Bisphenol chemicals in colostrum from Shanghai, China during 2006-2019: Concentration, temporal variation, and potential influence on birth parameters.

Bisphenol A (BPA) and its alternatives bisphenol S (BPS) and bisphenol F (BPF) are identified as endocrine disruptors that have negative impacts on infant growth. Their temporal variations in human milk and potential effects on fetal growth are not well known. In this study, colostrum collecting at four time points between 2006 and 2019 and paired urine in 2019 from Shanghai, China, were analyzed for eight bisphenols. The total concentrations in colostrum in 2019 were up to 3.43 ng/mL, with BPA being dominant, followed by BPS and BPF. BPA levels in colostrum noticeably decreased from 2010 to 2013. Additionally, obvious percentage changes in bisphenols were observed in 2019. The BPA concentrations in paired colostrum and urine were not significantly correlated. High levels of BPA in colostrum were linked to a significant reduction in birth head circumference in 2019 (p = 0.031). BPA and BPS in colostrum might have similar negative effect on fetal growth in 2019, but these effects were generally non-significant. Further studies are needed to testify the potential impact. The hazard indexes for infants in the first week of life were below 1, suggesting no obvious health risks. However, the high contribution from BPA still warrants further attention.

Exploring aryl hydrocarbon receptor (AhR) as a target for Bisphenol-A (BPA)-induced pancreatic islet toxicity and impaired glucose homeostasis: Protective efficacy of ethanol extract of Centella asiatica.

The estrogenic impact of Bisphenol-A (BPA), a widely recognized endocrine disruptor, causes disruption of pancreatic ß-cell function through estrogen receptors (ERs). While BPA's binding affinity for ERs is significantly lower than that of its natural counterpart, estrogen, recent observations of BPA's affinity for aryl hydrocarbon receptor (AhR) in specific cellular contexts have sparked a specific question: does AhR play a role in BPA's toxicological effects within the endocrine pancreas? To explore this question, we investigated BPA's (10 and 100 µg/ kg body weight/day for 21 days) potential to activate AhR within pancreatic islets and assessed the protective role of ethanol extract of Centella asiatica (CA) (200 and 400 mg/kg body weight/day for 21 days) against BPA-mediated toxicity in mouse model. Our results indicate that BPA effectively triggers the activation of AhR and modulates its target genes within pancreatic islets. In contrast, CA activates AhR but directs downstream pathways differentially and activates Nrf2. Additionally, CA was observed to counteract the disruption caused by BPA in glucose homeostasis and insulin sensitivity. Furthermore, BPA-induced oxidative stress and exaggerated production of proinflammatory cytokines were effectively counteracted by CA supplementation. In summary, our study suggests that CA influenced AhR signaling to mitigate the disrupted pancreatic endocrine function in BPA exposed mice. By shedding light on how BPA interacts with AhR, our research provides valuable insights into the mechanisms involved in the diabetogenic actions of BPA.

Effects of bisphenol F, bisphenol S, and bisphenol AF on cultured human osteoblasts.

Bisphenol A (BPA) analogs, like BPA, could have adverse effects on human health including bone health. The aim was to determine the effect of BPF, BPS and BPAF on the growth and differentiation of cultured human osteoblasts. Osteoblasts primary culture from bone chips harvested during routine dental work and treated with BPF, BPS, or BPAF for 24 h at doses of 10-5, 10-6, and 10-7 M. Next, cell proliferation was studied, apoptosis induction, and alkaline phosphatase (ALP) activity. In addition, mineralization was evaluated at 7, 14, and 21 days of cell culture in an osteogenic medium supplemented with BP analog at the studied doses. BPS treatment inhibited proliferation in a dose-dependent manner at all three doses by inducing apoptosis; BPF exerted a significant inhibitory effect on cell proliferation at the highest dose alone by an increase of apoptosis; while BPAF had no effect on proliferation or cell viability. Cell differentiation was adversely affected by treatment with BPA analogs in a dose-dependent, observing a reduction in calcium nodule formation at 21 days. According to the results obtained, these BPA analogs could potentially pose a threat to bone health, depending on their concentration in the organism.

Bisphenol A aggravate selenium deficiency-induced apoptosis via miR-215-3p/Dio1 to activate ROS/PI3K/AKT pathway in chicken arterial.

Both bisphenol A (BPA) and selenium (Se) deficiency can affect the expression of microRNAs (miRNAs), which can specifically regulate its target mRNA and induce apoptosis, and play a significant role in cardiovascular injury diseases. To explore the mechanism of apoptosis induced by BPA and Se deficiency in chicken arterial endothelial tissue and the role of miRNAs in this process, the model of BPA exposure/Se deficiency in chicken and PAEC cells have been employed. The targeting relationship between miR-215-3p and iodothyronine deiodinase 1 (Dio1) in PAEC was verified by double luciferase gene report. The level of miR-215-3p was detected by qRT-PCR. The oxidative stress level of arterial endothelial cells was detected by oxidative stress kit and DCFH-DA probe method. The PI3K/AKT pathway, mitochondrial dynamics, and apoptosis-related genes were detected by qRT-PCR and western blot. The mitochondrial ATP level and nitric oxide synthases (NOSs) level were detected with the kit. TUNEL, acridine orange/ethidium bromide, and flow cytometry were used to detect the level of apoptosis. The results showed that BPA exposure and Se deficiency led to overexpression of miR-215-3p, aggravated oxidative stress, inhibited activation of PI3K/AKT pathway, promoted mitochondrial division, increased expression of apoptosis related genes, and finally led to apoptosis of chicken arterial endothelial cells. We also established knockdown/overexpression models of miR-215-3p and Dio1 in vitro, and found that overexpression of miR-215-3p and knockout of Dio1 can induce apoptosis. Interestingly, miR-215-3p-Inhibitor and N-acetyl- l-cysteine (NAC) partially prevented apoptosis caused by BPA exposure and Se deficiency, and LY294002 aggravated apoptosis. These results suggest that BPA exposure aggravates the apoptosis of Se deficient arterial endothelial cells in chickens by regulating the ROS/PI3K/AKT pathway activated by miR-215-3p/Dio1. The miR-215-3p/Dio1 axis provides a new way to understand the toxic mechanism of BPA exposure and Se deficiency, and reveals a new regulatory model of apoptosis damage in vascular diseases.

Effects of Astragalus polysaccharide to boar sperm on bisphenol A exposure.

Bisphenol A (BPA) is reported to impair male fertility. The alleviating effect of Astragalus polysaccharide (APS) on sperm oxidative damage caused by BPA exposure was analysed for the first time. In this study, the effect of APS (0.25, 0.5, 0.75, 1 mg/mL) on motility of BPA-exposed sperm, energy metabolism indexes, and antioxidant parameters was evaluated. In addition, the effects of APS supplementation on protein tyrosine phosphorylation of BPA-exposed sperm were assessed. The results showed that the addition of APS (0.5 and 0.75 mg/mL) significantly increased motility of BPA-exposed sperm by decreasing the content of malondialdehyde and improving activities of superoxide dismutase and catalase (p < .05). Administration of different doses of APS to BPA-exposed sperm improved mitochondrial membrane potential and energy production (p < .05). Moreover, APS protected and alleviated tyrosine phosphorylation protein on the principal-pieces of BPA-exposed sperm flagella. In conclusion, supplementation with APS enhanced the antioxidant capacity of BPA-exposed sperm and improved in vitro capacitation, thereby improving the reproductive capacity of sperm exposed to environmental hormones.

Negative effects of endocrine disruptor bisphenol A on ovarian granulosa cells and the protective role of folic acid.

In brief: Bisphenol A (BPA) is a widely produced chemical, mostly used in the production of polycarbonate plastics, and can act as an endocrine disruptor. This paper focuses on the different effects of BPA on ovarian granulosa cells. Abstract: Bisphenol A (BPA) is an endocrine disruptor (ED), widely used as a comonomer or an additive in the plastics industry. It can be found in food and beverage plastic packaging, epoxy resins, thermal paper and other common products. To date, there have only been several experimental studies to have examined how BPA exposure affects human and mammalian follicular granulosa cells (GCs) in vitro and in vivo; the collected evidence data show that BPA negatively affects the GCs by altering steroidogenesis and gene expression, inducing autophagy, apoptosis and cellular oxidative stress through reactive oxygen species production. Exposure to BPA can also lead to abnormally constrained or elevated cellular proliferation and can even reduce cell viability. Therefore, research on EDs such as BPA is important as it provides some important insights into the causes and development of infertility, ovarian cancer and other conditions related to impaired ovarian and GC function. Folic acid, a biologic form of vitamin B9, is a methyl donor that can neutralize the toxic effects of the BPA exposure and is, as a common food supplement, an interesting option for researching its protective role against ubiquitous harmful EDs such as BPA.

BPA and its alternatives BPF and BPAF exaggerate hepatic lipid metabolism disorders in male mice fed a high fat diet.

Alternatives to Bisphenol A (BPA), such as BPF and BPAF, have found increasing industrial applications. However, toxicological research on these BPA analogues remains limited. This study aimed to investigate the effects of BPA, BPF, and BPAF exposure on hepatotoxicity in mice fed with high-fat diets (HFD). Male mice were exposed to the bisphenols at a dose of 0.05 mg per kg body weight per day (mg/kg bw/day) for eight consecutive weeks, or 5 mg/kg bw/day for the first week followed by 0.05 mg/kg bw/day for seven weeks under HFD. The low dose (0.05 mg/kg bw/day) was corresponding to the tolerable daily intake (TDI) of BPA and the high dose (5 mg/kg bw/day) was corresponding to its no observed adverse effect level (NOAEL). Biochemical analysis revealed that exposure to these bisphenols resulted in liver damage. Metabolomics analysis showed disturbances of fatty acid and lipid metabolism in bisphenol-exposed mouse livers. BPF and BPAF exposure reduced lipid accumulation in HFD mouse liver by lowering glyceride and cholesterol levels. Transcriptomics analysis demonstrated that expression levels of genes related to fatty acid synthesis and metabolism were changed, which might be related to the activation of the PPAR signaling pathway. Besides, a feedback regulation mechanism might exist to maintain hepatic metabolic homeostasis. For the first time, this study demonstrated the effects of BPF and BPAF exposure in HFD-mouse liver. Considering the reality of the high prevalence of obesity nowadays and the ubiquitous environmental distribution of bisphenols, this study provides insight and highlights the adverse effects of BPA alternatives, further contributing to the consideration of the safe use of such compounds.

Foetal exposure to the bisphenols BADGE and BPAF impairs meiosis through DNA oxidation in mouse ovaries.

Many endocrine disruptors have been proven to impair the meiotic process which is required for the production of healthy gametes. Bisphenol A is emblematic of such disruptors, as it impairs meiotic prophase I and causes oocyte aneuploidy following in utero exposure. However, the mechanisms underlying these deleterious effects remain poorly understood. Furthermore, the increasing use of BPA alternatives raises concerns for public health. Here, we investigated the effects of foetal exposure to two BPA alternatives, bisphenol A Diglycidyl Ether (BADGE) and bisphenol AF (BPAF), on oogenesis in mice. These compounds delay meiosis initiation, increase the number of MLH1 foci per cell and induce oocyte aneuploidy. We further demonstrate that these defects are accompanied by changes in gene expression in foetal premeiotic germ cells and aberrant mRNA splicing of meiotic genes. We observed an increase in DNA oxidation after exposure to BPA alternatives. Specific induction of oxidative DNA damage during foetal germ cell differentiation causes similar defects during oogenesis, as observed in 8-oxoguanine DNA Glycosylase (OGG1)-deficient mice or after in utero exposure to potassium bromate (KBrO3), an inducer of oxidative DNA damage. The supplementation of BPA alternatives with N-acetylcysteine (NAC) counteracts the effects of bisphenols on meiosis. Together, our results propose oxidative DNA lesion as an event that negatively impacts female meiosis with major consequences on oocyte quality. This could be a common mechanism of action for numerous environmental pro-oxidant pollutants, and its discovery, could lead to reconsider the adverse effect of bisphenol mixtures that are simultaneously present in our environment.

Gestational bisphenol A exposure advances puberty onset in female offspring: Critical time window identification.

Increasing evidence shows that the early onset of puberty in female offspring may be caused by maternal prenatal exposure to bisphenol A (BPA) during pregnancy; however, the critical time window of maternal prenatal BPA exposure remains unknown. Here, we identify the critical time window of gestational BPA exposure that induces early onset of puberty in female offspring. Pregnant CD-1 mice were gavaged with BPA (8 mg/kg) daily during the early gestational stage (GD1-GD6), middle gestational stage (GD7-GD12) or late gestational stage (GD13-GD18). We show that maternal BPA exposure during the early and middle gestational stages could advance the vaginal opening time and increase the serum levels of kisspeptin-10 and GnRH in the female offspring at PND 34. Mechanistically, maternal BPA exposure during early and middle gestation could significantly increase CpG island methylation in the Eed gene promoters but reduce the mRNA expression of Eed in the hypothalamus tissues of the female offspring. In conclusion, the critical period of maternal BPA exposure-induced early onset of puberty in female offspring is early and middle gestation; this BPA-induced early onset of puberty might be partly attributed to epigenetic programming of the Eed gene in the hypothalamus. This study provides important insights regarding the relationship and the mechanisms between BPA and offspring pubertal development.

Ameliorative effect of vitamin E and selenium against bisphenol A-induced toxicity in spinal cord and submandibular salivary glands of adult male albino rats.

Bisphenol A (BPA) used in plastic industry. This study evaluate ameliorative effect of vitamin E and selenium in combating BPA toxicity in spinal cord (SC) and submandibular glands (SMGs). Thirty rats divided into three groups [Group I, controls; Group II, BPA orally (25 mg/kg) three times a week, 60 days; Group III, BPA (25 mg/kg) plus vitamin E and selenium in water (1 ml/L/day)]. By histopathological, immunohistochemical, and biochemical investigations. Bisphenol A group showed degenerative alterations. SC gray matter showed pyknotic nuclei and white matter revealed neuropil degeneration. Myelinated fibers showed dispersed myelin. SMGs, exhibited vacuolated cytoplasm in acinar cells. Intense glial fibrillary acidic protein in SC and strong proliferating cell nuclear antigen in acinar and ductal cell nuclei of SMGs. Malondialdehyde elevated in SC and catalase decreased in SMG. Group III, SC and SMG revealed partial recovery. Vitamin E and selenium displayed protective effects against BPA toxicity in SC and SMGs.

BPA had a neurotoxic effect on spinal cord of albino rats.BPA causing degeneration of nerve fibers with axonal disappearance of white matter.BPA caused GFAP proliferation and high MDA level in spinal cord.BPA caused degeneration of submandibular gland's acinar cells and duct system.Both vitamin E and Selenium had a protective effect against BPA toxicity.

Effect of bromelain on sperm quality, testicular oxidative stress and expression of oestrogen receptors in bisphenol-A treated male mice.

Bisphenol A (BPA) as an endocrine-disrupting chemical (EDC) with low estrogenic activity increases oxidative stress and testicular damage. Bromelain is a mixture of different thiol endopeptidases and other components with many uses as a natural anti-inflammatory enzyme. The present study aimed to evaluate the effect of bromelain on male reproductive failure induced by BPA. A total of 60 healthy adult male mice were randomly divided into six groups (n = 6), including control, bromelain (70 mg/kg), BPA (5 and 600 mg/kg), and BPA (5 and 600 mg/kg) + bromelain. BPA and bromelain were administrated orally for 35 days. Then, the epididymis and testes were removed to evaluate sperm parameters, oxidative stress markers, serum levels of testosterone concentrations, and oestrogen receptors expression. The BPA significantly (P < 0.05) decreased sperm count, motility, viability, and normal sperm morphology, as well as testosterone levels, oestrogen receptors alpha (ERα) and beta (ERß), GPx, CAT, and SOD activity than control. Also, BPA significantly (P < 0.05) increased the sperm anomalies, and MDA concentration. Co-administration of bromelain + BPA caused a significantly (P < 0.05) increase sperm count, normal sperm morphology, testosterone levels, expression of ERα and ERß, and GPx, CAT, and SOD activity than the BPA group (P < 0.05). Also, Bromelain significantly (P < 0.05) decreased sperm anomalies and MDA concentration than control. Based on the results of this study, it appears that BPA causes side effects on male reproduction. While, bromelain has the potential to reduce the side effects of BPA on the male reproductive system.

Neuroprotective effect of Biochanin a against Bisphenol A-induced prenatal neurotoxicity in zebrafish by modulating oxidative stress and locomotory defects.

Exogenous toxicants cause oxidative stress and damage to brain cells, resulting in inflammation. Neuroinflammation is important in the pathobiology of various neurological illnesses, including Alzheimer's disease (AD). In this context, Bisphenol A (BPA), a common toxin, causes oxidative damage and has been linked to neurological problems. An O-methylated isoflavone known as Biochanin A (5,7-dihydroxy-4'-methoxy-isoflavone, BCA) is considered to be a phytoestrogen, which is abundant in some legume plants and soy which have preventive effects against cancer, osteoporosis, menopausal symptoms and oxidative stress. However, the mechanism by which BCA protected the prenatal neurological stress are not known. So that, in this study we investigated the BCA neuroprotective effect against BPA-induced neuroinflammation in zebrafish embryo models. For this study, fertilized zebrafish embryos are exposed to BPA (1 µM) with or without BCA. Our finding suggested that BCA co-exposure prevented the depletion of antioxidant defense enzymes by BPA and reduced the production of intracellular ROS production, superoxide anion (O2-), lipid peroxidation (LPO), lactate dehydrogenase (LDH) and nitric oxide (NO) levels in the head that aided in safeguarding neuronal development. Baseline locomotion was rendered and a total distance was calculated to assess the motor function. Exposure to BCA increased acetylcholinestrase (AChE) and improved motor neuron functions. It also reduced the pro-inflammatory response expression and prevented neuroinflammation. Our study suggests that BCA has a positive role in the attenuation or amelioration of neuronal oxidative damage and locomotory behaviour induced by BPA.

Bisphenol A aggravates renal apoptosis and necroptosis in selenium-deficient chickens via oxidative stress and PI3K/AKT pathway.

Bisphenol A (BPA) in the environment can have deleterious effects on humans and animals. BPA can exert nephrotoxicity by inducing oxidative stress. Selenium (Se) deficiency can specifically impair kidney tissues and additionally show a synergistic effect on the toxicity of several environmental chemicals. However, the toxic effects of BPA on the chicken kidney and whether Se deficiency produces synergistic effects on the toxicity of BPA remain poorly understood. Herein, we established BPA exposure models and Se deficiency model in vivo and in vitro, and described the discovery path of BPA aggravation on apoptosis and necroptosis in Se-deficient chicken kidneys via regulation of oxidative stress and phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. We found that BPA exposure increased reactive oxygen species and malondialdehyde levels, reduced activities of catalase, GPx, and superoxide dismutase, downregulated PI3K and AKT expressions, activated Bcl/Bax-Caspase 9-Caspase 3, and receptor-interacting protein kinase 1/mixed lineage kinase domain-like protein signaling pathways, resulting in apoptosis and necroptosis in the chicken kidney. In addition, Se deficiency significantly promoted the expression of renal apoptosis and necroptosis in BPA-exposed chicken kidneys. Altogether, our results showed that BPA aggravates apoptosis and necroptosis in Se-deficient chicken kidneys via regulation of oxidative stress and PI3K/AKT signaling pathway. Our findings elucidate the mechanism of BPA nephrotoxicity and Se deficiency exacerbation toxicity in chickens and will provide great significance for the protection of the ecological environment and animal health.

Silibinin and Naringenin against Bisphenol A-Induced Neurotoxicity in Zebrafish Model-Potential Flavonoid Molecules for New Drug Design, Development, and Therapy for Neurological Disorders.

Bisphenol A (BPA), a well-known xenoestrogen, is commonly utilised in the production of polycarbonate plastics. Based on the existing evidence, BPA is known to induce neurotoxicity and behavioural issues. Flavonoids such as silibinin and naringenin have been shown to have biological activity against a variety of illnesses. The current research evaluates the neuropharmacological effects of silibinin and naringenin in a zebrafish model against neurotoxicity and oxidative stress caused by Bisphenol A. In this study, a novel tank diving test (NTDT) and light−dark preference test (LDPT) were used in neurobehavioural investigations. The experimental protocol was planned to last 21 days. The neuroprotective effects of silibinin (10 µM) and naringenin (10 µM) in zebrafish (Danio rerio) induced by BPA (17.52 µM) were investigated. In the brine shrimp lethality assay, the 50% fatal concentrations (LC50) were 34.10 µg/mL (silibinin) and 91.33 µg/mL (naringenin) compared to the standard potassium dichromate (13.15 µg/mL). The acute toxicity investigation found no mortality or visible abnormalities in the silibinin- and naringenin-treated groups (LC50 > 100 mg/L). The altered scototaxis behaviour in LDPT caused by BPA was reversed by co-supplementation with silibinin and naringenin, as shown by decreases in the number of transitions to the light zone and the duration spent in the light zone. Our findings point to BPA's neurotoxic potential in causing altered scototaxis and bottom-dwelling behaviour in zebrafish, as well as the usage of silibinin and naringenin as potential neuroprotectants.

Exposure to low-dose bisphenol A induces spleen damage in a murine model: Potentially through oxidative stress?

Background: During early life, exposure to environmental toxicants, including endocrine disruptor bisphenol A (BPA), can be detrimental to the immune system. To our knowledge, a few researches have looked at the effects of developing BPA exposures on the spleen. Aim: The murine model was developed to investigate the underlying molecular mechanisms and mode of BPA actions on the spleen subsequent to prolonged early-life exposure to BPA. Methods: Immature (3-week-old) male and female Swiss Albino mice were intraperitoneally injected with 50 µg/kg BPA in corn oil or corn oil alone for 6 weeks. Mouse spleens were harvested and examined histologically at 10 weeks old (adulthood). Results: We observed neurobehavioral impairments and a significant increase in peripheral monocyte and lymphocyte counts in mice (males and females). Moreover, several spleen abnormalities in both male and female mice were observed in adulthood. BPA-treated mice's histopathological results revealed toxicity in the form of significantly active germinal centers of the white pulp and a few apoptotic cells. There was also a notable invasion of the red pulp by eosinophils and lymphocytes that were significantly higher than normal. Agarose gel electrophoresis provided further evidence of internucleosomal DNA fragmentation and apoptosis in the splenic tissues of BPA-treated mice compared to controls. In addition, there were increased levels of the lipid peroxidation malondialdehyde end-product, a marker of oxidative lipid damage, in the spleens of BPA-treated mice compared to controls. Conclusion: Our study provides evidence that oxidative stress injury induced by early-life exposures to BPA could contribute to a range of splenic tissue damages during adulthood.

Protective effect of the association of curcumin with piperine on prostatic lesions: New perspectives on BPA-induced carcinogenesis.

Bisphenol A (BPA) is a chemical agent which can exert detrimental effects on the male reproductive system, especially the prostate gland. In this study we described the efficacy of the dietary agent curcumin, alone or combined with piperine, to suppress the impact of BPA on the prostate. Adult gerbils were divided into nine experimental groups (n = 7 each group), regarding control (water and oil), exposed to BPA (50 µg/kg/day in water) or curcumin (100 mg/kg) and/or piperine (20 mg/kg). To evaluate the effects of the phytotherapic agents, the other groups received oral doses every two days, BPA plus curcumin (BCm), piperine (BP), and curcumin + piperine (BCmP). BPA promoted prostatic inflammation and morphological lesions in ventral and dorsolateral prostate lobes, associated with an increase in androgen receptor-positive cells and nuclear atypia, mainly in the ventral lobe. Curcumin and piperine helped to minimize these effects. BPA plus piperine or curcumin showed a reduction in nuclear atypical phenotype, indicating a beneficial effect of phytochemicals. Thus, these phytochemicals minimize the deleterious action of BPA in prostatic lobes, especially when administered in association. The protective action of curcumin and piperine consumption is associated with weight loss, anti-inflammatory potential, and control of prostate epithelial cell homeostasis.

Suppression of bisphenol A-induced oxidative stress by taurine promotes neuroprotection and restores altered neurobehavioral response in zebrafish (Danio rerio).

Bisphenol A (BPA) has been documented as a mediator for a number of health effects, including inflammation, oxidative stress, carcinogenicity, and mood dysfunction. The literature on the role of BPA in inducing altered neurobehavioral response and brain morphology and plausible neuroprotective role of taurine against BPA induced oxidative stress mediated neurotoxicity is limited. Therefore, the present experimental paradigm was set for 21 days to expound the neuroprotective efficacy of taurine against BPA-induced neurotoxicity in zebrafish (Danio rerio) following waterborne exposure. Neurobehavioral studies were conducted by light-dark preference test (LDPT) and novel tank diving test (NTDT). To validate that the neuroprotective efficacy of taurine against BPA-induced neurotoxicity is associated with the modulation of the antioxidant defense system, we have conducted biochemical studies in zebrafish brain. Changes in brain morphology leading to neurobehavioral variations following co-supplementation of BPA and taurine were evaluated by Hoechst staining and cresyl violet staining (CVS) in periventricular gray zone (PGZ) of zebrafish brain. Our findings show that taurine co-supplementation significantly improved the BPA-induced altered scototaxis and explorative behavior of zebrafish. Further, BPA-induced augmented oxidative stress was considerably ameliorated by taurine co-supplementation. Subsequently, our observation also points toward the neuroprotective role of taurine against BPA-induced neuronal pyknosis and chromatin condensation in PGZ of zebrafish brain. In a nutshell, the findings of the current study show the neuroprotective efficacy of taurine against BPA-induced oxidative stress-mediated neurotoxicity. Elucidation of the underlying signaling mechanism of taurine-mediated neuroprotection would provide novel strategies for the prevention/treatment of BPA-persuaded serious neurological consequences.

Resveratrol Butyrate Esters Inhibit Obesity Caused by Perinatal Exposure to Bisphenol A in Female Offspring Rats.

Resveratrol butyrate esters (RBE) are derivatives of resveratrol (RSV) and butyric acid and exhibit biological activity similar to that of RSV but with higher bioavailability. The aim of this study was designed as an animal experiment to explore the effects of RBE on the serum biochemistry, and fat deposits in the offspring rats exposed to bisphenol A (BPA), along with the growth and decline of gut microbiota. We constructed an animal model of perinatal Bisphenol A (BPA) exposure to observe the effects of RBE supplementation on obesity, blood lipids, and intestinal microbiota in female offspring rats. Perinatal exposure to BPA led to weight gain, lipid accumulation, high levels of blood lipids, and deterioration of intestinal microbiota in female offspring rats. RBE supplementation reduced the weight gain and lipid accumulation caused by BPA, optimised the levels of blood lipids, significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio, and increased and decreased the abundance of S24-7 and Lactobacillus, respectively. The analysis of faecal short-chain fatty acid (SCFA) levels revealed that BPA exposure increased the faecal concentration of acetate, which could be reduced via RBE supplementation. However, the faecal concentrations of propionate and butyrate were not only significantly lower than that of acetate, but also did not significantly change in response to BPA exposure or RBE supplementation. Hence, RBE can suppress BPA-induced obesity in female offspring rats, and it demonstrates excellent modulatory activity on intestinal microbiota, with potential applications in perinatological research.

Bisphenol S and Bisphenol F Are Less Disruptive to Cardiac Electrophysiology, as Compared With Bisphenol A.

Bisphenol A (BPA) is a high-production volume chemical used to manufacture consumer and medical-grade plastic products. Due to its ubiquity, the general population can incur daily environmental exposure to BPA, whereas heightened exposure has been reported in intensive care patients and industrial workers. Due to health concerns, structural analogs are being explored as replacements for BPA. This study aimed to examine the direct effects of BPA on cardiac electrophysiology compared with recently developed alternatives, including BPS (bisphenol S) and BPF (bisphenol F). Whole-cell voltage-clamp recordings were performed on cell lines transfected to express the voltage-gated sodium channel (Nav1.5), L-type voltage-gated calcium channel (Cav1.2), or the rapidly activating delayed rectifier potassium channel (hERG). Cardiac electrophysiology parameters were measured using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and intact, whole rat heart preparations. BPA was the most potent inhibitor of fast/peak (INa-P) and late (INa-L) sodium channel (IC50 = 55.3, 23.6 µM, respectively), L-type calcium channel (IC50 = 30.8 µM), and hERG channel current (IC50 = 127 µM). Inhibitory effects on L-type calcium channels were supported by microelectrode array recordings, which revealed a shortening of the extracellular field potential (akin to QT interval). BPA and BPF exposures slowed atrioventricular (AV) conduction and increased AV node refractoriness in isolated rat heart preparations, in a dose-dependent manner (BPA: +9.2% 0.001 µM, +95.7% 100 µM; BPF: +20.7% 100 µM). BPS did not alter any of the cardiac electrophysiology parameters tested. Results of this study demonstrate that BPA and BPF exert an immediate inhibitory effect on cardiac ion channels, whereas BPS is markedly less potent. Additional studies are necessary to fully elucidate the safety profile of bisphenol analogs on the heart.

Variably methylated retrotransposons are refractory to a range of environmental perturbations.

The agouti viable yellow (Avy) allele is an insertional mutation in the mouse genome caused by a variably methylated intracisternal A particle (VM-IAP) retrotransposon. Avy expressivity is sensitive to a range of early-life chemical exposures and nutritional interventions, suggesting that environmental perturbations can have long-lasting effects on the methylome. However, the extent to which VM-IAP elements are environmentally labile with phenotypic implications is unknown. Using a recently identified repertoire of VM-IAPs, we assessed the epigenetic effects of different environmental contexts. A longitudinal aging analysis indicated that VM-IAPs are stable across the murine lifespan, with only small increases in DNA methylation detected for a subset of loci. No significant effects were observed after maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation. A genetic mouse model of abnormal folate metabolism exhibited shifted VM-IAP methylation levels and altered VM-IAP-associated gene expression, yet these effects are likely largely driven by differential targeting by polymorphic KRAB zinc finger proteins. We conclude that epigenetic variability at retrotransposons is not predictive of environmental susceptibility.