Effects Of Bisphenol A Research Articles

Taurine protection attenuates bisphenol-A-induced behavioral, neurochemical, and histopathological alterations in male rats.

Due to the continuous exposure to bisphenol-A (BPA), the current study was conducted to evaluate taurine's neuroprotective action against BPA's adverse effect on the brain. Rats were grouped into control, BPA-treated rats, and taurine + BPA-treated rats. At the end of the 35-day treatment period, the memory of the rats was evaluated using the novel object test and the Y-maze test. An open-field test was used to measure motor activity. The changes in monoamines, monoamine oxidase (MAO), acetylcholinesterase (AChE), Na+,K+,ATPase, oxidative stress, caspase-3, and histopathology were evaluated in the cortical and hippocampal tissues of all groups. Data analysis by ANOVA revealed that BPA treatment induced motor hyperactivity and short- and long-term memory impairment. In the cortex, BPA decreased serotonin (5-HT), norepinephrine (NE), MAO, Na+,K+,ATPase, and nitric oxide (NO) and increased dopamine (DA), AChE, lipid peroxidation (MDA), glutathione (GSH), and caspase-3. In the hippocampus, BPA increased 5-HT, DA, NE, MAO, AChE, MDA, NO, GSH, and caspase-3 and decreased Na+,K+,ATPase. These neurochemical changes were accompanied by significant histopathological alterations. Taurine treatment prevented memory impairment and motor hyperactivity induced by BPA. Taurine attenuated the neurochemical changes, oxidative stress, and caspase-3 level. Taurine improved the histopathological change induced by BPA. In conclusion, taurine significantly prevented BPA-induced cognitive deficits, motor coordination impairments, neurotransmitter imbalances, histopathological alterations, oxidative stress, and apoptosis.

Impact of Ex Vivo Bisphenol A Exposure on Gut Microbiota Dysbiosis and Its Association with Childhood Obesity

Dietary exposure to the plasticiser bisphenol A (BPA), an obesogenic and endocrine disruptor from plastic and epoxy resin industries, remains prevalent despite regulatory restriction and food safety efforts. BPA can be accumulated in humans and animals, potentially exerting differential health effects based on individual metabolic capacity. This pilot study examines the impact of direct ex vivo BPA exposure on the gut microbiota of obese and normal-weight children, using 16S rRNA amplicon sequencing and anaerobic culturing combined methods. Results showed that direct xenobiotic exposure induced modifications in microbial taxa relative abundance, community structure, and diversity. Specifically, BPA reduced the abundance of bacteria belonging to the phylum Bacteroidota, while taxa from the phylum Actinomycetota were promoted. Consistently, Bacteroides species were classified as sensitive to BPA, whereas bacteria belonging to the class Clostridia were identified as resistant to BPA in our culturomics analysis. Some of the altered bacterial abundance patterns were common for both the BPA-exposed groups and the obese non-exposed group in our pilot study. These findings were also corroborated in a larger cohort of children. Future research will be essential to evaluate these microbial taxa as potential biomarkers for biomonitoring the effect of BPA and its role as an obesogenic substance in children.

Maternal–Foetal Effects of Exposure to Bisphenol A: Outcomes and Long-Term Consequences

Exposure to bisphenol A (BPA), one of the most widely produced plasticisers, can have a major effect on the growing embryo and the mother during pregnancy; as this is the most vulnerable period, the cutoff established in the legislation does not take this factor into account. Thus, this narrative review aims to highlight the consequences for the foetus and the pregnant woman of maternal and foetal exposure to BPA by analysing epidemiological and experimental studies on humans. Extensive research has examined the effects of BPA on several systems outcomes. Specifically, BPA exposure affects the immune system of the offspring and promotes the development of respiratory diseases, including asthma and wheezing. Moreover, BPA has been negatively associated with children’s neurodevelopment, leading to behavioural changes; autism; and reproductive changes, mainly deviations in anogenital distance, sexual hormone levels and sexual maturation, which can result in infertility. Furthermore, in mothers, BPA exposure may be linked to pre-eclampsia and gestational diabetes mellitus and affects birth parameters, leading to a higher risk of preterm delivery, shorter birth lengths and lower birth weights, although the results were not always consistent. These results demonstrate the urgent need for stricter legislation banning the use of BPA during pregnancy to reduce the hazards to the health and development of the foetus and the unborn child.

Transformation fate of bisphenol A in aerobic denitrifying cultures and its coercive mechanism on the nitrogen transformation pathway.

Bisphenol A (BPA) is a commonly used endocrine-disrupting chemical found in high levels in wastewater worldwide. Aerobic denitrification is a promising alternative to conventional nitrogen removal processes. However, the effects of BPA on this novel nitrogen removal process have rarely been reported. Herein, we investigated the removal and interaction effects of BPA (0, 0.1, 1, and 10 mg/L) in aerobic denitrifying cultures. Our experimental results demonstrated that the aerobic denitrification system could remove 66%-86% of BPA from wastewater. Fourier transform infrared spectroscopy revealed that polysaccharides and amides were the primary sites for adsorption. An increase in the type and number of intermolecular hydrogen bonds might enhance the ability of aerobic denitrifying cultures to adsorb BPA. Adsorption kinetics analysis demonstrated that inhomogeneous multilayer adsorption was the leading cause of BPA removal. Adsorbed BPA decreased the sedimentation, flocculation, and hydrophobicity of aerobic denitrifying cultures, triggering changes in the levels of proteins and polysaccharides in extracellular polymeric substances. As the influent BPA increased from 0 to 10 mg/L, the nitrate-nitrogen and total organic carbon in the reactor effluent increased from 0.4 ± 0.2 and 26 ± 7.9 mg/L to 18.8 ± 9.3 and 116.2 ± 55.6 mg/L, respectively. BPA (initial concentration range: 1-10 mg/L) significantly influenced the abundance of genes involved in the nitrogen transformation pathway, contributing to the increase in the abundance of gaseous NOx-transformed genes and altering the relative abundance of denitrifying bacteria, particularly Thauera. Correlation analyses revealed that Pseudomonas, Thauera, and AKYH767 are important for maintaining systemic nitrogen transformations and BPA adsorption.

Exploring the role of Bisphenol A in obesity-driven colorectal cancer progression: network toxicology and multi-organ pathology in animal models.

Bisphenol A (BPA), an endocrine disruptor, is linked to cancer progression in estrogen-responsive tissues, but its role in promoting colorectal cancer (CRC) progression in the context of obesity remains underexplored. This study examines BPA's influence on CRC in obese Sprague-Dawley rats using network toxicology and experimental models. Computational analysis using the Database for Annotation, Visualization, and Integrated Discovery identified pathways such as "CRC" and "chemical carcinogenesis-receptor activation", implicating the PI3K-AKT pathway in IL-1 beta upregulation and BPA's role in CRC during obesity. Thirty male rats were grouped (n = 6) as follows: N (normal diet), NC (normal diet + CRC), HC (high-fat diet + CRC), NCB (normal diet + CRC + BPA), and HCB (high-fat diet + CRC + BPA). CRC was induced with 1,2-dimethylhydrazine (40 mg/kg), and BPA (25 mg/kg) was administered for 19 weeks. Although BPA exposure did not affect body weight or biochemical parameters, the HCB group exhibited significant histopathological changes in the colon, including lymphoid hyperplasia, liver damage, and increased IL-1β levels. Furthermore, diet influenced adipocyte size, exacerbating BPA's effects on CRC progression. Findings suggest BPA may worsen CRC progression in obese rats through identified pathways, promoting multi-organ pathology and underscoring the need for stricter regulations, especially for vulnerable populations. ENVIRONMENTAL IMPLICATION: Bisphenol A (BPA), a widespread environmental contaminant, is increasingly linked to serious health issues, including cancer, in susceptible populations. Our study highlights BPA's role in promoting obesity-driven colorectal cancer (CRC) progression, demonstrating its carcinogenic potential in high-risk contexts. These findings emphasize the urgent need for regulatory scrutiny of BPA exposure, particularly in obese individuals, and support the development of safer alternatives. Addressing BPA's impact can contribute to preventive health strategies and inform policies aimed at reducing environmental and public health risks associated with endocrine-disrupting chemicals.

BPA and low-Se exacerbate apoptosis and mitophagy in chicken pancreatic cells by regulating the PTEN/PI3K/AKT/mTOR pathway

IntroductionBisphenol A (BPA) is a widespread environmental pollutant which has serious toxic effects on organisms. One of the crucial trace elements is selenium (Se), whose shortage can harm biological tissues and enhance the toxicity of contaminants, in which apoptosis and autophagy are core events. ObjectivesAn in vivo model was established to investigate the effects of BPA and low-Se on chicken pancreatic tissue, and identify the possible potential molecular mechanism. MethodsA total of 80 1-day-old broiler chickens (Xinghua Chicken Farm, Harbin, China) were stochastically divided into 4 groups (n=20/group): Control group, BPA group, low-Se group, and low-Se + BPA group. Pancreatic tissue was collected at day 42 to detect changes in markers. ResultsFirst, the data showed that BPA and low-Se exposure gave rose to structural abnormalities in pancreatic tissue, oxidative stress, mitochondrial dysfunction and homeostasis imbalance, apoptosis and mitophagy. In addition, the co-exposure of BPA and low-Se caused the most serious damage to pancreatic tissue. In terms of mechanism, it was found that apoptosis and mitophagy induced by BPA and low-Se were related to the activation of PTEN/PI3K/AKT/mTOR pathway. ConclusionIn summary, the study found that BPA and low-Se exacerbated mitochondria damage, apoptosis and mitophagy by regulating the PTEN/PI3K/AKT/mTOR pathway.

A comprehensive review on advanced trends in treatment technologies for removal of Bisphenol A from aquatic media.

Toxic environmental pollutants are considered to be posed a major threat to human and aquatic systems. The fast advancement of the petrochemical and chemical industries has woken up rising worries concerning the pollution of water by contaminants including phenolic Bisphenol A (BPA), an endocrine-disrupting chemical (EDC). The intermediate BPA used in synthesis of certain plastics, polycarbonate polymers, polysulfone, and epoxy resins of various polyesters. Due to potential health risks, severe toxicity, and widespread distribution, there is an urgent need to develop efficient techniques for the removal of BPA. Therefore, advance management for the active elimination of BPA prior to its release into the water sources is of serious concern. Degradation, membrane separation, adsorption, and biological treatments have been extensively examined as they are easy to operate and cost-effective for effective BPA removal. In this review, we summarized the mechanism and performance for removal of BPA by several sorbents, including natural polymers, natural inorganic minerals, porous and carbon-based materials. Comparative results revealed that composite materials and modified adsorbents have good performances for removal of BPA. Furthermore, kinetic study investigating adsorption mechanisms was also discussed. Hazardous quantities of such types of chemicals in various samples have thus been the subject of increasing concern of investigation. This review clarified the extensive literature regarding the major health effects of BPA and its advanced treatment technologies including biological treatment by natural and synthetic materials have been discussed briefly. It delivers regulation for future development and research from the aspects of materials functionalization, development of methods, and mechanism investigation that directing to stimulate developments for removal of emerging contaminants.

Effect of Bisphenol F on Reproductive Function in F1 Generation Male Mice and its Potential Mechanisms.

Bisphenol F (BPF) is an environmental endocrine disruptor capable of crossing the placental barrier and affecting the growth and development of offspring. Despite its potential impact, systematic research about effects of BPF on the reproductive function of male offspring remains limited. In this study, pregnant female mice were exposed to BPF at doses of 40, 400, and 4000 μg/kg during gestation and lactation, respectively, to evaluate its impact on testicular damage, testosterone levels, and spermatogenesis of male offspring (F1 generation), and further explore the mechanisms using transcriptomics. First, the study demonstrated that BPF induces testicular damage in F1 generation mice, leading to decreased testosterone levels and sperm quality. Second, transcriptomic analysis revealed that BPF affected spermatogenesis in F1 generation mice by disrupting retinol metabolism. Third, transcriptomic analysis revealed that BPF reduce the capacity for testosterone synthesis in F1 generation mice by diverting the testosterone precursor dehydroepiandrosterone (DHEA) towards the synthesis of 16α-hydroxydehydroepiandrosterone rather than testosterone. Finally, it was confirmed that BPF hinder cholesterol transport to mitochondria by inhibiting the cAMP signaling pathway, thereby impacting testosterone synthesis. In summary, the results of this study suggest that gestational exposure to BPF can lead to reproductive dysfunction in F1 generation male mice.

The Effects of Bisphenol A of Polycarbonate Plastics on Various Blood and Fertility Parameters, along with Histological Changes in Male Albino Rats

The Effects of Bisphenol A of Polycarbonate Plastics on Various Blood and Fertility Parameters, along with Histological Changes in Male Albino Rats

The Effect of Bisphenol and Its Cytotoxicity on Female Infertility and Pregnancy Outcomes: A Narrative Review

The Effect of Bisphenol and Its Cytotoxicity on Female Infertility and Pregnancy Outcomes: A Narrative Review

Maternal bisphenol A (BPA) exposure induces placental dysfunction and health risk in adult female offspring: Insights from a mouse model

Bisphenol A (BPA) is an endocrine disruptor that poses multiple risks to human health. In particular, the potential adverse effects of maternal exposure to BPA on offspring warrant further investigation. In this study, pregnant mice were exposed to BPA throughout gestation and the effects of BPA on placental function, fetal development, and health risks in adult offspring were assessed. The results showed that exposure to BPA during pregnancy led to abnormal fetal weight during the mid-to-late stages. Positron emission tomography (PET)/computed tomography (CT) and quantitative polymerase chain reaction (qPCR) were used to assess the expression of glucose transporters. The results showed that maternal BPA exposure altered glucose transport by upregulating Glut1. This alteration may significantly affect placental function and fetal development. Placental metabolomic analysis showed that BPA exposure led to downregulation of key intermediates in glucose metabolism, including UDP-d-glucose and D-glucosamine-6-phosphate. Additionally, the glycerophospholipid metabolite Dipalmitoylphosphatidylcholine (DPPC) was upregulated while CDP-choline and CDP-ethanolamine were downregulated. These disturbances in placental energy metabolism and alterations in glucose transport may be related to decreased fasting blood glucose levels and abnormal glucose tolerance in female offspring; however, these indices remained unaltered in male offspring. These findings provide preliminary insights into the potential pathological mechanisms underlying placental dysfunction and health risk caused by maternal BPA exposure in adult female offspring.

Bisphenol A and its potential mechanism of action for reproductive toxicity.

Bisphenol A (BPA) is an organic synthetic chemical used worldwide. Billions of pounds of BPA are produced annually through industrial processes to be used in commercial products, making human exposure to BPA ubiquitous. Concerns have been raised due to the potential adverse health effects of BPA, specifically in vulnerable populations, such as pregnant persons and children. BPA is an endocrine-disrupting chemical, and through this function has been linked to reproductive toxicity. We review BPA's historical and current use, health and safety concerns and regulations, sources of exposure, and evidence for male and female reproductive toxicity. Evidence from epidemiological and animal studies idenfity that low- and high-exposure levels of BPA (prenatal, postnatal and adulthood exposure) can adversely affect male and female fertility and reproductive organs. While the cause of BPA-induced reproductive toxicity is not fully understood, we discuss BPA's estrogenic and androgenic activity, and its ability to disrupt the hypothalamic-pituitary-gonadal axis as a potential associated mechanism. There are significant differences in tolerable daily intakes of BPA set by global agencies, making interpretation of previous and emerging research findings challenging and inconsistent. Although BPA is deemed toxic by some government agencies, most do not currently consider it a health risk due to low populational exposure levels. However, we highlight evidence that even at acute, low exposure, BPA can adversely affect reproductive function. We recommend continuing research into the adverse effects of BPA on human health and revisiting the regulatory measures of BPA to limit exposure and promote public awareness of its potential to cause reproductive toxicity.

Comparative study of cytotoxic Signaling pathways in H1299 cells exposed to alternative Bisphenols: BPA, BPF, and BPS.

Bisphenols are prevalent in food, plastics, consumer goods, and industrial products. Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and bisphenol S (BPS), are known to act as estrogen mimics, leading to reproductive disorders, disruptions in fat metabolism, and abnormalities in brain development. Despite numerous studies exploring the adverse effects of bisphenols both in vitro and in vivo, the molecular mechanisms by which these compounds affect lung cells remain poorly understood. This study aims to compare the effects of BPA, BPF, and BPS on the physiological behavior of human nonsmall cell lung cancer (NSCLC) cells. Human non-small cell lung cancer (NSCLC) H1299 cells were treated with various concentration of BPA, BPF and BPS during different exposure time. Cellular physiology for viability and cell cycle was assessed by the staining with apoptotic cell makers such as active Caspase-3 and cyclins antibodies. Toxicological effect was quantitatively counted by using flow-cytometry analysis. Our findings indicate that BPA induces apoptosis by increasing active Caspase-3 levels in H1299 cells, whereas BPF and BPS do not promote late apoptosis. Additionally, BPA was found to upregulate cyclin B1, causing cell cycle arrest at the G0/G1 phase and leading to apoptotic cell death through Caspase-3 activation. Conclusion: These results demonstrate that BPA, BPF, and BPS differentially impact cell viability, cell cycle progression, and cell death in human NSCLC cells.

Bisphenol A and Its Emergent Substitutes: State of the Art of the Impact of These Plasticizers on Oxidative Stress and Its Role in Vascular Dysfunction.

The "One Health approach" has evidenced the significant impact of xenobiotic exposure to health, and humans are a relevant target for their toxic effects. Bisphenol A (BPA) exerts a ubiquitous exposure source in all ecosystems. Given its endocrine-disrupting and harmful consequences on health, several countries have enforced new regulations to reduce exposure to BPA. Cardiovascular diseases (CVDs) are complex conditions that lead to higher mortality worldwide, where family history, lifestyle, and environmental factors, like BPA exposure, have a remarkable contribution. This chemical compound is the most widely used in plastic and epoxy resin manufacturing and has been associated with effects on human health. Therefore, new-generation bisphenols (NGBs) are replacing BPA use, arguing that they do not harm health. Nonetheless, the knowledge about whether NGBs are secure options is scanty. Although BPA's effects on several organs and systems have been documented, the role of BPA and NGBs in CVDs has yet to be explored. This review's goals are focused on the processes of endothelial activation (EA)-endothelial dysfunction (ED), a cornerstone of CVDs development, bisphenols' (BPs) effects on these processes through oxidant and antioxidant system alteration. Despite the scarce evidence on pro-oxidant effects associated with NGBs, our review demonstrated a comparable harmful effect on BPA. The results from the present review suggest that the biological mechanisms to explain BPs cardiotoxic effects are the oxidant stress ↔ inflammatory response ↔ EA ↔ ED → atherosclerotic plate → coagulation promotion. Other effects contributing to CVD development include altered lipid metabolism, ionic channels, and the activation of different intracellular pathways, which contribute to ED perpetuation in a concerted manner.

MicroRNA-34a-5p regulates agouti-related peptide via krüppel-like factor 4 and is disrupted by bisphenol A in hypothalamic neurons

Obesity is a complex disease marked by increased adiposity and impaired metabolic function. While diet and lifestyle are primary causes, endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), significantly contribute to obesity. BPA, found in plastic consumer products, accumulates in the hypothalamus and dysregulates energy homeostasis by disrupting the neuropeptide Y (NPY)/agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) neurons.However, the precise molecular mechanisms of how BPA disrupts neuropeptide expression remains unclear. We hypothesized that microRNAs (miRNAs), which regulate approximately 60% of the human protein-coding genome and are crucial for hypothalamic energy regulation, may mediate the effects of BPA on Agrp. Using the TargetScanMouse 8.0 and DIANA microT bioinformatics tools, we identified miR-501-5p as a potential miRNA that directly regulates Agrp and the miR-34 family as miRNAs that indirectly regulate Agrp through its transcription factor krüppel-like factor 4 (KLF4). We found that in an immortalized NPY/AgRP-expressing cell line, mHypoE-41, miR-501-5p unexpectedly upregulated Agrp, while miR-34a-5p reduced Klf4 and Agrp mRNA levels. Serum starvation reduced miR-34a-5p levels and elevated Agrp mRNA levels, suggesting a potential role in AgRP regulation. Inhibiting the miR-34a-5p interaction with the Klf4 3′UTR using a specific target site blocker prevented the downregulation of both Klf4 and Agrp, suggesting miR-34a-5p alters Agrp mRNA levels via regulation of KLF4. BPA treatment increased Agrp and Klf4 expression while simultaneously decreasing miR-34a-5p levels, indicating miR-34a-5p may play a role in BPA-mediated dysregulation of Agrp. Overall, this study highlights indirect miRNA-based regulation of Agrp, which can also be dysregulated by obesogens, such as BPA.

Bisphenol A impairs oocyte maturation by dysfunction of cumulus cells

Bisphenol A (BPA) is a well-known environmental endocrine disruptor that has detrimental effects on reproduction. This study aimed to investigate whether BPA exposure could disrupt the function of cumulus cells and influence oocyte maturation and development. Porcine oocytes at the germinal vesicle stage were exposed to BPA for 44 h. The results revealed that BPA exposure led to dysfunction in cumulus cells by inhibiting meiotic division, inducing endoplasmic reticulum stress, and disrupting steroid synthesis. Furthermore, BPA exposure significantly increased reactive oxygen species and caused abnormal distribution of mitochondria in the oocytes. Notably, matured oocytes in the MII stage from the BPA-exposed groups showed significantly reduced development to the blastocyst stage, along with increased autophagy and apoptosis. These findings suggest that cumulus-oocyte complexes are sensitive to BPA exposure during the germinal vesicle stage, and the toxic effects of BPA on cumulus cells can severely inhibit oocyte and parthenogenetic embryos development.

Short-Term Exposure of Bisphenol A Deteriorates the Quality of Rabbit Milk by Impairing Milk Fat Synthesis.

This study aimed to investigate the effects of short-term exposure of Bisphenol A (BPA) on the growth and lactation performance, blood parameters, and milk composition of lactating rabbits and explore its potential molecular mechanisms. Eight lactating rabbits with similar body weight were selected and randomly divided into the experimental group (BPA) and the control group (Ctrl). The group BPA was orally administered 80 mg/kg/day BPA on the 15th day postpartum, while the group Ctrl received a corresponding volume of vehicle. Blood and milk samples were collected after 7 days treatment. The results showed that short-term ingestion of BPA did not obviously alter the body weight, feed intake, or milk yield of the lactating rabbits. ELISA assays indicated that BPA did not significantly affect the plasma levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), creatinine (CRE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), and urea. Utilizing untargeted metabolomics, we first depicted the metabolomic profile of rabbit milk, and identified 277 differential metabolites (DMs), with 141 DMs upregulated (e.g., BPA, and its metabolites including Cetirizine N-oxide) and 136 DMs downregulated (e.g., Oleamide, Tiglic acid, PC O-38:4) in the group BPA. KEGG analysis revealed that the DMs were mainly enriched in pathways comprising fatty acid metabolism, fatty acid degradation, and phosphatidylinositol signaling system, emphasizing the effect of BPA on milk fat metabolism. Hence, we established the BPA-induced MAC-T model, and the results showed that BPA significantly reduced cell viability and impacted lipid synthesis, as evidenced by reduced lipid droplets (BODIPY and Oil Red O staining) and decreased expression of genes related to lipid synthesis (e.g., PPARγ, ACACA, LPL). In summary, we first drew the metabolomic profile of rabbit milk and confirmed that short-term BPA exposure impacted mammary lipid synthesis, thereby reducing the milk quality of lactating rabbits and providing fundamental data for resolving the toxicological mechanisms of BPA on mammal lactation.

Bisphenol A and its metabolites promote white adipogenesis and impair brown adipogenesis in vitro

Bisphenol A (BPA), an obesogen, can disrupt adipogenesis in vitro, but these studies did not distinguish adipocytes as white or brown. BPA can be metabolized into BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). These metabolites are not completely inactive in the body, but the related studies remain limited. In this study, preadipocytes isolated from mouse white and brown adipose tissues were treated with 0.1, 1, and 10 μM of BPA and its metabolites for 6 days, which are equivalent to the exposure level of general and occupational populations, to investigate and compare the effects of BPA and its metabolites on white and brown adipogenesis. The results showed that BPA and BPA-G increased lipid accumulation during white adipogenesis, whereas only BPA induced this same effect during brown adipogenesis. Moreover, BPA and its metabolites upregulated the expression of pan-adipogenic markers, such as peroxisome proliferator-activated receptor gamma (PPARγ), during white adipogenesis, whereas they downregulated that of PPARγ during brown adipogenesis. Additionally, BPA also inhibited the mRNA and protein expression of brown fat-specific markers (e.g., PPARγ coactivator 1–1alpha (PGC1-α) and uncoupling protein 1 (UCP1)), and mitochondrial activity during brown adipogenesis, and BPA-G also reduced the mRNA expression levels of Pgc1-α and Ucp1. These findings indicated that BPA induced different effects on white and brown adipogenesis, enhancing the former and hindering the latter. Despite less potent than BPA, BPA-G and BPA-S might also affect white and brown adipogenesis. This research provides in-depth insights into the obesogenic effects of BPA and the biological activities of its metabolites.

Bisphenol A disrupts the neuronal F-actin cytoskeleton by activating the RhoA/ROCK/LIMK pathway in Neuro-2a cells

Bisphenol A (BPA) is an environmental endocrine disruptor that is widely present in the environment and has been reported to affect neuronal cytoskeleton and neural function. However, the exact molecular mechanisms remain unclear. In the present study, the effects of BPA on cytoskeleton rearrangement were examined, and the associated signaling pathways, which were influenced by the RhoA/ROCK/LIMK pathway in Neuro-2a cells in vitro, were identified. Specifically, Neuro-2a cells were exposed to BPA, and the effects of BPA exposure on the cytoskeleton of neuronal cells and on the activation or nonactivation of the RhoA/ROCK signaling pathway were evaluated using Cell Counting Kit-8 (CCK8), phalloidin staining, western blot, and real-time PCR. A RhoA inhibitor (Rhosin hydrochloride) and a ROCK inhibitor (Y-27632) were then used to elucidate the precise function of the pathway. The results demonstrated that 50–100 μM BPA exposure inhibited Neuro-2a cell viability and caused the formation of aberrantly polymerized F-actin and stress fibers. In addition, the RhoA/ROCK pathway was activated, and the expression levels of the pathway-related molecules—RhoA, ROCK2, LIMK1, Cofilin, Profilin, p-MLC2, and F-actin were dramatically elevated. The addition of Rhosin and Y-27632 resulted in a decrease in F-actin polymerization in the Neuro-2a cells, the disassembly of stress fibers, and a noteworthy drop in the levels of molecular proteins related to the RhoA/ROCK pathway affected by BPA. Together, these new findings indicated that BPA exposure thus activated the RhoA/ROCK signaling pathway and caused an abnormal accumulation of F-actin in the Neuro-2a cells, in turn altering the microfilament cytoskeleton. F-actin was restored when the RhoA/ROCK pathway was inhibited, suggesting that the process of BPA-induced neuronal cytoskeletal degradation is linked to the RhoA/ROCK signaling cascade.

The Effects of Bisphenol A and its Analogs on Steroidogenesis in MA-10 Leydig Cells and KGN Granulosa Cells†.

Bisphenols are a family of chemicals used in the manufacture of consumer products containing polycarbonate plastics and epoxy resins. Studies have shown that exposure to bisphenol A (BPA) may disrupt steroidogenesis and induce adverse effects on male and female reproduction, but little is known about BPA replacements. We determined the effects of six bisphenols on the steroidogenic function of MA-10 Leydig cells and KGN granulosa cells by measuring the levels of progesterone and estradiol produced by these cells as well as the expression of transcripts involved in steroid and cholesterol biosynthesis. MA-10 and KGN cells were exposed for 48hours to one of six bisphenols (0.01-50μM): BPA, bisphenol F, bisphenol S, bisphenol AF, bisphenol M, or bisphenol TMC under both basal and dibutyryl cAMP (Bu2cAMP)-stimulated conditions. In MA-10 cells, most bisphenols increased the Bu2cAMP-stimulated production of progesterone. In KGN cells, there was a general decrease in progesterone production, while estradiol levels were increased following exposure to many bisphenols. qRT-PCR analyses revealed that all six bisphenols (≥1μM) upregulated the expression of STAR, a cholesterol transporter, in both cell lines after stimulation. Key transcripts directly involved in steroid and cholesterol biosynthesis were significantly altered in a cell line, chemical, and concentration-dependent manner. The expression of upstream genes was also differentially affected. Thus, BPA and five of its analogs can disrupt steroid production in two steroidogenic cell lines and alter the levels of transcripts involved in this process. Importantly, BPA replacements do not appear to have fewer effects than BPA.