Bisphenol A Treatment Research Articles

BPS-induced ovarian dysfunction: Protective actions of melatonin via modulation of SIRT-1/Nrf2/NFĸB and IR/PI3K/pAkt/GLUT-4 expressions in adult golden hamster.

Ever-increasing occurrence of plastic-manufacturing industries leads to environmental pollution that has been associated with declined human health and increased incidence of compromised reproductive health. Female subfertility/infertility is a complex phenomenon and environmental toxicants as well as lifestyle factors have a crucial role to play. Bisphenol S (BPS) was believed to be a "safer" replacement of bisphenol A (BPA) but recent data documented its neurotoxic, hepatotoxic, nephrotoxic, and reprotoxic attributes. Hence based on the scarcity of reports, we investigated molecular insights into BPS-induced ovarian dysfunction and protective actions of melatonin against it in adult golden hamsters, Mesocricetus auratus. Hamsters were administered with melatonin (3 mg/kg BW i.p. alternate days) and BPS (150 mg/kg BW orally every day) for 28 days. BPS treatment disrupted hypothalamo-pituitary-ovarian (HPO) axis as evident by reduced gonadotropins such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH), ovarian steroids such as estradiol (E2) and progesterone (P4), thyroid hormones namely triiodothyronine (T3) and thyroxine (T4) and melatonin levels along with their respective receptors (ERα, TRα, and MT-1) thereby reducing ovarian folliculogenesis. BPS exposure also led to ovarian oxidative stress/inflammation by increasing reactive oxygen species and metabolic disturbances. However, melatonin supplementation to BPS restored ovarian folliculogenesis/steroidogenesis as indicated by increased number of growing follicles/corpora lutea and E2/P4 levels. Further, melatonin also stimulated key redox/survival markers such as silent information regulator of transcript-1 (SIRT-1), forkhead box O-1 (FOXO-1), nuclear factor E2-related factor-2 (Nrf2), and phosphoinositide 3-kinase/protein kinase B (PI3K/pAkt) expressions along with enhanced ovarian antioxidant capacity. Moreover, melatonin treatment reduced inflammatory load including ovarian nuclear factor kappa-B (NFĸB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expressions, serum tumor necrosis factor α (TNFα), C-reactive protein (CRP) and nitrite-nitrate levels as well as upregulated ovarian insulin receptor (IR), glucose uptake transporter-4 (GLUT-4), connexin-43, and proliferating cell nuclear antigen (PCNA) expressions in ovary thereby ameliorating inflammatory and metabolic alterations due to BPS. In conclusion, we found severe deleterious impact of BPS on ovary while melatonin treatment protected ovarian physiology from these detrimental changes suggesting it to be a potential preemptive candidate against environmental toxicant-compromised female reproductive health.

ROS mediated pyroptosis-M1 polarization crosstalk participates in inflammation of chicken liver induced by bisphenol A and selenium deficiency

The earth's natural environmental factors and man-made industrial pollution often lead to the co-occurrence of environmental pathogenic factors and malnutrition. Bisphenol A (BPA) is a serious environmental endocrine disruptor, and its exposure can cause liver tissue damage. Selenium (Se) deficiency is a worldwide problem that afflicts thousands of people, and Se deficiency can cause M1/M2 imbalance. In addition, the crosstalk between hepatocyte and immune cell is closely related to the occurrence of hepatitis. Therefore, this study found for the first time that the combined exposure of BPA and Se deficiency caused liver pyroptosis and M1 polarization through ROS, and the crosstalk between pyroptosis and M1 polarization aggravated liver inflammation in chicken. In this study, the BPA or/and Se deficiency chicken liver, single and co-culture model of LMH and HD11 cells were established. The results displayed that BPA or Se deficiency induced liver inflammation accompanied by pyroptosis and M1 polarization through oxidative stress, and increased expressions of chemokines (CCL4, CCL17, CCL19, and MIF) and inflammatory factors (IL-1β and TNF-α). The vitro experiments further verified the above changes and showed that LMH pyroptosis promoted M1 polarization of HD11 cells, and vice versa. NAC counteracted pyroptosis and M1 polarization caused by BPA and low-Se, reducing the release of inflammatory factors. In brief, BPA and Se deficiency treatment can exacerbate liver inflammation by increasing oxidative stress to induce pyroptosis and M1 polarization.

Stage-Related Neurotoxicity of BPA in the Development of Zebrafish Embryos

Bisphenol A (BPA) is one of the most widely produced chemicals in the world used in the production of epoxy resins and polycarbonate plastics. BPA is easily migrated from the outer packaging to the contents. Due to the lipophilic property, BPA is easily accumulated in organisms. Perinatal low-dose BPA exposure alters brain neural development in later generations. In this study, after BPA treatment, the spontaneous movement of zebrafish larvae from the cleavage period to the segmentation period (1-24 hpf) was significantly decreased, with speed decreasing by 18.97% and distance decreasing between 18.4 and 29.7% compared to controls. Transcriptomics analysis showed that 131 genes were significantly differentially expressed in the exposed group during the 1-24 hpf period, among which 39 genes were significantly upregulated and 92 genes were significantly downregulated. The GO enrichment analysis, gene function analysis and real-time quantitative PCR of differentially expressed genes showed that the mRNA level of guanine deaminase (cypin) decreased significantly in the 1-24 hpf period. Moreover, during the 1-24 hpf period, BPA exposure reduced guanine deaminase activity. Therefore, we confirmed that cypin is a key sensitive gene for BPA during this period. Finally, the cypin mRNA microinjection verified that the cypin level of zebrafish larvae was restored, leading to the restoration of the locomotor activity. Taken together, the current results show that the sensitive period of BPA to zebrafish embryos is from the cleavage period to the segmentation period (1-24 hpf), and cypin is a potential target for BPA-induced neurodevelopmental toxicity. This study provides a potential sensitive period and a potential target for the deep understanding of neurodevelopmental toxicity mechanisms caused by BPA.

Impacts of bisphenol A on growth and reproductive traits of submerged macrophyte Vallisneria natans.

Bisphenol A (BPA) is considered a contaminant of emerging concern and interferes with the normal activities of living organisms. The toxicity of BPA is evident in animals and terrestrial plants. However, the response of aquatic plants to low BPA concentrations is still unclear. In the present study, effects of varying BPA loadings (targeting at 0.01, 0.1, and 1mg/L) on the growth and reproductive traits of the dioecious annual submerged macrophyte Vallisneria natans were assessed through a 5-month experiment. The results showed that BPA inhibited the elongation of V. natans leaves but resulted in an increase in leaf number and ramet number under the highest BPA loading treatment (targeting at 1mg/L). In addition, detectable biochemical changes in the total carbon and soluble sugar contents were found, which both were significantly higher at the highest BPA loading treatment. However, the total biomass did not alter significantly after the BPA treatments, indicating that BPA did not induce direct toxic effects on the growth of V. natans. At the highest BPA loading treatment, female individuals of V. natans allocated less number for ramet than male ones, showing a clear sexual dimorphism. No significant differences between the five treatments were found for the flower or fruit traits, while the germination rate was significantly inhibited for the seeds collected from the highest BPA loading treatment. In conclusion, V. natans tolerated low concentrations of BPA by making a trade-off between ramet (leaf) number and leaf elongation, as well as modulating the total carbon and soluble sugar contents. However, serious consequence of decline in seed viability implied that the impact of BPA on plant reproduction were usually underestimated.

Sulforaphane ameliorates bisphenol A-induced hepatic lipid accumulation by inhibiting endoplasmic reticulum stress

The aim of the present study was to investigate the role of endoplasmic reticulum (ER) stress in bisphenol A (BPA) – induced hepatic lipid accumulation as well as the protective effects of Sulforaphane (SFN) in this process. Human hepatocyte cell line (LO2) and C57/BL6J mice were used to examine BPA-triggered hepatic lipid accumulation and the underlying mechanism. Hepatic lipid accumulation, triglycerides (TGs) levels, the expression levels of lipogenesis-related genes and proteins in the ER stress pathway were measured. It was revealed that BPA treatment increased the number of lipid droplets, the levels of TG and mRNAs expression of lipogenesis-related genes, and activated the ER stress pathway. These changes were inhibited by an ER stress inhibitor 4-phenylbutyric acid. SFN treatment abrogated BPA-altered hepatic lipid metabolism and ameliorated BPA-induced ER stress-related markers. Together, these findings suggested that BPA activated ER stress to promote hepatic lipid accumulation, and that SFN reversed those BPA effects by alleviating ER stress.

Modulation of Unfolded Protein Response Restores Survival and Function of β-Cells Exposed to the Endocrine Disruptor Bisphenol A.

Diabetes is a metabolic disease that currently affects nearly half a billion people worldwide. β-cells dysfunction is one of the main causes of diabetes. Exposure to endocrine-disrupting chemicals is correlated with increased diabetes incidence. We hypothesized that treatment with bisphenol A (BPA) induces endoplasmic reticulum (ER) stress that activates the unfolded protein response (UPR), leading to impaired function of the β-cells, which over time, can cause diabetes. In this study, we aimed to evaluate UPR pathways activation under BPA treatment in β-cells and possible recovery of ER homeostasis. MIN6 cells (mouse insulinoma cell line) and isolated pancreatic islets from NOR (non-obese diabetes resistant) mice were treated with BPA. We analyzed the impact of BPA on β-cell viability, the architecture of the early secretory pathway, the synthesis and processing of insulin and the activation of UPR sensors and effectors. We found that the addition of the chemical chaperone TUDCA rescues the deleterious effects of BPA, resulting in improved viability, morphology and function of the β-cells. In conclusion, we propose that modulators of UPR can be used as therapeutic interventions targeted towards regaining β-cells homeostasis.

The antioxidant effects of coenzyme Q10 on albino rat testicular toxicity and apoptosis triggered by bisphenol A.

Polycarbonate plastics for packaging and epoxy resins are both made with the industrial chemical bisphenol A (BPA). This investigation looked at the histological structure, antioxidant enzymes, and albino rats' testis to determine how coenzyme Q10 (CoQ10) impacts BPA toxicity. For the experiments, three sets of 18 male adult rats were created: group 1 received no therapy, group 2 acquired BPA, and group 3 got the daily BPA treatment accompanied by coenzyme Q10, 1h apart. The experimental period ran for 14days. The biochemical biomarkers catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) were altered as a result of BPA exposure. The testicular histological architecture, which is made up of apoptosis, was also exaggerated. Furthermore, rats given BPA and CoQ10 treatment may experience a diminution in these negative BPA effects. These protective properties of CoQ10 may be correlated with the ability to eliminate oxidizing substances that can harm living species. The outcomes might support the hypothesis that CoQ10 prevented oxidative damage and boosted rats' stress responses when BPA was introduced. Thus, by shielding mammals from oxidative stress, CoQ10 aids in the growth and development of the animals. BPA is extremely hazardous to humans and can persist in tissues. Human reproductive functions are a worry due to human exposure to BPA, especially for occupational workers who are typically exposed to higher doses of BPA. As a result, in order to reduce the health risks, BPA usage must be minimized across a diverse range of industries, and improper plastic container handling must be prohibited. By giving CoQ10 to patients, BPA's harmful effects on reproductive structures and functions may be avoided.

Bisphenol S exposure promotes cell apoptosis and mitophagy in murine osteocytes by regulating mtROS signaling.

Bisphenol S (BPS), a safer alternative to bisphenol A, is commonly used as a plasticizer to manufacture various food-packaging materials. The accumulated BPS inhibits osteoblastic bone formation and promotes osteoclastogenesis, thereby accelerating remarkable bone destruction, but it is unclear whether BPS affects osteocytes, comprising over 95% of all bone cells. This study aimed to investigate the biological effect of BPS on osteocytes in vitro, as well as the detailed mechanism. Results showed that BPS (200, 400 μmol/L) exposure caused dose-dependently cell death of osteocytes MLO-Y4, and increased cell apoptosis. BPS induced loss of mitochondrial membrane potential (MMP) and mitochondria impairment. Furthermore, BPS upregulated expressions of mitophagy-related proteins including microtubule-associated protein light chain 3 (LC-3) II and PTEN-induced putative kinase (PINK) 1, accompanied by elevation of autophagy flux and the accumulation of acidic vacuoles; whereas p62 level was downregulated after BPS treatment. Additionally, BPS triggered the production of intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS), while it decreased expression levels of nuclear factor E2-related factor 2 (Nrf2) and quinone oxidoreductase 1 (NQO1). The specific mtROS scavenger MitoTEMPO reversed cell apoptosis and mitophagy, suggesting that mtROS contributes to BPS exposure-induced apoptosis and mitophagy in MLO-Y4 cells. Our data first provide novel evidence that apoptosis and mitophagy as cellular mechanisms for the toxic effect of BPS on osteocytes, thereby helping our understanding of the potential role of osteocytes in the adverse effect of BPS and its analogs on bone growth, and supporting strategies targeting bone destruction caused by BPS.

Bisphenol A exposure inhibits vascular smooth muscle cell responses: Involvement of proliferation, migration, and invasion

Previous studies have associated bisphenol A (BPA) with malignant tumor formation, infertility, and atherosclerosis in vitro and in vivo. However, the precise mechanisms through which BPA affects the cardiovascular system under normal conditions remain unclear. Therefore, this study investigated the biological mechanisms through which BPA affects the responses of aortic vascular smooth muscle cells (VSMCs). BPA treatment inhibited the proliferative activity of VSMCs and induced G2/M-phase cell cycle arrest via stimulation of the ATM-CHK2-Cdc25C-p21WAF1-Cdc2 cascade in VSMCs. Furthermore, BPA treatment upregulated the phosphorylation of mitogen-activated protein kinase (MAPK) pathways such as ERK, JNK, and p38 MAPK in VSMCs. However, the phosphorylation level of AKT was down-regulated by BPA treatment. Additionally, the phosphorylation of ERK, JNK, and p38 MAPK was suppressed when the cells were treated with their respective inhibitors (U0126, SP600125, and SB203580). BPA suppressed MMP-9 activity by reducing the binding activity of AP-1, Sp-1, and NF-κB, thus inhibiting the invasive and migratory ability of VSMCs. These data demonstrate that BPA interferes with the proliferation, migration, and invasion capacities of VSMCs. Therefore, our findings suggest that overexposure to BPA can lead to cardiovascular damage due to dysregulated VSMC responses.

Bisphenol S induces oxidative stress-mediated impairment of testosterone synthesis by inhibiting the Nrf2/HO-1 signaling pathway.

Bisphenol S (BPS) is an environmental endocrine disruptor widely used in industrial production. BPS induces oxidative stress and exhibits male reproductive toxicity in mice, but the mechanisms by which BPS impairs steroid hormone synthesis are not fully understood. Nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 signaling is a key pathway in improving cellular antioxidant defense capacities. Therefore, this study explored the effects of exposure to BPS on testosterone synthesis in adult male mice and its mechanisms with regard to the Nrf2/HO-1 signaling pathway. Adult male C57BL/6 mice were orally exposed to BPS (2, 20, and 200 mg/kg BW) with sesame oil as a vehicle (0.1 ml/10 g BW) per day for 28 consecutive days. The results showed that compared with the control group, serum testosterone levels were substantially reduced in the 20 and 200 mg/kg BPS treatment groups, and testicular testosterone levels were reduced in all BPS treatment groups. These changes were accompanied by a prominent decrease in the expression levels of testosterone synthesis-related enzymes (STAR, CYP11A1, CYP17A1, HSD3B1, and HSD17B3) in the mouse testis. In addition, BPS induced oxidative stress in the testis by upregulating the messenger RNA and protein levels of Keap1 and downregulating the levels of Nrf2, HO-1, and downstream antioxidant enzymes (CAT, SOD1, and Gpx4). In summary, our results indicate that exposure of adult male mice to BPS can inhibit Nrf2/HO-1 signaling and antioxidant enzyme activity, which induces oxidative stress and thereby may impair testosterone synthesis in testicular tissues, leading to reproductive damage.

Mechanism of bisphenol S exposure on color sensitivity of zebrafish larvae

Color vision, initiated from cone cells, is vitally essential for identifying environmental information in vertebrate. Although the retinotoxicity of bisphenol S (BPS) has been reported, data on the influence of BPS treatment on cone cells are scarce. In the present study, transgenic zebrafish (Danio rerio) labeling red and ultraviolet (UV) cones were exposed to BPS (0, 1, 10, and 100 μg/L) during the early stages of retinal development, to elucidate the mechanism underlying its retinal cone toxicity of BPS. The results showed that 10 and 100 μg/L BPS induced oxidative DNA damage, structural damage (decreased number of ribbon synapses), mosaic patterning disorder, and altered expression of genes involved in the phototransduction pathway in red and UV cones. Furthermore, BPS exposure also caused abnormal development of key neurons (retinal ganglion cells, optic nerve, and hypothalamus), responsible for transmitting the light-electrical signal to brain, and thereby resulted in inhibition of light-electrical signal transduction, finally diminishing the spectral sensitivity of zebrafish larvae to long- and short-type light signal at 5 day post fertilization. This study highlights the cone-toxicity of environmental relevant concentrations of BPS, and clarifies the mechanism of color vision impairment induced by BPS at the cellular level, updating the understanding of visual behavior driven by environmental factors.

Promoted BPA degradation in food waste leachate via alkali-fluffed CoFe2O4@CoSiOx activated PMS under the assistance of inherent acetate

The removal of bisphenol A (BPA) from food waste leachate (FWL) is challenging but of great significance. Herein, an alkali post-treatment approach was performed to obtain the fluffed hybrid‑cobalt core-shell nano-catalyst (AF-CoFe2O4@CoSiOx) for the activation of PMS to degrade BPA with high efficiency. The comprehensive results from electron paramagnetic resonance technology, chemical probes and radical scavengers revealed the radical and non-radical pathways are co-existed in the system, and both of which could be promoted by accelerating the valence state cycling of Co(III)/Co(II) with the presence of acetate (Ac−). As an inherent component, the appropriate amount of Ac− facilitated the degradation of the electron-rich contaminants in practical FWL, especially BPA (100% removal). Furthermore, the magnetic core of AF-CoFe2O4@CoSiOx also enabled its good recycling with easy operation. The rational design of the core-shell nano-catalysts and the exploring of the overlooked important role of non-radical pathways stimulated by the inherent components in actual wastewater in this study offered a promising win-win strategy to realize BPA treatment in the future.

LBSUN310 Developmental Programming: Gestational Bpa Treatment Leads To Pancreatic Beta Cell Compromise

Abstract Developmental exposure to endocrine disrupting chemicals (EDC) such as bisphenol A (BPA) have been shown to be associated with many metabolic defects in humans. Studies in animals have documented detrimental effects of fetal exposure to BPA on metabolic variables such as insulin resistance, adiposity, and cardiac function. For instance, developmental exposure of sheep to bisphenol A (BPA), a ubiquitously present EDC, causes insulin resistance and compensatory hyperinsulinemia but the underlying mechanism of it is not fully understood. To determine if pancreatic hyperplasia or hypertrophy contributes to the hyperinsulinemic status and the ontogeny of these effects, pregnant Suffolk sheep were administered daily subcutaneous injections of BPA (0. 05, 0 .5 or 5 mg/Kg BW) in corn oil from days (D) 30-90 of gestation (term 147 days). Controls received corn oil during the same period. Pancreas were taken at Day 65 and 90 of gestation from control and 0.5mg/kg BPA (environmental exposure level)-treated female fetuses, and control and prenatal BPA-treated female offspring at 2 years of age (all 3 doses) during synchronized follicular phase of the cycle. Immunohistochemistry was used to determine beta cell number, size, and islet insulin content. In addition, to determine if the pancreas was fibrotic, islet collagen content was determined by Picro Sirius red staining and whole pancreas collagen content was measured with scroll collagen assay. Data were analyzed by ANOVA (Y2) and Students's t-test (D65 and D90), and magnitude of response by Cohen's Effect Size analysis. Findings showed large magnitude reduction of islet insulin content at day 65, significant decrease in islet insulin and beta cell count at D90 along with large magnitude decrease in pancreas/fetal weight. In contrast, in the Y2 sheep prenatal BPA treatment induced a large magnitude decrease in beta cell count (0. 05mg/kg dose group), a large magnitude increase in islet insulin content (5mg/kg dose group) and large magnitude increase in islet collagen content (all 3 BPA doses). The decrease in insulin in the D65 and D90 sheep along with the decrease in beta cells and pancreas/fetal weight at D90 indicates adverse developmental impact of BPA exposure on pancreatic beta cell differentiation. Increase in collagen accumulation in Y2 sheep likely contributes to the beta cell loss reflected as decrease in beta cell number seen in 0. 05 mg/kg dose of BPA. Absence of beta cell loss in 0.5 and 5mg/kg dose in the face of increased collagen is consistent with the nonmonotonic responses these EDCs manifest. Taken together, these results highlight the risks posed by developmental exposure to BPA on beta cell function and the corresponding risk for beta cell loss as animals age. Supported by NIH R01 grants ES016541 and ES030374 Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

RF22 | PMON09 BPA and BPF, but not BPS, alter pro- and anti-apoptotic transcript levels in granulosa cells, affecting cell viability.

Abstract Endocrine-disrupting compounds (EDCs) elicit adverse responses in the body, including the disruption of female reproductive functions. A common EDC is Bisphenol A (BPA), which is a frequently used plasticizer. Due to the negative effects of BPA on human health, production of BPA-free products using analogs, such as BPS and BPF, has increased; yet their effects are still largely unknown. Adequate oocyte maturation requires proper functioning of the surrounding environment, consisting of granulosa cells that impact oocyte competency. Granulosa cells are also susceptible to BPA disruption, affecting oocyte maturation and, ultimately, fertility. In our lab, we showed that BPA and BPS significantly increased apoptosis in bovine embryos through increased DNA fragmentation (Saleh et al., 2021). However, the apoptotic pathway used is not fully characterized. Thus, the aim of this study is to investigate how bisphenols affect granulosa cell viability and through which apoptotic pathway. In vitro cultured granulosa cells were exposed for 12 or 48 hrs to six treatment groups: control, vehicle, estradiol, BPA, BPS and BPF at a low dose (0.005 mg/mL) and at the BPA Lowest Observed Adverse Effect Level (LOAEL-0.05 mg/mL). Live cells were counted using trypan exclusion. A significant decrease in the number of live cells after BPA treatment at the LOAEL dose for 12 hrs was observed (P=0.02, n=9). mRNA expression of three proapoptotic (BAX, BAD, Casp9) and two antiapoptotic (HSP70 and BCl-2) genes was quantified by qPCR. A significant increase in BAX transcript levels after 12 hrs of exposure to BPA and BPF at the LOAEL dose (P=0.046, P= 0.033, n=6) as well as in BAD (P= 0.049, n=3) and Casp9 (P=0.049, n=4) levels after BPA exposure at the LOAEL dose was detected. Interestingly, at the 48 hr timepoint, a significant increase in BAD (P= 0.018, n= 9), BAX (P=0.002, n=10), and Casp9 (P=0.015, n=5) transcript levels was observed only following BPF treatment at the LOAEL dose. Despite expecting a decrease, both anti-apoptotic transcripts, at 12 and 48 hrs, showed increased levels following exposure to BPA and/or BPF at the LOAEL dose. This suggests an early first line of defense or shock response. Future protein analysis will help in further understanding these unexpected findings. To quantify apoptosis levels, flow cytometry together with Annexin V/PI staining was used. Results indicate that after 48 hrs of treatment, BPA at the LOAEL dose significantly increases late apoptosis (P=0.004, n=5) and necrosis (P=0.0014, n=5), while showing a significant decrease in the number of healthy cells (P=0.0007, n=5). Preliminary data also show a similar pattern after BPA treatment for 12 hrs. This research aims to further our knowledge of the mechanisms by which bisphenols affect oocyte competency and suggests that BPF might have equivalent potency and effects to BPA. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Endocrine disruptors affect the expression of estrogen receptor genes and proteins in the white cloud mountain minnow Tanichthys albonubes (Teleostei: Cyprinidae).

The endocrine disruptor chemicals (EDCs) are ubiquitous in the environment, and it has raised wide public concern because of the dangers of EDCs for living organisms and the environment. In order to comparatively study the effects of EDCs [17-α-ethinylestradiol (EE2), Bisphenol A (BPA) and Nonylphenol (NP)] on the expression of estrogen receptors (ERs: erα, erβ1, and erβ2) at mRNA and protein level, total 520 adult Tanichthys albonubes were exposed to E2, EE2, BPA and NP with three concentrations respectively: EE2 (1, 5, 25 ng/l), NP (10, 50, 250 μg/l), BPA (100, 500, 2,500 μg/l) for 28 days, E2 (2, 20, 200 ng/l) being as the positive control. After treatment, the brain, eye, gill, heart, liver, gut, kidney, muscle, testis, and ovary were collected, following by the real-time quantitative PCR (RT-qPCR) and western blot methods to detect the expression levels of erα, erβ1, and erβ2 in T.albonubes at mRNA and protein level. Our results showed that high expression of terα (t means T.albonubes), terβ1, and terβ2 were detected in liver, while terβ1 and terβ2 mainly expressed in the liver, intestine, kidney, muscle and testis. EE2, BPA, and NP treatment all up-regulated the expression of terα, terβ1, and terβ2 in the brain, liver, and testis, but with some variations. Similar to mRNA level, both TERα and TERβ were up-regulated by all the EE2, BPA, and NP treatment with dose-dependent effect. In conclusion, the responses of ERs of T.albonubes to the EDCs present measurability and susceptibility, which make it possible for T. albonubes to be an efficient biomarker to monitor and evaluate the pollution of endocrine disrupting chemicals in water environment.

Current progress in treatment technologies for plastic waste (bisphenol A) in aquatic environment: Occurrence, toxicity and remediation mechanisms

Bisphenol-A (BPA) is a type of endocrine disrupting compound (EDC) that is being widely used in the production of polycarbonate and epoxy resins. In the last few years, human exposure to BPA has been extensively high due to the continuous increment in the Annual Growth Rate (AGR) of the BPA global market. The presence and transportation of BPA in the environment could cause serious damage to aquatic life and human health. This paper reviewed the literature on the exposure and toxicity mechanisms of BPA and advanced analytical techniques for the detection of BPA in the environment and human beings. The study indicated that BPA can cause damaging effects on numerous tissues and organs, including the reproductive system, metabolic dysfunction, respiratory system, immune system and central nervous system. On the basis of reported studies on animals, it appears that the exposure of BPA can be carcinogenic and responsible for causing a variety of cancers like ovarian cancer, uterine cancer, prostate cancer, testicular cancer, and liver cancer. This review paper focused mainly on the current progress in BPA removal technologies within last ten years (2012–2022). This paper presents a comprehensive overview of individual removal technologies, including adsorption, photocatalysis/photodegradation, ozonation/advance oxidation, photo-fenton, membranes/nanofilters, and biodegradation, along with removal mechanisms. The extensive literature study shows that each technology has its own removal mechanism and their respective limitations in BPA treatment. In adsorption and membrane separation process, most of BPA has been treated by electrostatic interaction, hydrogen boning and π-π interations mechanism. Whereas in the degradation mechanism, O* and OH* species have played a major role in BPA removal. Some factors could alter the removal potential and efficiency of BPA removal. This review paper will provide a useful guide in providing directions for future investigation to address the problem of BPA-containing wastewater treatment.

Bisphenol S induces cardiovascular toxicity by disturbing the development of the common cardinal vein and myocardial contractility in zebrafish embryos

Bisphenol S (BPS) has been widely used as a substitute for bisphenol A in industrial manufacturing. However, the safety of BPS is controversial, and the mechanism by which BPS exerts cardiovascular toxicity remains unclear. In this study, zebrafish embryos, including wild-type zebrafish and transgenic (flk1:eGFP), (gata1:DsRed) and (cmlc2:eGFP) zebrafish at 2 h postfertilization (hpf), were exposed to BPS at concentrations of 1, 10 and 100 μg/L for 24, 48 and 72 h, respectively. The data showed that BPS accelerated the expansion of the common cardinal vein and inhibited lumen formation between 24 hpf and 72 hpf. Moreover, low-dose BPS disturbed cardiac muscle contraction by breaking the calcium balance in cardiac muscle cells according to the RNA-seq results. As a consequence, increased heart rate and irregular blood circulation were observed in the BPS treatment groups. This result suggested that BPS at environmental relevant concentrations caused cardiovascular toxicity during the development of zebrafish embryos, possibly being an important inducer of cardiovascular injury later in life. These findings provide insight into the rational and safe application of BPS.

Bisphenol A exposure causes testicular toxicity by targeting DPY30-mediated post-translational modification of PI3K/AKT signaling in mice

Bisphenol A (BPA), one of the chemicals with the highest volume of production worldwide, has been demonstrated to cause testicular toxicity via different pathways. However, there is little evidence concerning the mechanism of BPA exposure induced histone modification alterations, especially regarding the effect on the histone H3 lysine 4 (H3K4) epigenetic modification. Our results demonstrated a new epigenetic regulation of BPA exposure on testicular damage using both cell culture and mouse models. With BPA treatment, disordered and shrunken seminiferous tubules and poor sperm quality were observed in vivo, and mouse spermatogonial germ cell proliferation was inhibited in vitro. BPA attenuated PI3K expression inducing phospho-AKT inhibition in vivo and in vitro. DPY30 was the only downregulated subunit in BPA and MEK2206 (AKT inhibitor) treated cells, which contributed to reducing H3K4me3 recruitment at the PIK3CA transcriptional start site (TSS) in BPA treated cells. The toxicity caused by BPA exposure was relieved after the transduction of adenoviruses expressing DPY30 transgenes, which resulted in the stimulation of PI3K/AKT with H3K4me3 enriched at the PI3KCA TSS. DPY30 promoted cell glycolysis via AMPK and proliferation through AKT/P21. DPY30 was mainly located in the round and elongated spermatids for energy accumulation in mature sperm in AD-DPY30-treated mice which showed higher sperm quality. Overall, our results indicated that BPA exposure causes testicular toxicity through a DPY30-mediated H3K4me3 epigenetic modification, which serves to regulate the PI3K/AKT/P21 pathway.

Assessing the environmental sustainability of light emitting diodes and conventional blacklight lamps for the treatment of bisphenol-A in water

Ultraviolet (UV) water treatment techniques currently employ blacklight (UV-BL) lamps, which are energy intensive, short living and contain toxic materials, damaging the environment. Light emitting diodes (UV-LEDs) can offer an environmentally friendly alternative to UV-BLs, however their environmental impacts for water treatment have not been quantified yet. This study aims at investigating the environmental sustainability of UV-LEDs for removing bisphenol-A from water and compare it with UV-BL lamps. The life cycle assessment (LCA) methodology was utilised to estimate the process' environmental footprint. The functional unit adopted was the treatment of 1 L of water with initial 7.5 mg/L bisphenol-A concentration and 125 mg/L of titanium dioxide (TiO2) acting as a catalyst. UV-LED/TiO2 was found to have an environmental footprint of 61% less than UV-BL/TiO2. From a sensitivity analysis the environmental hotspots of the treatment process were the energy consumption and the photocatalytic reactors used. Therefore, three alternative scenarios investigating the use of solar photocatalysis, a renewable electricity mix and recyclable materials were explored to enhance the environmental performance of the treatment process. The results overwhelmingly favoured solar photocatalysis as the most environmentally sustainable treatment, leading to a 87.2% and 78.6% decrease of the environmental footprint of the UV-LED/TiO2 and the UV-BL/TiO2 treatment process, respectively. Using a renewable electricity mix, representative of Scotland's renewable output, a decrease of 41.5% (from 198.3 to 116.0 μPt) and 15.7% (from 517.2 to 435.9 μPt) for the UV-LED/TiO2 and UV-BL/TiO2, respectively, was observed. Beginning with the most environmentally sustainable, the treatment processes ranked in the following order: solar/TiO2 > UV-LED/TiO2 renewable electricity mix > UV-LED/TiO2 > UV-BL/TiO2 renewable electricity mix > UV-BL/TiO2, indicating that UV-LED systems driven by renewable electricity could be feasible for 24/7 large-scale wastewater treatment systems.

Activated peroxymonosulfate with ferric chloride-modified biochar to degrade bisphenol A: Characteristics, influencing factors, reaction mechanism and reuse performance

Water environment pollution caused by a large amount usage of bisphenol A (BPA) in industry has attracted widespreadattention, since BPA may destroy the endocrine system of organisms and even the human body. Peroxymonosulfate (PMS) catalyzed by biochar (BC) for the removal of emerging pollutants (including BPA) from water body has entered the researcher's field of vision. A ferric chloride- modified rice husk BC was prepared via one pot method and characterized by BET, SEM, XPS, and Raman spectroscopy. A series of batch experiments were conducted to investigate the performance, influencing factors, and reaction mechanism of BC/PMS system for the degradation of BPA. The results showed that more than 97 % of BPA was removed with 1.0 g/L F2BC3 and 1.6 g/L PMS from the artificial solution containing 20 mg/L BPA within 150 min at different pH (3, 6, and 10); the degradation of BPA was not associated with humic acid (HA), was inhibited by HCO3−, NO3−, H2PO4−, and Cl− (at low concentration), and was promoted by Cl− (at high concentration) based on the concentration range set in this study; the removal rate of BPA by F2BC3/PMS decreased from 94.3 % to 84.8 % after four cycles of F2BC3, which meant stable performance was demonstrated. It could be confirmed that BPA was degraded into intermediates and final products H2O and CO2 via co-attack of major free radicals (SO4−, OH, and O2−) and minor non-radical 1O2. Therefore, F2BC3/PMS system could be considered as a potential process for the treatment of BPA.