Effects Of Bisphenol A Research Articles

The effect of bisphenols on sex and thyroid hormone concentrations in cord blood among newborns

This study aims to investigate the associations of bisphenols with sex and thyroid hormones in cord blood among newborns. Four bisphenols, three hormones related to gonadal function, and four parameters related to thyroid function were measured in umbilical cord blood in 378 mother-newborn pairs. Multivariable linear regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression were used. In the multivariable linear regression, bisphenol A (BPA) was associated with increased testosterone (TT) (regression coefficient, β = 0.049, 95% confidence interval, CI: 0.013,0.085; p = 0.007) and free tri-iodothyronine (FT3) levels (β = 0.019, 95% CI: 0.003, 0.035; p = 0.023), and decreased thyroid peroxidase antibody (TPOAb) (β = −0.053, 95% CI: 0.098, −0.008; p = 0.021). Consistently associations were observed in males, except TT, which was observed in females, and bisphenol AF (BPAF) was associated with decreased follicle-stimulating hormone (FSH) in females. These associations were also observed in a mixture of bisphenols. Moreover, we observed maternal prepregnancy body mass index (BMI) and delivery mode disparity in the relationship between bisphenols and sex and thyroid hormones. This study suggests that bisphenols may exert effects on sex and thyroid hormones in newborns, the effect may vary with sex differences, maternal prepregnancy BMI, and delivery mode.

Unveiling the intricacies of BPA and BPS: comprehensive insights into its toxic effects using a cutting-edge microphysiological system

Concerns over Bisphenol A (BPA) and its substitute, Bisphenol S (BPS), have led to innovative exploration due to potential adverse health effects. BPS, replacing BPA in some regions to avoid toxic impacts, remains insufficiently studied. Besides this, the organ-on-a-chip technology emerges as a transformative solution in drug discovery and chemiclas toxicity testing, minimizing costs and aligning with ethical standards by reducing reliance on animal models, by integrating diverse tissues and dynamic cell environments enhances precision in predicting organ function.Here, we employ a 3-organ-on-a-chip microfluidic device with skin, intestine, and liver cultures to assess the effects of BPA and BPS via topical and oral administration. Our evaluation focused on gene markers associated with carcinogenicity, systemic toxicity, and endocrine disruption. BPA exhibited expected absorption profiles, causing liver injury and genetic modulation in related pathways. BPS, a safer alternative, induced adverse effects on gene expression, particularly in topical absorption, with distinct absorption patterns. Our findings underscore the urgency of addressing BPA and BPS toxicity concerns, highlighting the crucial role of organ-on-a-chip technology in understanding associated health risks. The study promotes the organ-on-a-chip methodology as a valuable tool for safe drug development and disease treatments, offering a novel liver toxicity screening alternative to traditional animal tests. This contributes to advancing comprehension of the biological effects of these compounds, fostering improved safety assessments in human health.

VD3/VDR attenuates bisphenol A-induced impairment in mouse Leydig cells via regulation of autophagy.

Bisphenol A (BPA) is an endocrine disruptor with reproductive toxicity. Further, 1,25-dihydroxyvitamin D3 (VD3) plays an important role in male reproduction by binding vitamin D receptor (VDR) and mediating the pleiotropic biological actions that include spermatogenesis. However, whether VD3/VDR regulates the effect of BPA on Leydig cells (LCs) injury remains unknown. This study aimed to explore the effects of VD on BPA-induced cytotoxicity in mouse LCs. Hereby, LCs treated with BPA, VD3, or both were subjected to the assays of cell apoptosis, proliferation, autophagy, and levels of target proteins. This study unveiled that cell viability was dose-dependently reduced after exposure to BPA. BPA treatment significantly inhibited LC proliferation, induced apoptosis, and also downregulated VDR expression. By jointly analyzing transcriptome data and Comparative Toxicogenomics Database (CTD) data, autophagy signaling pathways related to testicular development and male reproduction were screened out. Therefore, the autophagy phenomenon of cells was further detected. The results showed that BPA treatment could activate cell autophagy, Vdr-/- inhibits cell autophagy, and active VD3 does not have a significant effect on the autophagy of normal LCs. After VD3 and BPA were used in combination, the autophagy of cells was further enhanced, and VD3 could alleviate BPA-induced damage of LCs. In conclusion, this study found that supplementing VD3 could eliminate the inhibition of BPA on VDR expression, further enhance LCs autophagy effect, and alleviate the inhibition of LCs proliferation and induction of apoptosis by BPA, playing a protective role in cells. The research results will provide valuable strategies to alleviate BPA-induced reproductive toxicity.

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

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

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

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

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

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

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

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

Disruption of functions of primary human neonatal melanocytes cultured in the presence of bisphenol A and its analogs bisphenol F and bisphenol S

Bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS) are contaminants of emerging concern (CECs) that humans are exposed to. In silico and zebrafish studies have linked BPA, BPF, and BPS exposure to pigmentation abnormalities, but no studies have examined their impact on primary human melanocytes. Herein, we examined the effects of BPA, BPF, and BPS exposure using human epidermal neonatal melanocytes. BPA induced the greatest cytotoxicity, followed by BPS, whereas BPF did not affect viability. BPA did not alter cellular melanin, whereas BPF and BPS diminished it at 100 µM. BPA decreased dendricity, as did BPF and BPS, although BPF was a potent suppressor of dendricity than BPS. BPA inhibited tyrosinase activity, followed by BPF, while BPS weakly suppressed tyrosinase activity. The tyrosinase activity was mostly recovered after the cessation of bisphenol treatments, although it remained lower for BPA and BPF. All bisphenols elevated cellular ROS production, although BPA and BPS showed non-monotonic dose responses. BPA and BPS augmented IL-6 cytokine secretion in melanocyte cultures treated with lipopolysaccharide, but BPF did not, suggesting that they exacerbate melanocyte inflammation. Collectively, these findings indicate BPA, BPF, and BPS, may impair melanocyte function and pose health hazards, warranting more study.

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

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

Developmental programming: An exploratory analysis of pancreatic islet compromise in female sheep resulting from gestational BPA exposure

Developmental exposure to endocrine disruptors like bisphenol A (BPA) are implicated in later-life metabolic dysfunction. Leveraging a unique sheep model of developmental programming, we conducted an exploratory analysis of the programming effects of BPA on the endocrine pancreas. Pregnant ewes were administered environmentally relevant doses of BPA during gestational days (GD) 30–90, and pancreata from female fetuses and adult offspring were analyzed. Prenatal BPA exposure induced a trend toward decreased islet insulin staining and β-cell count, increased glucagon staining and α-cell count, and increased α-cell/β-cell ratio. Findings were most consistent in fetal pancreata assessed at GD90 and in adult offspring exposed to the lowest BPA dose. While not assessed in fetuses, adult islet fibrosis was increased. Collectively, these data provide further evidence that early-life BPA exposure is a likely threat to human metabolic health. Future studies should corroborate these findings and decipher the molecular mechanisms of BPA's developmental endocrine toxicity.

Cuscuta chinensis flavonoids alleviate ovarian damage in offspring female mice induced by BPA exposure during pregnancy by regulating the central carbon metabolism pathway

Pregnancy is a sensitive window period for bisphenol A (BPA) exposure. BPA can pass through the placenta and cause reproductive damage in offspring female mice. Even BPA that is not metabolized during lactation can be passed through milk. Cuscuta chinensis flavonoids (CCFs) can alleviate reproductive damage caused by BPA, but the mechanism of action is unclear. To investigate the potential mitigating impact of CCFs on ovarian damage resulting from BPA exposure during pregnancy, we administered BPA and CCFs to pregnant mice during the gestational period spanning from 0.5 to 17.5 days. Aseptic collection of serum and ovaries from female mice was conducted on postnatal day 21 (PND21). Serum hormone levels and tissue receptor levels were quantified utilizing ELISA and PCR, while ovaries underwent sequencing and analysis through transcriptomics and metabolomics techniques. Additionally, the assessment of ovarian oxidative stress levels was carried out as part of the comprehensive analysis. The results showed that CCFs administration mitigated the adverse effects induced by BPA exposure on ovarian index, hormone levels, receptor expression, and mRNA expression levels in female offspring mice. The joint analysis of transcriptome and metabolome revealed 48 enriched pathways in positive ion mode and 44 enriched pathways in negative ion mode. Among them, the central carbon metabolism pathway is significantly regulated by BPA and CCFs. The screened sequencing results were verified through qPCR and biochemical kits. In this study, CCFs may participate in the central carbon metabolism pathway by reducing the expression of Kit proto-oncogene (Kit), hexokinase 1 gene (Hk1) and pyruvate kinase M (Pkm) mRNA and increasing the expression of h-ras proto-oncogene (Hras), sirtuin 3 (Sirt3), sirtuin 6 (Sirt6) and TP53 induced glycolysis regulatory phosphatase gene (Tigar) mRNA, thereby resisting the effects of BPA on the body. At the same time, the metabolic levels of D-Fructose 1,6-bisphosphate and L-Asparagine tend to be stable. Moreover, CCFs demonstrated a capacity to diminish the BPA-induced escalation in reactive oxygen species (ROS) and malondialdehyde (MDA). Simultaneously, it exhibited the ability to elevate levels of glutathione (GSH) and catalase (CAT), thereby effectively preventing peroxidation. In summary, CCFs alleviate BPA-induced ovarian damage in offspring female mice by regulating the central carbon metabolism pathway. This study will improve the information on BPA reproductive damage antagonist drugs and provide a theoretical basis for protecting animal reproductive health.

Evaluation of the chronic toxicity of bisphenol A and bisphenol AF to sea cucumber Apostichopus japonicus after long-term single and combined exposure at environmental relevant concentration

Bisphenols are emerging endocrine disrupting pollutant, and several studies have reported that they are already ubiquitous in various environmental matrices and intend to deposit in sediment. The primary sources of bisphenols are river and sewage discharge. Sea cucumber (Apostichopus japonicus), a typical deposit feeder, is one of the most important commercial marine species in Aisa. However, the effects of the bisphenol A (BPA) and its analogues bisphenol AF (BPAF) on sea cucumber was unclear. In this study, we carried out field survey in major sea cucumber farming areas in northern China, with the aim of determining which bisphenol analogue is the major bisphenol contamination in this aquaculture area. The results showed that the presence of BPAF was detected in four sampling sites (Dalian, Tangshan, Laizhou, and Longpan). The mean level of BPAF in Laizhou sediment samples was the highest which reached to 9.007 ± 4.702 μ g/kg. Among the seawater samples, the BPAF only have been detected in the samples collected at Longpan. (0.011 ± 0.003 μ g/L). Furthermore, we conducted an experiment to evaluate the single and combined toxicity of BPA and BPAF on sea cucumbers. The concentrations were informed by the findings based on the results of field research. (0.1, 1.0, and 10 μ g/L). After exposure, the body weight gain, and specific growth rate showed no significant changes (P > 0.05). We observed the histological alterations in respiratory tree of treated sea cucumbers including the fusion and detachment of lining epithelial tissue, and increase of lumen space. However, the catalase (CAT), malondialdehyde (MDA), and glutathione (GSH) activity was not significantly changed (P > 0.05). We evaluated the effects of BPA and BPAF through calculating the integrated biomarker response index (IBR), and the results indicated that the toxicity of combined treatment was higher than single treatment. Additionally, BPAF exposure to A. japonicus was more toxic than BPA.

Investigation of the effects of p-Coumaric acid on MDA, some antioxidants and histopathological parameters in nephrotoxicity induced by bisphenol A in rats

The aim of this study was to investigate p-Coumaric acid (PCA) as a protector in detecting oxidative and targeted damage in the elongation tissue of rats induced by bisphenol A (BPA). BPA is an environmental pollutant widely used in many areas. The widespread use of this substance increases its transmission to humans. BPA causes damage to many tissues and organs. One of the most frequently damaged organs is the kidney. In this study, fifty healthy male rats were used to determine the effects of BPA and PCA. A total of five experimental groups were formed with ten animals in each group. Group 1 was set as the Control, Group 2 as BPA, Group 3 as BPA+PCA50, Group 4 as BPA+PCA100, and Group 5 as PCA100. The experiment lasted 14 days. Hematoxylin eosin staining and ELISA analyses were performed on kidney tissues at the end of the experiment. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and nitric oxide (NO) levels were determined in the kidney tissues by ELISA analysis. It was observed that kidney MDA and NO levels increased in the groups administered BPA while SOD and GSH levels decreased. Histopathologically, degeneration and necrosis in the tubular epithelium, glomerular atrophy, and hyperemia in the vessels were observed in the kidney tissues of the BPA groups. In the BPA+PCA groups it was seen that PCA prevented the negative effects of BPA in a dose-dependent manner, and helped in the maintenance of values close to the control group.

Molecular insights into the antioxidative and anti-inflammatory effects of P-coumaric acid against bisphenol A-induced testicular injury: In vivo and in silico studies

This study investigated the protective effects of p-coumaric acid (PCA) against bisphenol A (BPA)-induced testicular toxicity in male rats. The rats were divided into control, BPA, BPA+PCA50, BPA+PCA100, and PCA100 groups. Following a 14-day treatment period, various analyses were conducted on epididymal sperm quality and testicular tissues. PCA exhibited dose-dependent cytoprotective, antioxidant, and anti-inflammatory effects, ameliorating the decline in sperm quality induced by BPA. The treatment elevated antioxidant enzyme activities (SOD, GPx, CAT) and restored redox homeostasis by increasing cellular glutathione (GSH) and reducing malondialdehyde (MDA) levels. PCA also mitigated BPA-induced proinflammatory responses while reinstating anti-inflammatory IL-10 levels. Apoptotic parameters (p53 and p38-MAPK) were normalized by PCA in BPA-treated testicular tissue. Immunohistochemical and immunofluorescent analyses confirmed the cytoprotective and anti-inflammatory effects of PCA, evidenced by the upregulation of HO-1, Bcl-2, and Nrf-2 and the downregulation of the proapoptotic gene Bax in BPA-induced testicular intoxication. PCA corrected the disturbance in male reproductive hormone levels and reinstated testosterone biosynthetic capacity after BPA-induced testicular insult. In silico analyses suggested PCA's potential modulation of the oxidative stress KEAP1/NRF2/ARE pathway, affirming BPA's inhibitory impact on P450scc. This study elucidates BPA's molecular disruption of testosterone biosynthesis and highlights PCA's therapeutic potential in mitigating BPA's adverse effects on testicular function, showcasing its cytoprotective, anti-inflammatory, and hormone-regulating properties. The integrated in vivo and in silico approach offers a comprehensive understanding of complex mechanisms, paving the way for future research in reproductive health and toxicology, and underscores the importance of employing BPA-free plastic wares in semen handling.

Investigation of the role of curcumin against the toxicity induced by bisphenol a on the reproductive system in male rats

Bisphenol A (BPA) is an endocrine disruptor and an environmental pollutant; it can produce free radicals, which cause damage in various tissues. Curcumin has been demonstrated to help with a variety of male reproductive diseases, as well as to scavenge free radicals and function as an antioxidant. The aim is to estimate the protective role of Curcumin against the toxic effect of BPA in male rats by determining the levels of antioxidants and sexual hormones, before and after treatment with this herb. The effect of curcumin as a protective role against BPA on the oxidative stress parameters showed that Curcumin could decrease MDA concentration and at the same time increase the concentration of both catalase and SOD. Also, the results revealed that Curcumin could increase the concentration of LH, FSH, and testosterone as compared to the BPA-treated group.&#x0D;

Mechanistic interplay of dual environmental stressors: Bisphenol-A and cadmium-induced ovarian follicular damage and hepatocyte dysfunction in vivo

This study investigates the individual and combined toxic effects of Bisphenol A (BPA) and Cadmium (Cd) in zebrafish, recognizing the complex mixture of pollutants organisms encounter in their natural environment. Examining developmental, neurobehavioral, reproductive, and physiological aspects, the study reveals significant adverse effects, particularly in combined exposures. Zebrafish embryos exposed to BPA + Cd exhibit synergistically increased mortality, delayed hatching, and morphological abnormalities, emphasizing the heightened toxicity of the combination. Prolonged exposure until 10 days post-fertilization underscores enduring effects on embryonic development. BPA and Cd induce oxidative stress, as evidenced by increased production of reactive oxygen species and lipid peroxidation. This oxidative stress disrupts cellular functions, affecting lipid metabolism and immune response. Adult zebrafish exposed to BPA and Cd for 40 days display compromised neurobehavioral functions, altered antioxidant defenses, and increased oxidative stress, suggesting potential neurotoxicity. Additionally, disruptions in ovarian follicle maturation and skeletal abnormalities indicate reproductive and skeletal impacts. Histological analysis reveals significant liver damage, emphasizing the synergistic hepatotoxicity of BPA and Cd. Molecular assessments further demonstrate compromised cellular defense mechanisms, synaptic function, and elevated cellular stress and inflammation-related gene expression in response to combined exposures. Bioaccumulation analysis highlights differential tissue accumulation patterns. In conclusion, this study provides comprehensive insights into the multifaceted toxicological effects of BPA and Cd in zebrafish, raising concerns about potential adverse impacts on environmental ecosystems and human health.

Bisphenol A promotes cell death in healthy respiratory system cells through inhibition of cell proliferation and induction of G2/M cell cycle arrest.

Bisphenol A (BPA) is a substance that can harm the environment and human health by interfering with the normal functioning of the body's hormonal system. It is commonly found in various plastic-based products such as cosmetics, canned foods, beverage containers, and medical equipment and as well as it can also be absorbed by inhalation. There have been limited studies on the effects of BPA on lung fibroblasts, and it is still unclear how high levels of BPA can impact respiratory system cells, particularly the lungs and trachea. In this research, we aimed to investigate the cell cycle disruption potential of BPA on respiratory system cells by examining healthy trachea and lung cells together for the first time. The findings indicated that BPA exposure can alter the healthy cells' morphology, leading to reduced cellular viability that has been assessed by MTT and SRB assays. BPA treatment was able to activate caspase3 as expected, which could cause apoptosis in treated cells. Although the highest dose of BPA did not increase the apoptotic rate of rat trachea cells, it remarkably caused them to become necrotic (52.12%). In addition to quantifying the induction of apoptosis and necrosis by BPA, cell cycle profiles were also determined using flow cytometry. Thereby, BPA treatment unexpectedly inhibited the cell cycle's progression by causing G2/M cell cycle arrest in both lung and tracheal cells, which hindered cell proliferation. The findings of the study suggested that exposure to BPA could lead to serious respiratory problems, even respiratory tract cancers via alterations in the cell cycle.

Preliminary investigation into the impact of BPA on osteoblast activity and bone development: In vitro and in vivo models

Bisphenol A (BPA), an ingredient in consumer products, has been suggested that it can interfere with bone development and maintenance, whereas the molecule mechanism remains unclear. The objective of this study is to investigate the effect of BPA on early bone differentiation and metabolism, and its potential molecule mechanism by employing hFOB1.19 cell as an in vitro model, as well as larval zebrafish as an in vivo model. The in vitro experiments indicated that BPA decreased cell viability, inhibited osteogenic activity (such as ALP, RUNX2), increased ROS production, upregulated transcriptional or protein levels of apoptosis-related molecules (such as Caspase 3, Caspase 9), while suppressed transcriptional or protein levels of pyroptosis-specific markers (TNF-α, TNF-β, IL-1β, ASC, Caspase 1, and GSDMD). Moreover, the evidences from in vivo model demonstrated that exposure to BPA distinctly disrupted pharyngeal cartilage, craniofacial bone development, and retarded bone mineralization. The transcriptional level of bone development-related genes (bmp2, dlx2a, runx2, and sp7), apoptosis-related genes (bcl2), and pyroptosis-related genes (cas1, nlrp3) were significantly altered after treating with BPA in zebrafish larvae. In summary, our study, combining in vitro and in vivo models, confirmed that BPA has detrimental effects on osteoblast activity and bone development. These effects may be due to the promotion of apoptosis, the initiation of oxidative stress, and the inhibition of pyroptosis.

Bisphenol-A Abrogates Proliferation and Differentiation of C2C12 Mouse Myoblasts via Downregulation of Phospho-P65 NF-κB Signaling Pathway.

Previous studies showed that bisphenol-A (BPA), a monomer of polycarbonate plastic, is leached out and contaminated in foods and beverages. This study aimed to investigate the effects of BPA on the myogenesis of adult muscle stem cells. C2C12 myoblasts were treated with BPA in both proliferation and differentiation conditions. Cytotoxicity, cell proliferation and differentiation, antioxidant activity, apoptosis, myogenic regulatory factors (MRFs) gene expression, and mechanism of BPA on myogenesis were examined. C2C12 myoblasts exposed to 25-50 µM BPA showed abnormal morphology, expressing numerous and long cytoplasmic extensions. Cell proliferation was inhibited and was accumulated in subG1 and S phases of the cell cycle, subsequently leading to apoptosis confirmed by nuclear condensation and the expression of apoptosis markers, cleaved caspase-9 and caspase-3. In addition, the activity of antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase was significantly decreased. Meanwhile, BPA suppressed myoblast differentiation by decreasing the number and size of multinucleated myotubes via the modulation of MRF gene expression. Moreover, BPA significantly inhibited the phosphorylation of P65 NF-κB in both proliferation and differentiation conditions. Altogether, the results revealed the adverse effects of BPA on myogenesis leading to abnormal growth and development via the inhibition of phospho-P65 NF-κB.

Toxicity of low dose bisphenols in human iPSC-derived cardiomyocytes and human cardiac organoids – Impact on contractile function and hypertrophy

Bisphenol A (BPA) and its analogs are common environmental chemicals with various adverse health impacts, including cardiac toxicity. In this study, we examined the long term effect of low dose BPA and three common BPA analogs, bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) based models. HiPSC-CMs and human cardiac organoids were exposed to these chemicals for 4–5 or 20 days. 1 nM BPA, BPS, and BPAF, but not BPF, resulted in suppressed myocyte contractility, retarded contraction kinetics, and aberrant Ca2+ transients in hiPSC-CMs. In cardiac organoids, BPAF and BPA, but not the other bisphenols, resulted in suppressed contraction and Ca2+ transients, and aberrant contraction kinetics. The order of toxicities was BPAF > BPA>∼BPS > BPF and the toxicities of BPAF and BPA were more pronounced under longer exposure. The impact of BPAF on myocyte contraction and Ca2+ handling was mediated by reduction of sarcoplasmic reticulum Ca2+ load and inhibition of L-type Ca2+ channel involving alternation of Ca2+ handling proteins. Impaired myocyte Ca2+ handling plays a key role in cardiac pathophysiology and is a characteristic of cardiac hypertrophy; therefore we examined the potential pro-hypertrophic cardiotoxicity of these bisphenols. Four to five day exposure to BPAF did not cause hypertrophy in normal hiPSC-CMs, but significantly exacerbated the hypertrophic phenotype in myocytes with existing hypertrophy induced by endothelin-1, characterized by increased cell size and elevated expression of the hypertrophic marker proBNP. This pro-hypertrophic cardiotoxicity was also occurred in cardiac organoids, with BPAF having the strongest toxicity, followed by BPA. Our findings demonstrate that long term exposures to BPA and some of its analogs cause contractile dysfunction and abnormal Ca2+ handling, and have potential pro-hypertrophic cardiotoxicity in human heart cells/tissues, and suggest that some bisphenol chemicals may be a risk factor for cardiac hypertrophy in human hearts.