Low Concentrations Of Bisphenol A Research Articles

Safe concentration, unsafe effects: Impact of BPA on antioxidant function in the hepatopancreas and ovarian gene expression in oriental river prawns (Macrobrachium nipponense)

This study investigated the effects of Bisphenol A (BPA), a common endocrine-disrupting chemical, on the antioxidant enzyme activities in the hepatopancreas and the expression of genes related to ovarian development in oriental river prawns (Macrobrachium nipponense). The 24hLC50 and 48hLC50 values for BPA were 80.59 mg/L and 63.90 mg/L, respectively, with a safe concentration of 12.06 mg/L. Prawns were exposed to low (4.85 mg/L), safe (12.06 mg/L), and high (30.00 mg/L) concentrations of BPA for 10 days to measure enzyme activities, and for 20 days followed by 7 days in BPA-free water to measure gene expression.Short-term exposure (12 h, 1d, 3d) to low concentration BPA did not significantly affect superoxide dismutase (SOD) activity in the hepatopancreas (P > 0.05), but long-term exposure (6d, 10d) significantly reduced SOD activity (P < 0.05). Catalase (CAT) activity showed no significant changes throughout the low concentration exposure period (P > 0.05). At safe and high concentrations, SOD and CAT activities significantly decreased after 12 h of exposure (P < 0.05).BPA affected heat shock protein 90 (HSP90) expression in the ovary, with low concentration BPA significantly upregulating HSP90 after 1 day (P < 0.05), but returning to normal levels after 10 and 20 days. At the safe concentration, HSP90 was significantly upregulated at all three sampling points (1d, 10d, 20d) (P < 0.05), while high concentration exposure led to significant upregulation only on day 10 (P < 0.05).Low concentration BPA had no significant effect on Cathepsin B (CB) and Cathepsin L (CL) gene expression in the ovaries (P > 0.05). However, safe concentration exposure promoted CB expression on days 1, 10, and 20 (P < 0.05), while high concentration exposure significantly increased CB expression on day 1 (P < 0.05), with levels returning to normal on days 10 and 20. CL expression significantly increased after 20 days of exposure to both safe and high concentrations (P < 0.05). Gene expression levels in the ovaries returned to normal after transfer to BPA-free water, with HSP90 and CB normalizing by day 1, and CL by day 7.These results indicate that even safe concentrations of BPA impose stress on the hepatopancreas and increase the expression of HSP90, CB, and CL genes in the ovaries, affecting ovarian development. And, these effects are reversible within a certain period after the removal of BPA.

Acute Bisphenol-A exposure triggers superoxide-nitric oxide imbalance and immunocompetence impairment of Eisenia fetida earthworm

Bisphenol-A (BPA) is an endocrine-disrupting molecule associated with the risk of several non-transmissible chronic diseases. We postulated that BPA triggers oxidative alterations, altering immunocompetence and contributing to physiological dysfunction. To evaluate the effects of BPA on the oxidative and immune system, Californian earthworms were reared in a culture medium containing different BPA concentrations for 24 and 72 h. Coelomocytes were used to evaluate the effects of BPA on oxidative markers, cellular proliferation, and apoptosis, and immunocompetence effects were investigated by yeast-exposure assay and the modulation of genes related to immune response. Low BPA concentrations induced coelomocyte proliferation, imbalanced superoxide/NO levels, higher micronucleus frequency, and apoptosis. BPA also induced Amp1 gene overexpression and a low efficiency of dead yeast capture. The association between DNA damage and changes in innate immune metabolism could be related to the action of BPA, which is associated with the risk of physiological disturbances and non-transmissible chronic diseases.

Putative adverse outcome pathway development based on physiological responses of female fathead minnows to model estrogen versus androgen receptor agonists

Several adverse outcome pathways (AOPs) have linked molecular initiating events like aromatase inhibition, androgen receptor (AR) agonism, and estrogen receptor (ER) antagonism to reproductive impairment in adult fish. Estrogen receptor agonists can also cause adverse reproductive effects, however, the early key events (KEs) in an AOP leading to this are mostly unknown. The primary aim of this study was to develop hypotheses regarding the potential mechanisms through which exposure to ER agonists might lead to reproductive impairment in female fish. Mature fathead minnows were exposed to 1 or 10 ng 17α-ethynylestradiol (EE2)/L or 10 or 100 µg bisphenol A (BPA)/L for 14 d. The response to EE2 and BPA was contrasted with the effects of 500 ng/L of 17β-trenbolone (TRB), an AR agonist, as well as TRB combined with the low and high concentrations of EE2 or BPA tested individually. Exposure to 10 ng EE2/L, 100 µg BPA/L, TRB, or the various mixtures with TRB caused significant decreases in plasma concentrations of 17β-estradiol. Exposure to TRB alone caused a significant reduction in plasma vitellogenin (VTG), but VTG was unaffected or even increased in females exposed to EE2 or BPA alone or, in most cases, in mixtures with TRB. Over the course of the 14-d exposure, the only treatments that clearly did not affect egg production were 1 ng EE2/L and 10 µg BPA/L. Based on these results and knowledge of hypothalamic–pituitary–gonadal axis function, we hypothesize an AOP whereby decreased production of maturation-inducing steroid leading to impaired oocyte maturation and ovulation, possibly due to negative feedback or direct inhibitory effects of membrane ER activation, could be responsible for causing adverse reproductive impacts in female fish exposed to ER agonists.

Bisphenol A has a sex-dependent disruptive effect on hepatic lipid metabolism in zebrafish

Bisphenol A (BPA) is an endocrine disruptor that has adverse effects on lipid metabolism. However, most of the current studies on the effects of BPA on lipid metabolism in fish have focused on middle- and short-term exposure tests. The aim of this study was to investigate the effects of long-term BPA exposure on liver lipid metabolism in zebrafish. Post-fertilization embryos were exposed to environmentally relevant concentrations of BPA for 120 days, and the changes in triglyceride (TG), total cholesterol (TC) levels, and gene expression related to liver lipid metabolism were investigated in both male and female fish. The results showed that long-term exposure to BPA led to lipid deposition in liver, and there was a sex difference. In the liver of female fish, there was higher lipid transport and synthesis at low concentration of BPA, while overall metabolic levels were increased at high concentration of BPA. In contrast, BPA showed a dose-dependent effect on the lipid deposition in male fish. The expression of mRNA of TG transport-related and lipid synthesis-related genes was significantly up-regulated and the expression of genes related to lipid catabolism, was significantly down-regulated with increasing BPA dose. Taken together, our results indicate that long-term exposure to BPA can increase lipid deposition in a gender-specific manner. This may be due to the different responses of lipid metabolism related genes to BPA in male and female zebrafish. These results will provide a new reference for a deeper understanding of the ecotoxicological effects of BPA on aquatic animals.

Sensitivity and reusability of a simple microbial fuel cell-based sensor for detecting bisphenol A in wastewater

Polycarbonate plastic processing wastewater contains high concentrations of bisphenol A (BPA), requiring a real-time technology to monitor wastewater containing BPA. Since the activity of electrogenic microorganisms on the anode surface of the microbial fuel cell (MFC) sensor is inhibited by exposure to contaminants, the toxicity of contaminants in wastewater can be determined by observing the variation in voltage output from the MFC sensor. The simple MFC sensor that is developed in this work exhibited a significant decrease in voltage output in BPA-containing wastewater concentration of 5–100 mg/L. Sensitivity analysis revealed that the voltage change (ΔV) was strongly correlated with the BPA concentration, with R2 as high as 0.97. This study was the first to investigate the number of repeated uses of the MFC sensor, using sodium acetate as the regeneration solution for the MFC sensor, leading to a successful recovery of detection performance. However, as the number of uses increased (up to the third or fourth use), the ΔV of the MFC sensor for BPA gradually decreased and the sensitivity decreased significantly from 0.238 mV/mg/L to 0.027 mV/mg/L. In the low BPA concentration range (≦20 mg/L), the MFC sensor can be reused up to 5 times, demonstrating that the proposed MFC sensor can be reused. Microorganisms contribute to the power generation of the MFC sensor, which can be exploited in the detection of pollutants, enabling the determination of wastewater toxicity and providing early warnings of thereof. Conventional MFC sensors are complex and lack the ability to explore repeated use, so they are not easily applied to actual wastewater detection. The proposed MFC sensor has many advantages such as simplicity, rapid detection, and reusability, solving the problem of the high cost of using disposable MFC sensors and making them feasible for practical use.

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.

Sex-specific associations between urinary bisphenols concentrations during pregnancy and problematic child behaviors at age 2 years

Effects of prenatal bisphenol A (BPA) exposure on child behavior are mixed with some reports suggesting increased problematic behaviors in girls (e.g., aggression and emotional reactivity) and in boys (i.e., externalizing behaviors), while other reports suggest decreased problematic behaviors in girls. Little is known about the potential impact of pregnancy bisphenol S (BPS) exposure on child behavior. In a prospective cohort study (n = 68), five maternal spot urine samples collected across pregnancy were pooled and analyzed for BPA and BPS. Child behavior at 2 years was assessed using the Child Behavior Checklist (CBCL). Linear regression models were used to assess associations between bisphenols concentrations and both composite and syndrome CBCL scales. Exposure x child sex interactions were included in addition to their main effects and sex-stratified analyses were conducted. Models were adjusted for maternal age, number of siblings, and child age at CBCL intake. Mean maternal age was 29.7 years. Most women were White (88%), had an annual household income ≥$50,000 (66%), and at least a college degree (81%). Median concentrations were 1.3 ng/mL (range 0.4–7.2) for BPA and 0.3 ng/mL (range 0.1–3.5) for BPS. Sex modified the relationship between BPA and scores on several syndrome scales—anxious-depressed, aggressive, and sleep problems—where the association was consistently inverse in males in lower BPA concentrations, and positive (more reported behavior problems) among girls in the higher BPA group. Higher BPS was associated with more problematic internalizing behaviors among girls but not boys, and sex modified the relationship between BPS and emotionally reactive behaviors (Pinteraction = 0.128), with sex-specific estimates revealing more emotionally reactive behaviors among girls (expβ = 3.92 95% CI 1.16, 13.27; P = 0.028) but not boys. Findings were mixed overall, but one notable finding was that BPS, a replacement for BPA, was associated with increased problematic behaviors. There is a need for replication of findings due to our small sample size.

Morphological changes and biochemical reaction of Ulva rigida in response to the toxic effect of bisphenol A under experimental conditions

The large-scale worldwide production and consumption of bisphenol A (BPA) has resulted in the ubiquitous presence of this chemical in aquatic ecosystems. Primary producers such as marine macroalgae can be successfully used for monitoring in order to determine the environmental risk from organic pollutants. The article is based on new experimental data obtained by the authors in the study of the sensitivity of the green marine benthic algae Ulva rigida to the impact of various concentrations of BPA was conducted. Exposure to BPA led to structural and functional changes in the Ulva samples: growth rate, cell size, and photosynthetic pigment content. In concentrations from 40 to 100 mg/L, a destructive effect from BPA on the Ulva was observable within 24–48 h, taking the form of complete chloroplast discoloration occurring in 100% of its cells. A dose-dependent stimulating effect of low concentrations of BPA on the growth of Ulva was also noted. As compared with the control, the disc area of Ulva in a medium with a BPA concentration of 0.1 mg/L almost doubled within 30 days, while at 5 mg/L, it increased by only 21%. Changes in chlorophyll a and b content were observed in the first hours of BPA exposure. The pigment content in the Ulva decreased under the influence of BPA both at an impact concentration of 100 mg/L and a low concentration of 0.01 mg/L. The sensitivity to bisphenol А contamination of the U. rigida in different regions may vary.

The response of anaerobic ammonium oxidation process to bisphenol-A: Linking reactor performance to microbial community and functional gene.

As a typical endocrine disruptor, bisphenol A (BPA) has been widely detected in various water bodies. Although the influence of BPA on traditional biological treatment system has been investigated, it is not clear whether it has potential impact on anaerobic ammonium oxidation (anammox) process. The short- and long-term influences of BPA on reactor operational performance, sludge characteristics and microbial community were investigated in this study. Results revealed that 1 and 3 mg L-1 BPA exhibited a limited adverse impact on granular sludge reactor performance. However, exposure of sludge under 10 mg L-1 BPA would cause an obvious inhibition on nitrogen removal rate from 10.3 ± 0.2 to 7.6 ± 0.4 kg N m-3 d-1. BPA would affect granular sludge metabolic substance excretion and lead to effluent dissolved organic content increase. Both the microbial community and redundancy analysis showed that BPA exhibited a negative influence on Ca. Kuenenia but a positive correlation with SBR1031. Low BPA concentration appeared a limited impact on functional genes while 10 mg L-1 BPA would cause decline of hzsA and hdh abundances. The results of this work might be valuable for in-depth understanding the potential influence of endocrine disruptor on anammox sludge.

The Current Findings on the Impact of Prenatal BPA Exposure on Metabolic Parameters: In Vivo and Epidemiological Evidence.

Metabolic syndrome (MS) is a multifactorial disease entity and is not fully understood. Growing evidence suggests that early exposure to bisphenol A (BPA) is a significant risk factor for the development of metabolic diseases. BPA is a monomer used in the manufacturing of polycarbonate plastics, thermal receipt paper, and epoxy resins. Owing to its widespread use, BPA has been detected in human fluids and tissues, including blood, placental breast milk, and follicular fluid. In the present review, we aimed to review the impact of prenatal exposure to different doses of BPA on metabolic parameters as determined by in vivo and epidemiological studies. The PubMed, Scopus, and Web of Science electronic databases were searched to identify articles published during a period of 15 years from 2006 to 2021, and 29 studies met the criteria. Most studies demonstrated that prenatal exposure to low BPA concentrations correlated with alterations in metabolic parameters in childhood and an increased risk of metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM), in adulthood. Therefore, prenatal exposure to low doses of BPA may be associated with an increased risk of obesity and T2DM in a sex-specific manner.

Bisphenol A exposures and hormone concentrations in a cohort of women receiving aromatase inhibitor therapy for breast cancer.

e12535 Background: Bisphenol A (BPA), a widely used chemical in plastics production, has been shown to have estrogenic activity, although it is unclear whether BPA exposure alters effectiveness of aromatase inhibitor (AI) treatment among women with breast cancer. In vitro studies have indicated that at higher concentrations (≥10-4 μM), BPA inhibits aromatase expression and activity, whereas at environmentally relevant concentrations (≤10-8 μM), BPA increases aromatase expression and activity. Few in vivo studies have investigated the association between BPA exposure and estrogen concentrations among non-pregnant women. This pilot study among post-menopausal women receiving AI therapy evaluated whether BPA is detectable in participants’ urine, and the association between BPA and hormone concentrations. Methods: This study was ancillary to a larger intervention study (ClinicalTrials.gov NCT01509079), and participants provided informed consent for this ancillary study under a protocol approved by the institutional review boards of Park Nicollet Institute/HealthPartners and the University of Minnesota. AI adherence during the 4 weeks prior to the baseline visit was monitored through weekly diaries. Participants were instructed to collect spot urine collections in sterile, BPA-free polypropylene containers in the 24 hours prior to the baseline study visit. Serum hormone concentrations were measured using serum collected at the baseline study visit. The Breast Cancer Prevention Trial - Musculoskeletal Symptom (BCPT-MS) scale was used to assess AI-associated musculoskeletal syndrome symptoms at the baseline study visit. Results: Fourteen women agreed to participate in the pilot study, however one participant’s data was excluded due to substances interfering with BPA measurement. BPA was detected in urine from all 13 remaining participants. Geometric mean urinary BPA concentration (1.55 mcg/g creatinine, 95% confidence interval (CI): 0.98-2.45) was higher than concentrations reported for females (1.36 mcg/g creatinine, 95% CI: 1.23-1.51) in the 2013-14 National Health and Nutrition Examination Survey biomonitoring data. Age, body mass index, and percent body fat did not differ between women above or below the study median urinary BPA concentrations (1.49 ng/mL). Women with BPA concentrations &gt;1.49 ng/mL had consistently lower serum estrone (5.0 vs. 7.0 pg/mL, p=0.15), estradiol (2.8 vs. 3.6 pg/mL, p=0.04), and testosterone (21.5 vs 23.8 ng/dL, p=0.28) concentrations compared to women with lower BPA concentrations. No statistically significant differences in BCPT-MS scores were observed between women with higher vs. lower urinary BPA concentrations. Conclusions: These preliminary findings suggest that BPA exposures may work in concert with AIs to lower serum estrogen levels. However, further research is needed to confirm these findings.

Low concentrations of bisphenol A promote the activation of the mitochondrial apoptotic pathway on Beta-TC-6 cells via the generation of intracellular reactive oxygen species and mitochondrial superoxide.

Τhe natural history of type 2 diabetes mellitus is characterized by a progressive loss of pancreatic beta cell function and insulin resistance. Bisphenol A (BPA) is an endocrine-disrupting chemical that is used widely in industry; people are exposed to BPA and its products daily. Studies have delineated that BPA alters the function of pancreatic beta cells. Herein, we examined the effect of low doses of BPA on pancreatic beta cell viability and apoptosis and we tried to elucidate the mechanisms involved in these processes. Beta-TC-6 (ATCC® CRL-11506™) cells were cultured with a medium containing the following dilutions of BPA: 0.002, 0.02, 0.1, 0.2, 2 μΜ up to 72 h. We examined the viability and adenosine triphosphate (ATP) levels of cells. Then, we measured apoptosis, cell cycle, and insulin levels. We quantified the levels of proteins implicated in the mitochondrial pathway of apoptosis; and finally, we quantified the intracellular reactive oxygen species and mitochondrial superoxide. We found that the exposure of Beta-TC-6 cells to BPA results in a decrease in cell viability, ATP levels, and an increase in insulin levels. We found an increase in apoptosis levels and a decrease in cell cycle levels. In addition, we provide evidence of the levels of apoptotic proteins. Finally, we found an increase in the cellular reactive oxygen species and mitochondrial superoxide production. Exposure to low concentrations of BPA triggers the mitochondrial pathway of apoptosis via the generation of intracellular reactive oxygen species and mitochondrial superoxide on Beta-TC-6 cells in a dose-dependent way.

Effects of bisphenol A exposure on proteins tyrosine phosphorylation in mammalian sperm

Bisphenol A (BPA) is a synthetic estrogen compound, which widely exists in the environment, interferes with mammalian endocrine and affects the function of reproductive system of males. Taking fresh sperm of boar, 17 ℃ preservation boar sperm, and mouse sperm as test materials, we examined the effects of BPA (0, 0.1,1,10,100 μmol∙L-1) on proteins tyrosine phosphorylation in sperm and the molecular mechanism by using wes-tern blot (WB) and immunofluorescence techniques coupled to in vitro culture method. The results showed that low BPA concentration (0.1, 1 μmol∙L-1) markedly accelerated the protein tyrosine phosphorylation of fresh boar capacitated sperm. However, the tyrosine phosphorylation of boar sperm decreased in high BPA concentration (10, 100 μmol∙L-1). The tyrosine phosphorylation of the mouse sperm raised with the increases of BPA concentration. Moreover, BPA affected different kinds of proteins related to tyrosine phosphorylation modification of porcine and mouse sperm capacitation, suggesting that the effect of BPA exposure on mammalian sperm was species-specific. Furthermore, the results of immunofluorescence showed that the effects of BPA on protein tyrosine phosphorylation in sperm mainly occurred in the middle and principal piece of flagellum.

Potential Role of Agrimonia eupatoria L. Extract in Cell Protection Against Toxicity Induced by Bisphenol A

Abstract The aim of this study is to reveal the potentially protective role of ethanolic extract of agrimony (Agrimonia eupatoria L.) against the cytotoxic effect of bisphenol A (BPA) in vitro, using an intestinal porcine epithelial cell line (IPEC-1). The cells were exposed to different concentrations of BPA: 12.5, 25, 50, 100, and 200 µg.ml–1 alone and in combination with agrimony extract (250 µg.ml–1). The proliferative cell response was monitored for 72 h by a xCELLigence system or real-time cell analyser (RTCA), recorded as the cell index (CI) and expressed as a proliferative activity (% PA) compared to the control cells without treatment. The metabolic activity was measured by a MTS colorimetric test, performed after 48 h of treatment with the tested substances. The cytotoxic effect on cells exposed to BPA alone, in comparison to the control cells without treatment, was observed in both assays (P &lt; 0.0001). It was confirmed that BPA reduces both the metabolic activity and the proliferation of cells. After the cell treatment with agrimony, the metabolic activity had increased to reach over the control (101.52 %), while reducing the proliferation of the cells. The protective role of agrimony against cytotoxicity caused by BPA was observed after cell treatment with agrimony in combination with lower concentrations of BPA (12.5; 25 and 50 µg.ml–1). The slight improvement in the adherence was observed in cells treated with these combinations, in comparison to the cells treated with BPA alone. On the other hand, the metabolic activity was slightly improved in cells treated with a combination of agrimony and BPA at higher concentrations (50 a 100 µg.ml–1). This supported our assumption that agrimony can protect a model organism against cytotoxicity caused by BPA.

The Enzymatic and Non-Enzymatic Antioxidant System Response of the Seagrass Cymodocea nodosa to Bisphenol-A Toxicity.

The effects of environmentally relevant bisphenol A (BPA) concentrations (0.3, 1 and 3 μg L−1) were tested at 2, 4, 6 and 8 days, on intermediate leaves, of the seagrass Cymodocea nodosa. Hydrogen peroxide (H2O2) production, lipid peroxidation, protein, phenolic content and antioxidant enzyme activities were investigated. Increased H2O2 formation was detected even at the lowest BPA treatments from the beginning of the experiment and both the enzymatic and non-enzymatic antioxidant defense mechanisms were activated upon application of BPA. Elevated H2O2 levels that were detected as a response to increasing BPA concentrations and incubation time, led to the decrease of protein content on the 4th day even at the two lower BPA concentrations, and to the increase of the lipid peroxidation at the highest concentration. However, on the 6th day of BPA exposure, protein content did not differ from the control, indicating the ability of both the enzymatic and non-enzymatic mechanisms (such as superoxide dismutase (SOD) and phenolics) to counteract the BPA-derived oxidative stress. The early response of the protein content determined that the Low Effect Concentration (LOEC) of BPA is 0.3 μg L−1 and that the protein content meets the requirements to be considered as a possible early warning “biomarker” for C. nodosa against BPA toxicity.

Early developmental exposure to bisphenol A and bisphenol S disrupts socio-cognitive function, isotocin equilibrium, and excitation-inhibition balance in developing zebrafish

Dysregulation of the oxytocinergic system and excitation/inhibition (E/I) balance in synaptic transmission and neural circuits are common hallmarks of various neurodevelopmental disorders. Several experimental and epidemiological studies have shown that perinatal exposure to endocrine-disrupting chemicals bisphenol A (BPA) and bisphenol S (BPS) may contribute to a range of childhood neurodevelopmental disorders. However, the effects of BPA and BPS on social-cognitive development and the associated mechanisms remain largely unknown. In this study, we explored the impacts of early developmental exposure (2hpf-5dpf) to environmentally relevant concentrations of BPA, and its analog BPS (0.001, 0.01, and 0.1 μM), on anxiety, social behaviors, and memory performance in 21 dpf zebrafish larvae. Our results revealed that early-life exposure to low concentrations of BPA and BPS elevated anxiety-like behavior, while fish exposed to higher concentrations of these chemicals displayed social deficits and impaired object recognition memory. Additionally, we found that co-exposure with an aromatase inhibitor antagonized BPA- and BPS-induced effects on anxiety levels and social behaviors, while the co-exposure to an estrogen receptor antagonist restored recognition memory in zebrafish larvae. These results indicate that BPA and BPS may affect social-cognitive function through distinct mechanisms. On the other hand, exposure to low BPA/BPS concentrations increased both the mRNA and protein levels of isotocin (zebrafish oxytocin) in the zebrafish brain, whereas a reduction in its mRNA level was observed at higher concentrations. Further, alterations in the transcript abundance of chloride transporters, and molecular markers of gamma-aminobutyric acid (GABA) and glutamatergic systems, were observed in the zebrafish brain, suggesting possible E/I imbalance following BPA or BPS exposure. Collectively, the results of this study demonstrate that early-life exposure to low concentrations of the environmental contaminants BPA and BPS can interfere with the isotocinergic signaling pathway and disrupts the establishment of E/I balance in the developing brain, subsequently leading to the onset of a suite of behavioral deficits and neurodevelopmental disorders.

Analysis of the Toxic Effects of Bisphenol A on the Groups of Vertebrate Animals: a Comprehensive Review of Research 2015-2021

The toxic effects of Bisphenol A (BPA) have been studied in individual experimental animals under different conditions. However, without a systematic approach, it is difficult to compare and analyse the results because of differences in doses (concentration), dosing periods (exposure), research methods, and the effects of BPA. We systematically compared and analysed recent research (between 2015 and 2021) that examined the effects of BPA on individual experimental vertebrates (fishes, amphibians, birds, and mammals). We divided the experiments into two categories: experiments on fish and amphibians by indirect administration, and experiments on birds and mammals by direct administration. The deleterious effects of exposure to BPA were classified into two types: morphological and anatomical effects, and physiological and neurocognitive effects. Experimental animals that had less weight, were younger, and were farther away from humans in evolutionary relationships, showed toxic effects even if they were exposed to low concentrations of BPA in the short term. Long-term administration of a small amount of BPA and short-term administration of a large amount of BPA also showed severe toxic effects. When the parents absorbed BPA during puberty, just before fertilisation, or during pregnancy, toxic effects were transmitted from dosed parents to offspring. With increasing amounts of BPA production and waste, there is a growing possibility that animals in various ecosystems will be exposed to BPA. Therefore, it is necessary to identify the harmful effects of BPA on various animals and the conditions under which it affects them. We hope that the results reported here will contribute to the development of standardized study designs for BPA research, to ensure that results can be more readily compared.

Polychaetes as bioindicators of environmental pollution: Impact of bisphenol A on the reproduction rate of Ophryotrocha diadema (Åkesson, 1976) (Eunicida: Dorvilleidae)

Bisphenol A (BPA) is one of the most used additives in the production of many plastic products and may be released into the environment by commonly used products, such as food containers and polycarbonate bottles. BPA is recognized as an endocrine disruptor able to produce adverse effects on the reproduction system of benthonic and pelagic species. Polychaetes of the genus Ophryotrocha are small worms living amongst the interstitial fauna in nutrient-rich and polluted habitats. Owing to easy rearing in the laboratory and short generation times, this species is a useful model organism for studying different biological aspects. This study describes the effects of different BPA concentrations on egg production in Ophryotrocha diadema. We tested six different concentrations of BPA in a 5-week experiment. Strong negative correlation between BPA concentrations and the number of eggs produced was found. The t-test revealed a significant reduction in egg production after exposure to BPA concentrations over 1461.1 μg/L. The latter concentration value is higher than that observed in the marine environment, although for many species of crustaceans, echinoderms and isopods, the impairment of reproductive function was observed even at much lower BPA concentrations.

Co-occurring Environmental Stressors have Emerging Impacts on Sensory-Motor Behavior.

Anthropogenic activities often lead to alterations in the natural environment via multiple routes. Simultaneous occurrence of interacting environmental perturbations may influence animals via more complex pathways than when being exposed to environmental stressors discretely. In our study, we investigated the interactive effects of poor visual environment and exposure to an environmentally realistic concentration of a common contaminant on the behavior of larval zebrafish, Danio rerio. Specifically, we tested the sensory-motor behavior of zebrafish larvae by exposing them to low-light conditions and a low concentration of bisphenol-A (BPA) for 7 days postfertilization. We found that zebrafish exposed to both BPA and low-light conditions had significantly weaker response to a moving-visual cue. However, those exposed to only one of these treatments did not have altered response to visual cues. Since the response to a moving, visual cue involves locomotion, we also examined the distance they traveled as a proxy for activity level of individuals across treatments. However, the distance traveled by individuals did not significantly differ across treatments, suggesting that the differences in response are linked to visual sensory pathways. Here, we emphasize that the adverse effects of environmental stressors, particularly of those that occur at environmentally relevant concentrations, may emerge only when they co-occur with another environmental stressor. These findings highlight the need to incorporate multiple environmental stressors to comprehensively assess impacts that human activities have on behavioral strategies of animals.

Immunohistochemical expression of aromatase cyp19a1a and cyp19a1b in the ovary and brain of zebrafish (Danio rerio) exposed to different concentrations of bisphenol A.

Bisphenol A (BPA) is used to produce plastic and plastic derived products in multitude of daily utensils, being one of the industrial compounds most widely used. This endocrine disrupting chemical (EDCs) is a well-known environmental pollutant released into the aquatic environment from industrial wastewater, sewage sludge or landfill leachate. Aromatases are considered potential targets of EDCs with characteristics that make them suitable biomarkers of exposure to their effects. The main objective of our study was to evaluate the expression of cyp19a aromatase as a toxicological endpoint after BPA exposure through the identification and assessment of alterations of the main cells responsible for cyp19a1a and cyp19a1b expression in the zebrafish ovary and brain using different concentrations of BPA in water. Immunohistochemistry was used to analyze the expression of these enzymes in female zebrafish exposed and not exposed to different concentrations of BPA (1, 10, 100 and 1000μg / L) in water (n=6/group) for 14 days. The results obtained in this study showed that the cyp19a aromatase system, involved in the synthesis of steroid compounds, is specially located in distinct oocyte stages in the ovary (cyp19a1a) and in radial glial cells of the brain (cyp19a1b). An overexpression of these aromatases was observed after BPA exposure in zebrafish, peaking from a concentration of 10µg/L and showing to be good biomarkers of exposure to identify the early effects of low BPA concentrations. To our knowledge, this study is the first to localize and quantify the expression of cyp19a1a and cyp19a1b in the cells of brain and ovary after fish exposure to different BPA concentrations in water.