the expression of axonal and myelin structural proteins. Male mice were dosed orally to 40 μg and 400 μg BPA/kg body weight for 60 days. BPA exposure resulted in memory loss, muscle coordination deficits and allodynia. BPA exposure also caused degeneration of immature and mature oligodendrocytes as evaluated by decreased mRNA levels of 2',3'-cyclic nucleotide 3' phosphodiesterase (CNPase), nestin, myelin basic protein (MBP) and myelin-associated glycoprotein-1 (MAG-1) genes revealing myelin related pathology. It was observed that subchronic BPA exposure caused neuroinflammation through deregulation of inflammatory cytokines mRNA and protein expression which further resulted into neurotoxicity through axonal as well as myelin degeneration in the brain. BPA also caused increased oxidative stress in the brain. Our study indicates long-term subchronic low dose exposure to BPA has the potential to cause axonal degeneration and demyelination in the oligodendrocytes and neurons which may have implications in neurological and neuropsychological disorders including multiple sclerosis (MS), neuromyelitis optica and others., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The dramatic rise in obesity and metabolic syndrome can be related, at least in part, to environmental chemical factors such as Bisphenol-A (BPA). In this study, we aimed to understand the effects of low-dose Bisphenol-A on the human mature adipocytes and stromal vascular fraction (SVF) cells, obtained from subcutaneous mammary adipose tissue of overweight female patients, undergoing surgical mammary reduction. 24 and/or 48-h exposure to BPA 0.1 nM elicited significant increase of the inflammatory molecules interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemo-attractant protein 1α (MCP1α) and induced G protein-coupled estrogen receptor 30 (GPR30) levels more than two-fold both in mature adipocytes and SVF cells. These effects were similar to that obtained in the presence of GPR30-specific agonist G1 (100 nM) and were reverted by G15 (1 µM), a GPR30-selective antagonist. As a result of BPA-GPR30 signaling activation, fatty acid synthase (FAS) and leptin mRNA levels were significantly higher upon BPA exposure (P < 0.05) in mature adipocytes, with an opposite effect on adiponectin (ADIPOQ). In addition, an increase in SVF cell proliferation and ERK1/2 phosphorylation, was observed, compared to untreated cells. G15 reverted all of these effects. Interestingly, the action of BPA on SVF cell growth was mimicked by IL-8 treatment and was reverted by incubation with anti-IL8 antibodies. All these data suggest that BPA at 0.1 nM, a ten times lower concentration than environmental exposure, increases the expression of pro-inflammatory cytokines via GPR30 both in mature mammary adipocytes and in SVF cells with a possible involvement of IL-8.

Bisphenol-A (BPA) is a potential endocrine disruptor besides being associated with oxidative damage in several vertebrate classes. In the present study we investigated oxidative effects in erythrocytes and sperm cells as well as spermatic quality in Danio rerio exposed to 14 days at BPA concentrations of 2, 10 and 100 μg/L. Organelles structure, reactive species of oxygen (ROS) and lipoperoxidation (LPO) on erythrocytes and sperm cells were measured by flow cytometry and spermatic parameters were analyzed by the computer-assisted sperm analysis (CASA) system. For both cell types, when compared with control BPA treatment induced a significant increase in ROS and LPO production causing the membrane fluidity disorder, loss of membrane integrity and mitochondrial functionality. Furthermore, it was found a significant increase in DNA fragmentation in erythrocytes of zebrafish BPA exposed. Regarding the spermatic quality, results showed lower sperm motility in animals exposed to BPA, and alterations on velocity parameters of spermatozoa. Thus, the present study concludes that BPA affects the oxidative balance of both cell types, and that can directly affects the reproductive success of the adult Danio rerio. The sensitivity of erythrocytes to oxidative damage induced by BPA was similar to sperm cells, indicating a potential use of blood cells as indicators of oxidative damage present in fish sperm.

Steroids play an integral role in orchestrating embryonic development, and they can affect a suite of phenotypic traits, including learning and behavior. Endocrine disrupting compounds (EDCs) can alter steroid-dependent phenotypic traits during embryonic development. Bisphenol-A (BPA) is an EDC that disrupts the action of estrogen, and recent work indicates that BPA can affect learning and behavior similarly to estrogen. We exposed red-eared slider turtle (Trachemys scripta) eggs to BPA during embryonic development and tested hatchlings for effects on learning and behavior in modified T-mazes over the course of two weeks. We found that behavioral patterns changed within a day and over the course of the experiment, but we found no effect of BPA treatment. Further, we found that hatchling turtles were highly consistent in their behaviors. These behaviors varied among individuals, suggesting that there are discrete behavioral types in T. scripta hatchlings. The highly repetitive nature of behaviors in the hatchlings might explain the innate biases that we observed and warrants further study., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although Bisphenol-A (BPA) has been found to exhibit toxicological properties such as genotoxicity and oxidative stress, yet there is very little data available on its analogues. Since the replacement of BPA by its analogues, their presence has been found to increase in the environment leading to increased human exposure that makes it essential to investigate their toxic effects. Therefore, we explored the genotoxic and oxidative potential of two common BPA analogues, Bisphenol-B (BPB) and Bisphenol-F (BPF). Both analogues were found to induce cytotoxicity in human peripheral blood cells. They also caused an increase in reactive oxygen species levels leading to a decrease in GSH and an increase in LPO levels. Comet assay also suggested them to be genotoxic. Therefore, bisphenols were found capable of inducing cytotoxicity via oxidative stress and genotoxicity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background Bisphenol-A (BPA) is a widespread pollutant whose effects on pregnant women are poorly understood. Therefore, we investigated the effects of BPA on basal and bacteria-stimulated production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6], anti-inflammatory mediators [soluble glycoprotein 130 (sgp) 130, heme oxidase-1 (HO-1) and IL-10] and biomarkers for neurodevelopment [brain-derived neurotrophic factor (BDNF)], and oxidative stress [8-isoprostane (8-IsoP)] by the placenta. Methods Placental explant cultures were treated with BPA (0-10,000 nM) in the presence or absence of 107 colony-forming unit (CFU)/mL heat-killed Escherichia coli for 24 h. Biomarker concentrations in conditioned medium were quantified by the enzyme-linked immunosorbent assay (ELISA). Results Under basal conditions, IL-1β and IL-6 production was enhanced by BPA in a dose-dependent manner. Sgp130, a soluble receptor that reduces IL-6 bioactivity, was suppressed by BPA at 1000-10,000 nM. BPA also enhanced BDNF production at 1000 and 10,000 nM, and 8-IsoP expression at 10 and 100 nM. For bacteria-treated cultures, BPA increased IL-6 production at 100 nM and reduced sgp130 at 1000 nM but had no effect on IL-1β, TNF-α, BDNF, HO-1, 8-IsoP or IL-10 production. Conclusion BPA may increase placental inflammation by promoting IL-1β and IL-6 but inhibiting sgp130. It may also disrupt oxidative balance and neurodevelopment by increasing 8-IsoP and BDNF production.

Aims/hypothesis: Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical that has been associated with type 2 diabetes development. Low doses of BPA modify pancreatic beta cell function and induce insulin resistance; some of these effects are mediated via activation of oestrogen receptors α (ERα) and β (ERβ). Here we investigated whether low doses of BPA regulate the expression and function of ion channel subunits involved in beta cell function., Methods: Microarray gene profiling of isolated islets from vehicle- and BPA-treated (100 μg/kg per day for 4 days) mice was performed using Affymetrix GeneChip Mouse Genome 430.2 Array. Expression level analysis was performed using the normalisation method based on the processing algorithm 'robust multi-array average'. Whole islets or dispersed islets from C57BL/6J or oestrogen receptor β (ERβ) knockout (Erβ -/- ) mice were treated with vehicle or BPA (1 nmol/l) for 48 h. Whole-cell patch-clamp recordings were used to measure Na + and K + currents. mRNA expression was evaluated by quantitative real-time PCR., Results: Microarray analysis showed that BPA modulated the expression of 1440 probe sets (1192 upregulated and 248 downregulated genes). Of these, more than 50 genes, including Scn9a, Kcnb2, Kcnma1 and Kcnip1, encoded important Na + and K + channel subunits. These findings were confirmed by quantitative RT-PCR in islets from C57BL/6J BPA-treated mice or whole islets treated ex vivo. Electrophysiological measurements showed a decrease in both Na + and K + currents in BPA-treated islets. The pharmacological profile indicated that BPA reduced currents mediated by voltage-activated K + channels (K v 2.1/2.2 channels) and large-conductance Ca 2+ -activated K + channels (K Ca 1.1 channels), which agrees with BPA's effects on gene expression. Beta cells from ERβ -/- mice did not present BPA-induced changes, suggesting that ERβ mediates BPA's effects in pancreatic islets. Finally, BPA increased burst duration, reduced the amplitude of the action potential and enlarged the action potential half-width, leading to alteration in beta cell electrical activity., Conclusions/interpretation: Our data suggest that BPA modulates the expression and function of Na + and K + channels via ERβ in mouse pancreatic islets. Furthermore, BPA alters beta cell electrical activity. Altogether, these BPA-induced changes in beta cells might play a role in the diabetogenic action of BPA described in animal models.

Bisphenol-A (BPA) is a representative exogenous endocrine disruptor, which is extensively composed in plastic products. Due to the capability of passing through the blood-brain barrier, evidence has linked BPA exposure with multiple neuropsychological dysfunctions, neurobehavioral disorders and neurodegenerative diseases. However, the underlying mechanism by which BPA induces neurodegeneration still remains unclear. Our study used human embryonic stem cells-derived human cortical neurons (hCNs) as a cellular model to investigate the adverse neurotoxic effects of BPA. hCNs were treated with 0, 0.1, 1 and 10 μM BPA for 14 days. Impacts of BPA exposure on cell morphology, cell viability and neural marker (MAP2) were measured for evaluating the neurodegeneration. The intracellular calcium homeostasis, reactive oxygen species (ROS) generation and organelle functions were also taken into consideration. Results revealed that chronic exposure of BPA damaged the neural morphology, induced neuronal apoptosis and decreased MAP2 expression at the level of both transcription and translation. The intracellular calcium levels were elevated in hCNs after BPA exposure through NMDARs-nNOS-PSD-95 mediating. Meanwhile, BPA led to oxidative stress by raising the ROS generation and attenuating the antioxidant defense in hCNs. Furthermore, BPA triggered ER stress and increased cytochrome c release by impairing the mitochondrial function. Ultimately, BPA triggered the cell apoptosis by regulating Bcl-2 family and caspase-dependent signaling pathway. Taken together, BPA exerted neurotoxic effects on hCNs by eliciting apoptosis, which might due to the intracellular calcium homeostasis perturbation and cell organellar dysfunction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There is a striking interaction of genes and environment in the etiology of type 2 diabetes mellitus (T2DM). While endocrine disrupting chemicals (EDCs) like bisphenol-A (BPA) have received special attention for their mechanistic role in metabolic disruption, there is a lack of clinically relevant data on BPA levels in Asian Indians, a population which is more susceptible to type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Therefore, we measured systemic levels of BPA in patients with T2DM compared to individuals with normal glucose tolerance (n = 30 each). Serum BPA levels were estimated using ELISA kit, and biochemical determinations were done by standard protocols. Peripheral blood mononuclear cells (PBMCs) were used to profile the gene expression alterations with special reference to inflammation, estrogen receptors, and cellular senescence in these subjects. Serum levels of BPA were significantly higher in patients with T2DM compared to control individuals and positively correlated to poor glycemic control and insulin resistance. Patients with T2DM exhibited significantly elevated mRNA levels of senescence (GLB1, p16, p21, and p53) and inflammatory (IL6 and TNF-α) markers, shortened telomeres as well as elevated levels of estrogen-related receptor gamma (ERRγ), a recently identified receptor for BPA. BPA levels were positively correlated to senescence indicators, inflammatory markers and ERRγ and negatively correlated to telomere length. Our study is the first data in the clinical diabetes setting to demonstrate an association of increased BPA levels with cellular senescence, proinflammation, poor glycemic control, insulin resistance, and shortened telomeres in patients with T2DM.

Bisphenol-A is widely used chemical in industry and unfortunately often detected in natural waters. Considered as an emerging pollutant, bisphenol-A represents an environmental problem due to its endocrine-disrupting behavior. The production of activated carbon from alternative precursors has shown to be attractive in the removal of emerging pollutants from the water. Activated carbon was produced from waste coffee by physical and chemical activation and applied in the removal of bisphenol-A. The samples were characterized by elemental analysis, scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and analysis of textural properties. Bisphenol-A adsorption experiments showed that the chemically activated carbon was more efficient due to its high specific surface area (1039 m 2 /g) compared to the physically activated carbon (4.0 m 2 /g). The bisphenol-A adsorption data followed the pseudo-second-order model and Langmuir isotherm, which indicated a maximum adsorption capacity of 123.22 mg/g for chemically activated carbon. The results demonstrated a potential use of the coffee grounds as a sustainable raw material for the production of chemically activated carbon that could be used in water treatment.

In this study, highly porous N/S doped magnetic carbon aerogel (N/S-MCA) was successfully fabricated using sugarcane bagasse based cellulose and used for the removal of bisphenol‑A (BPA) from aqueous solution. The fabricated N/S-MCA nanocomposite derived from cellulose was characterized by various analytical techniques and supports the formation of the N/S-MCA in good yield and high purity. The batch adsorption studies were used for the adsorption of BPA onto N/S-MCA. The maximum removal of the BPA (98-99%) by the N/S-MCA was noted at pH 7, temperature 343 K, and initial BPA concentration of 100 ppm. The adsorption process followed pseudo-second-order reaction kinetics, as well as Langmuir isotherms. The thermodynamic parameters of the adsorption (the Gibbs free energy, entropy, and enthalpy) supported the spontaneity of the adsorption process. The results revealed that the mechanism on the synergistic adsorption between N/S doped magnetic carbon aerogel and BPA will therefore be an important guideline to design a carbon based adsorbent for high-efficient adsorption of environmental pollutants., (Copyright © 2019. Published by Elsevier B.V.)

The present study was conducted to investigate the antioxidant, histomorphometric, histochemical, immunohistochemical, biochemical, and cytological effects of coenzyme Q10 (CoQ10) against bisphenol-A (BPA)-induced testicular toxicity in rats. A total of 40 adult male Wistar rats were divided into five equal groups. The control group remained untreated. The vehicle control group was administered corn oil (2 ml/kg/day), the BPA group was given BPA (100 mg/kg/day), the CoQ10 group was supplemented with CoQ10 (10 mg/kg/day), and the rats in the CoQ10-BPA group received CoQ10 (10 mg/kg/day) followed by BPA (100 mg/kg/day) 1 h later. The treatments were administered by oral gavage for 14 days. Results showed that the seminiferous tubule diameters (STDs) and seminiferous epithelium heights (SEHs) at stages VII-VIII and XII-XIV, number of undifferentiated embryonic cell transcription factor-1 (UTF-1) positive cells per tubule, UTF-1 positive tubules (%), plasma glutathione (GSH), and serum superoxide dismutase activities, testicular GSH activity and sperm viability (%) decreased whereas the number of terminal dUTP nick end labeling (TUNEL) positive cells per tubule, TUNEL positive tubules (%), testicular and serum malondialdehyde (MDA) levels, and the rate of mid-piece sperm abnormality increased in the BPA administered group. However, while the STDs at stages VII-VIII and XII-XIV, SEHs at stages VII-VIII, plasma GSH, and serum SOD activities increased, serum MDA level decreased in the CoQ10-BPA group. In conclusion, these results suggest a protective effect of CoQ10 against BPA-induced testicular toxicity in rats.

The aim was to evaluate the effect of perinatal BPA exposure of one or both parents on the implantation index and expression of talin, occludin and E-cadherin in the uterine epithelial cells (UEC) of the offspring. Pregnant Wistar dams (F0) received BPA or vehicle from gestational day (GD) 6 to lactation day 21. F1 animals were mated forming four groups: Control dam-Control sire (C♀-C♂), BPA dam -Control sire (B♀-C♂), Control dam -BPA sire (C♀-B♂), BPA dam -BPA sire (B♀-B♂). F1 dams were sacrificed at GD 6. Significantly decreased number of implantation sites was observed in the B♀-B♂ group as compared to the C♀-C♂ group, which correlated with decreased talin apical/basal expression ratio, occludin apical expression, and E-cadherin apical/lateral expression ratio in the UEC. Furthermore, decreased E-cadherin expression in the blastocyst was observed. Our data suggest that reduced protein expressions in F1 BPA offspring could result from decreased progesterone serum levels., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bisphenol-A (BPA) is a lipophilic, organic, synthetic compound that has been used as an additive in polycarbonate plastics manufacturing since 1957. Studies have shown that BPA interferes with the development and functions of the brain, but little is known about the effects of BPA on human glutamatergic neurons (hGNs) at the molecular and cellular levels. We investigated the impact of chronic exposure to BPA to hGNs derived from human embryonic stem cells (hESCs). The results showed that chronic exposure of different concentrations of BPA (0, 0.1, 1.0 and 10 μM) to hGNs for 14 days reduced neurite outgrowth in a concentration-dependent manner. Using presynaptic protein synaptophysin and postsynaptic protein PSD-95 antibodies, immunofluorescence staining and western blotting results indicated that BPA exposure altered the morphology of dendritic spines and increased synaptophysin and PSD-95 expression. Furthermore, BPA exposure at concentrations higher than 1.0 μM resulted in the increase of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression and deterioration of dendritic spines. In addition, our results suggested that these BPA mediated neurotoxicity effects were due to an increased production of reactive nitrogen species (RNS) and reactive oxygen species (ROS) via increased nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), 3-nitrotyrosine expression and Ca 2+ influx. These results imply that hESC-based neuronal differentiation is an excellent cellular model to examine BPA-induced neurotoxicity on human neurons at the cellular and molecular level., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Due to its endocrine disrupting nature Bisphenol-A (BPA), a chemical used in the plastic industry was placed under a ban which provided an incentive for its replacement by bisphenol and non-bisphenol based plasticizers. The use of bisphenol replacements in industry is increasing day by day. Therefore, it becomes prudent to put them under scrutiny. We studied the direct interaction of 45 BPA replacements and BPA with 12 nuclear receptors using an endocrine disruptome docking program (Kolšek et al., 2014b). Infact, the mechanism which could involve a direct interaction of ligands with nuclear receptors was taken into consideration. We found that the replacements, which were analogues of BPA, easily interacted with nuclear receptors due to the presence of phenyl moiety and their hydrophobic nature probably crucial for their endocrine disrupting potential. We therefore, strongly recommend reconsideration of BPA analogues in industries., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Intracellular Ca 2+ signaling plays an essential role in synaptic plasticity. This study examined the effect of BPA on concentration of intracellular Ca 2+ ([Ca 2+ ] i ) by measuring fluorescence intensity of Ca 2+ in hippocampal neurons in vitro. The results showed that BPA for 30 min exerted dose-dependently dual effects on glutamate-elevated [Ca 2+ ] i : BPA at 1-10 μM suppressed but at 1-100 nM enhanced glutamate-raised [Ca 2+ ] i . BPA-potentiated [Ca 2+ ] i was blocked by the antagonist of NMDA receptor and was eliminated by an estrogen-related receptor gamma (ERRγ) antagonist rather than an AR antagonist. Both inhibitors of MAPK/ERKs and MAPK/p38 blocked BPA-enhanced [Ca 2+ ] i . Co-treatment of BPA with 17β-E 2 or DHT eliminated the enhancement of 17β-E 2 , DHT, and BPA in glutamate-elevated [Ca 2+ ] i . These results suggest that BPA at nanomole level rapidly enhances Ca 2+ influx through NMDA receptor by ERRγ-mediated MAPK/ERKs and MAPK/p38 signaling pathways. However, BPA antagonizes both estrogen and androgen enhancing NMDA receptor-mediated Ca 2+ influx in hippocampal neurons., (Copyright © 2019. Published by Elsevier B.V.)

The retinoid system controls essential cellular processes including mitosis, differentiation and metabolism among others. Although the retinoid-signalling pathway is a potential target for the action of several endocrine disrupting chemicals (EDCs), the information about the developmental effects of bisphenol-A (BPA) on the hepatic retinoid system is scarce. Herein, male mice were in utero exposed to BPA following maternal subcutaneous doses of 0, 10 and 100 μg/kg bw/day from gestational day 9-16 and they were sacrificed at post-natal day 30. Retinoid concentrations and gene expression of key elements involved in the retinoid system were determined in liver. BPA increased all-trans-retinoic acid concentration and expression of Adh1, Aox1 and Cyp1a2 (biosynthesis of retinoic acid), while reduced Mrp3 (efflux from hepatocyte to blood), increased Bcrp expression (biliary excretion) and changed the retinoid-dependent signalling system after reducing expression of Rxrβ and increasing that of Fgf21. Furthermore, we found bivariate associations of Rarγ and Rxrγ expressions with all-trans-retinoic acid concentrations and of Fgf21 expression with that of Rarγ. Those findings occurred in animals which showed altered pancreatic function and impaired glucose metabolism during adulthood. The present information should be useful for enhancing testing methods for the identification of EDCs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The plasticizer bisphenol-A (BPA) is common to municipal wastewaters and can exert toxicity to exposed organisms in the environment. Here BPA concentration at 5 sewage treatment works (STW) and distribution throughout a river catchment in South West UK were investigated. Sampling sites included influent and effluent wastewater (n = 5), river water (n = 7) and digested sludge (n = 2) which were monitored for 7 consecutive days. Findings revealed average BPA loads in influent wastewater at two STWs were 10-37 times greater than the other wastewaters monitored. Concentrations up to ~100 μg L -1 were measured considerably higher than previously reported for municipal wastewaters. Temporal variability throughout the week (i.e., highest concentrations during weekdays) suggests these high concentrations are linked with industrial activity. Despite ≥90% removal during wastewater treatment, notable concentrations remained in tested effluent (62-892 ng L -1 ). However, minimal impact on BPA concentrations in river water was observed for any of the effluents. The maximum BPA concentration found in river water was 117 ng L -1 which is considerably lower than the current predicted no effect concentration of 1.6 μg L -1 . Nevertheless, analysis of digested sludge from sites which received these elevated BPA levels revealed average concentrations of 4.6 ± 0.3 and 38.7 ± 5.4 μg g -1 . These sludge BPA concentrations are considerably greater than previously reported and are attributed to the high BPA loading in influent wastewater. A typical sludge application regime to agricultural land would result in a predicted BPA concentration of 297 ng g -1 in soil. Further studies are needed on the toxicological thresholds of exposed terrestrial organisms in amended soils to better assess the environmental risk here., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The endocrine disruptor, Bisphenol-A (BPA), alters many behavioral and neural parameters in rodents. BPA administration to gonadally intact adolescent rats increases anxiety, impairs spatial memory, and decreases dendritic spine density when measured in adulthood. Since BPA's action seems to be mediated through gonadal steroid receptors, the current experiments were done in ovariectomized (OVX) female rats to examine the effects on behavior and spine density of adolescent BPA exposure under controlled hormone conditions. OVX (postnatal day, PND, 21) female Sprague-Dawley rats (n = 66) received subcutaneous injections of BPA (40 μg/kg/bodyweight), 17β-Estradiol (E2, 50 μg/kg/bodyweight), or saline during adolescence (PND 38-49). Following the last injection brains were processed for Golgi impregnation (Exp1), behavioral and spine density in adolescence (Exp2), or in adulthood (Exp3). In Exp1, E2 increased spine density in CA1 pyramidal cells and BPA decreased spine density in granule cells of the dentate gyrus (DG). In Exp2, BPA impaired spatial memory on the object placement (OP) task, E2 increased spine density in CA1, BPA decreased spine density in the DG and the medial prefrontal cortex (mPFC). When measured in adulthood (Exp3), BPA impaired OP and object recognition (OR) performance, E2 increased spine density in CA1, and BPA decreased spine density in CA1, the mPFC and the DG. Results provide novel data on the effects of adolescent BPA in an OVX model and are compared to data in intact animals and within the context of understanding the importance of the profound neuronal alterations occurring during adolescent development., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background & Objectives: Bisphenol-A (BPA) and phthalates are utilized widely in consumer products. Due to their ubiquitous presence in the environment, a concern is expressed worldwide about their possible effect on human reproductive health. This study was conducted to compare the internal exposure of BPA and phthalates (using their metabolites as biomarkers) in plasma samples of infertile and fertile women., Methods: A sensitive gas chromatographic-mass spectrometric (GC-MS) method was developed to simultaneously quantify BPA and four phthalate monoester metabolites [namely mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)] in human plasma. The method was validated using charcoal-stripped human plasma. Activated charcoal was also utilized to reduce contamination from reagents. The method was designed to account for and/or eliminate background contamination from all sources., Results: The limit of quantification for the method was 5 ng/ml for MMP and MBzP, while 1 ng/ml for BPA, MEHP and MEHHP, respectively. The precision and accuracy were well within the acceptable range. BPA was detectable in 77 per cent of plasma samples of infertile women and 29 per cent of fertile women. All the four phthalate metabolites were detected in plasma samples of both fertile and infertile women., Interpretation & Conclusions: A GC-MS was developed and validated to estimate the BPA and four phthalate monoester metabolites in human plasma. It was utilised to analyse the plasma samples from fertile and infertile women. The infertile women showed significantly higher plasma concentrations of MBzP, BPA and MEHHP as compared to fertile women. The levels of MMP and MEHP were not significantly different between the two groups. Further studies need to be done to confirm these preliminary findings., Competing Interests: None