Bisphenol A (BPA) Leading to Obesity and Cardiovascular Complications: A Compilation of Current In Vivo Study

BPA is one of the most common endocrine disruptors that is widely being manufactured daily nationwide. Although scientific evidence supports claims of negative effects of BPA on humans, there is also evidence suggesting that a low level of BPA is safe. However, numerous in vivo trials contraindicate with this claim and there is a high possibility of BPA exposure could lead to obesity. It has been speculated that this does not stop with the exposed subjects only, but may also cause transgenerational effects. Direct disruption of endocrine regulation, neuroimmune and signaling pathways, as well as gut microbiata, has been identified to be interrupted by BPA exposure, leading to overweight or obesity. In these instances, cardiovascular complications are one of the primary notable clinical signs. In regard to this claim, this review paper discusses the role of BPA on obesity in the perspective of endocrine disruptions and possible cardiovascular complications that may arise due to BPA. Thus, the aim of this review is to outline the changes in gut microbiota and neuroimmune or signaling mechanisms involved in obesity in relation to BPA. To identify potentially relevant articles, a depth search was done on the databases Nature, PubMed, Wiley Online Library, and Medline & Ovid from the past 5 years. According to Boolean operator guideline, selected keywords such as (1) BPA OR environmental chemical AND fat OR LDL OR obese AND transgenerational effects or phenocopy (2) Endocrine disruptors OR chemical AND lipodystrophy AND phenocopy (3) Lipid profile OR weight changes AND cardiovascular effect (4) BPA AND neuroimmune OR gene signaling, were used as search terms. Upon screening, 11 articles were finalized to be further reviewed and data extraction tables containing information on (1) the type of animal model (2) duration and dosage of BPA exposure (3) changes in the lipid profile or weight (4) genes, signaling mechanism, or any neuroimmune signal involved, and (5) transgenerational effects were created. In toto, the study indicates there are high chances of BPA exposure affecting lipid profile and gene associated with lipolysis, leading to obesity. Therefore, this scoping review recapitulates the possible effects of BPA that may lead to obesity with the evidence of current in vivo trials. The biomarkers, safety concerns, recommended dosage, and the impact of COVID-19 on BPA are also briefly described.     

食品及包装材料中烷基酚及双酚A的检测方法

烷基酚和双酚A是典型的内分泌干扰物,能对人的生殖发育、内分泌系统造成危害,为提高食品安全性,对食品及包装材料中烷基酚和双酚A的检测显得尤为重要,本文对烷基酚和双酚A的检测技术进行综述。     

含双酚A的废水处理

环境内分泌干扰物对人类生存的环境和身心健康产生了严重的影响,造成了一定程度的危害,双酚A(Bisphenol A,BPA)是其中重要的一种。随着双酚A的大量使用,在世界各地各种水体中都有发现,因此对双酚A污染的治理势在必行。通过了解和分析双酚A的性质、用途、使用范围等方面的知识,主要研究含双酚A废水的处理方法和技术,从多角度多方面研究含双酚A的废水处理,希望可以帮助缓解含双酚A废水所带来的环境污染问题。     

Preparation of porous polysulfone beads for selective removal of endocrine disruptors

Porous polysulfone (PSf) beads are prepared using a liquid–liquid phase separation technique. The porous PSf beads are then used for the removal of endocrine disruptors, such as Biphenyl (BP), dibenzofuran (DBF), dibenzo-p-dioxin (DBD), biphenol A (BPA), and diethylstylbestrol (DES) from their aqueous solutions. The endocrine disruptors could be removed efficiently by a simple sorption method with hydrophobic porous PSf beads. The removal ratio was high for endocrine disruptors having high octanol–water distribution coefficients. The effect of sorption time, weight of PSf beads, ethanol amount in the solution, and the porosity of the beads on the removal of endocrine disruptors was investigated. The adsorbed endocrine disruptors in the PSf beads could be effectively removed by 2-propanol or ethanol, which indicated that the beads could be reused. The study suggested that the porous PSf beads have a potential ability to be used for the removal of endocrine disruptors in environmental application.     

SPE-GC/MS法快速检测水体中多组分内分泌干扰物

采用固相萃取-气相色谱/质谱法(SPE-GC/MS)研究了温州8个水体中邻苯二甲酸二甲酯、西玛津、莠去津、甲草胺、邻苯二甲酸二丁酯、双酚A、邻苯二甲酸二(2-乙基己基)酯七种内分泌干扰物的残留。水样用C18柱固相萃取进行富集、3mL10%的甲醇水溶液淋洗、10mL丙酮洗脱;并采用GC-MS法对七种内分泌干扰素进行分析。本实验建立的方法定性定量准确、可靠,适用于水体中多组分内分泌干扰物的快速检测,在所有测定的水样中,邻苯二甲酸二丁酯、双酚A、邻苯二甲酸二(2-乙基己基)酯是主要残留物,最高残留邻苯二甲酸二丁酯、双酚A、邻苯二甲酸二(2-乙基己基)酯分别为0.82、3.16、1.50ng/L。     

Non-isothermal bioreactors in enzymatic remediation of waters polluted by endocrine disruptors: BPA as a model of pollutant

The bioremediation of waters polluted by Bisphenol A, taken as a model for endocrine disruptors, has been pursued by means of catalytic membranes in bioreactors operating under isothermal and non-isothermal conditions. Laccase from Trametes versicolor was immobilized on nylon membranes grafted with Glycidyl Methacrylate and using Phenylendiamine as spacer. The behaviour of the catalytic membrane was studied as a function of BPA concentration. Affinities of immobilized laccase towards BPA were found to increase with average temperature and under non-isothermal conditions. Percentage increases of enzyme activity, proportional to the applied temperature differences, were found to decrease with the increase of BPA concentrations. Interestingly, the highest levels of BPA biodegradation occurred at the lowest concentrations, in other words those present in wastewaters given the small water solubility of this compound. The results are discussed in terms of the process of thermodialysis by considering the additional BPA fluxes towards the immobilized enzymes driven by the temperature gradients.     

Epigenetic Inheritance: Intergenerational Effects of Pesticides and Other Endocrine Disruptors on Cancer Development

Parental environmental experiences affect disease susceptibility in the progeny through epigenetic inheritance. Pesticides are substances or mixtures of chemicals—some of which are persistent environmental pollutants—that are used to control pests. This review explores the evidence linking parental exposure to pesticides and endocrine disruptors to intergenerational and transgenerational susceptibility of cancer in population studies and animal models. We also discuss the impact of pesticides and other endocrine disruptors on the germline epigenome as well as the emerging evidence for how epigenetic information is transmitted between generations. Finally, we discuss the importance of this mode of inheritance in the context of cancer prevention and the challenges ahead.     

Sex-Specific Effects of Plastic Caging in Murine Viral Myocarditis

Background: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. Methods: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. Results: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. Conclusions: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.     

Influence of Risk Factors for Male Infertility on Sperm Protein Composition

Male infertility is a common health problem that can be influenced by a host of lifestyle risk factors such as environment, nutrition, smoking, stress, and endocrine disruptors. These effects have been largely demonstrated on sperm parameters (e.g., motility, numeration, vitality, DNA integrity). In addition, several studies showed the deregulation of sperm proteins in relation to some of these factors. This review inventories the literature related to the identification of sperm proteins showing abundance variations in response to the four risk factors for male infertility that are the most investigated in this context: obesity, diabetes, tobacco smoking, and exposure to bisphenol-A (BPA). First, we provide an overview of the techniques used to identify deregulated proteins. Then, we summarise the main results obtained in the different studies and provide a compiled list of deregulated proteins in relation to each risk factor. Gene ontology analysis of these deregulated proteins shows that oxidative stress and immune and inflammatory responses are common mechanisms involved in sperm alterations encountered in relation to the risk factors.     

Are BPA Substitutes as Obesogenic as BPA?

Metabolic diseases, such as obesity, Type II diabetes and hepatic steatosis, are a significant public health concern affecting more than half a billion people worldwide. The prevalence of these diseases is constantly increasing in developed countries, affecting all age groups. The pathogenesis of metabolic diseases is complex and multifactorial. Inducer factors can either be genetic or linked to a sedentary lifestyle and/or consumption of high-fat and sugar diets. In 2002, a new concept of “environmental obesogens” emerged, suggesting that environmental chemicals could play an active role in the etiology of obesity. Bisphenol A (BPA), a xenoestrogen widely used in the plastic food packaging industry has been shown to affect many physiological functions and has been linked to reproductive, endocrine and metabolic disorders and cancer. Therefore, the widespread use of BPA during the last 30 years could have contributed to the increased incidence of metabolic diseases. BPA was banned in baby bottles in Canada in 2008 and in all food-oriented packaging in France from 1 January 2015. Since the BPA ban, substitutes with a similar structure and properties have been used by industrials even though their toxic potential is unknown. Bisphenol S has mainly replaced BPA in consumer products as reflected by the almost ubiquitous human exposure to this contaminant. This review focuses on the metabolic effects and targets of BPA and recent data, which suggest comparable effects of the structural analogs used as substitutes.     

FTO m6A Demethylase in Obesity and Cancer: Implications and Underlying Molecular Mechanisms

Fat mass and obesity-associated protein (FTO) is the first reported RNA N6-methyladenosine (m6A) demethylase in eukaryotic cells. m6A is considered as the most abundant mRNA internal modification, which modulates several cellular processes including alternative splicing, stability, and expression. Genome-wide association studies (GWAS) identified single-nucleotide polymorphisms (SNPs) within FTO to be associated with obesity, as well as cancer including endometrial cancer, breast cancer, pancreatic cancer, and melanoma. Since the initial classification of FTO as an m6A demethylase, various studies started to unravel a connection between FTO’s demethylase activity and the susceptibility to obesity on the molecular level. FTO was found to facilitate adipogenesis, by regulating adipogenic pathways and inducing pre-adipocyte differentiation. FTO has also been investigated in tumorigenesis, where emerging studies suggest m6A and FTO levels are dysregulated in various cancers, including acute myeloid leukemia (AML), glioblastoma, cervical squamous cell carcinoma (CSCC), breast cancer, and melanoma. Here we review the molecular bases of m6A in tumorigenesis and adipogenesis while highlighting the controversial role of FTO in obesity. We provide recent findings confirming FTO’s causative link to obesity and discuss novel approaches using RNA demethylase inhibitors as targeted oncotherapies. Our review aims to confirm m6A demethylation as a risk factor in obesity and provoke new research in FTO and human disorders.     

Unexpected Interacting Effects of Physical (Radiation) and Chemical (Bisphenol A) Treatments on Male Reproductive Functions in Mice

For decades, numerous chemical pollutants have been described to interfere with endogenous hormone metabolism/signaling altering reproductive functions. Among these endocrine disrupting substances, Bisphenol A (BPA), a widely used compound, is known to negatively impact germ and somatic cells in the testis. Physical agents, such as ionizing radiation, were also described to perturb spermatogenesis. Despite the fact that we are constantly exposed to numerous environmental chemical and physical compounds, very few studies explore the impact of combined exposure to chemical and physical pollutants on reproductive health. The aim of this study was to describe the impact of fetal co-exposure to BPA and IR on testicular function in mice. We exposed pregnant mice to 10 µM BPA (corresponding to 0.5 mg/kg/day) in drinking water from 10.5 dpc until birth, and we irradiated mice with 0.2 Gy (γ-ray, RAD) at 12.5 days post-conception. Co-exposure to BPA and γ-ray induces DNA damage in fetal germ cells in an additive manner, leading to a long-lasting decrease in germ cell abundance. We also observed significant alteration of adult steroidogenesis by RAD exposure independently of the BPA exposure. This is illustrated by the downregulation of steroidogenic genes and the decrease of the number of adult Leydig cells. As a consequence, courtship behavior is modified, and male ultrasonic vocalizations associated with courtship decreased. In conclusion, this study provides evidence for the importance of broadening the concept of endocrine disruptors to include physical agents, leading to a reevaluation of risk management and regulatory decisions.     

The Endocrine Disruptor Compound Bisphenol-A (BPA) Regulates the Intra-Tumoral Immune Microenvironment and Increases Lung Metastasis in an Experimental Model of Breast Cancer

Simple SummaryThe widely spread microplastic component and endocrine disruptor BPA is a hazardous material recognized for a long time. Here, for the first time, we demonstrated that BPA, administered into mice in a very specific developmental step of the animal (3 days post-natal), induces an increase in metastasis to the lung in the adult life, compared to the control or vehicle mice. In addition, of novelty, it is the analysis of the cytokine tumor microenvironment, which is the reason for the increased metastasis by BPA (BPA induce the increase in pro-metastatic cytokines).AbstractBreast cancer (BC) metastasis represents the main physiopathology leading to poor prognosis and death. Bisphenol A (BPA) is a pollutant, classified as an endocrine-disrupting chemical compound with estrogenic properties, their exposure in the early stages of neonatal life leads to an increase in the size and weight of breast tumors and induces cellular changes in the tumoral immune microenvironment where cytokines play a key role. Thus, we used female BALB/c mice exposed neonatally to a single dose of BPA. Once mice reached sexual maturity, a mammary tumor was induced, injecting 4T1 cells in situ. After 25 days of injection, we evaluated endocrine alterations, cytokine expression, tissue alterations denoted by macro or micro-metastasis in the lung, and cell infiltration induced by metastasis. We found that BPA neonatal treatment did not show significant endocrine alterations. Noteworthy, BPA led to an augmented rate of metastasis to the lung associated with higher intratumoral expression of IL-1β, IL-6, IFN-γ, TNF-α, and VEGF. Our data suggest that cytokines are key players in the induction of BC metastasis and that BPA (an environmental pollutant) should be considered as a risk factor in the clinical history of patients as a possible inductor of BC metastasis.     

Nutrient Sensing via Gut in Drosophila melanogaster

Nutrient-sensing mechanisms in animals’ sense available nutrients to generate a physiological regulatory response involving absorption, digestion, and regulation of food intake and to maintain glucose and energy homeostasis. During nutrient sensing via the gastrointestinal tract, nutrients interact with receptors on the enteroendocrine cells in the gut, which in return respond by secreting various hormones. Sensing of nutrients by the gut plays a critical role in transmitting food-related signals to the brain and other tissues informing the composition of ingested food to digestive processes. These signals modulate feeding behaviors, food intake, metabolism, insulin secretion, and energy balance. The increasing significance of fly genetics with the availability of a vast toolbox for studying physiological function, expression of chemosensory receptors, and monitoring the gene expression in specific cells of the intestine makes the fly gut the most useful tissue for studying the nutrient-sensing mechanisms. In this review, we emphasize on the role of Drosophila gut in nutrient-sensing to maintain metabolic homeostasis and gut-brain cross talk using endocrine and neuronal signaling pathways stimulated by internal state or the consumption of various dietary nutrients. Overall, this review will be useful in understanding the post-ingestive nutrient-sensing mechanisms having a physiological and pathological impact on health and diseases.     

The GRKs Reactome: Role in Cell Biology and Pathology

G protein-coupled receptor kinases (GRKs) are protein kinases that function in concert with arrestins in the regulation of a diverse class of G protein-coupled receptors (GPCRs) signaling. Although GRKs and arrestins are key participants in the regulation of GPCR cascades, the complex regulatory mechanisms of GRK expression, its alternation, and their function are not thoroughly understood. Several studies together with the work from our lab in recent years have revealed the critical role of these kinases in various physiological and pathophysiological processes, including cardiovascular biology, inflammation and immunity, neurodegeneration, thrombosis, and hemostasis. A comprehensive understanding of the mechanisms underlying functional interactions with multiple receptor proteins and how these interactions take part in the development of various pathobiological processes may give rise to novel diagnostic and therapeutic strategies. In this review, we summarize the current research linking the role of GRKs to various aspects of cell biology, pathology, and therapeutics, with a particular focus on thrombosis and hemostasis.     

In Vitro and Vivo Identification,Metabolism and Action of Xenoestrogens: An Overview

Xenoestrogens (XEs) are substances that imitate endogenous estrogens to affect the physiologic functions of humans or other animals. As endocrine disruptors, they can be either synthetic or natural chemical compounds derived from diet, pesticides, cosmetics, plastics, plants, industrial byproducts, metals, and medications. By mimicking the chemical structure that is naturally occurring estrogen compounds, synthetic XEs, such as polychlorinated biphenyls (PCBs), bisphenol A (BPA), and diethylstilbestrol (DES), are considered the focus of a group of exogenous chemical. On the other hand, nature phytoestrogens in soybeans can also serve as XEs to exert estrogenic activities. In contrast, some XEs are not similar to estrogens in structure and can affect the physiologic functions in ways other than ER-ERE ligand routes. Studies have confirmed that even the weakly active compounds could interfere with the hormonal balance with persistency or high concentrations of XEs, thus possibly being associated with the occurrence of the reproductive tract or neuroendocrine disorders and congenital malformations. However, XEs are most likely to exert tissue-specific and non-genomic actions when estrogen concentrations are relatively low. Current research has reported that there is not only one factor affected by XEs, but opposite directions are also found on several occasions, or even different components stem from the identical endocrine pathway; thus, it is more challenging and unpredictable of the physical health. This review provides a summary of the identification, detection, metabolism, and action of XEs. However, many details of the underlying mechanisms remain unknown and warrant further investigation.     

An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions

Obesity has become a global epidemic that has a negative impact on population health and the economy of nations. Genetic predispositions have been demonstrated to have a substantial role in the unbalanced energy metabolism seen in obesity. However, these genetic variations cannot entirely explain the massive growth in obesity over the last few decades. Accumulating evidence suggests that modern lifestyle characteristics such as the intake of energy-dense foods, adopting sedentary behavior, or exposure to environmental factors such as industrial endocrine disruptors all contribute to the rising obesity epidemic. Recent advances in the study of DNA and its alterations have considerably increased our understanding of the function of epigenetics in regulating energy metabolism and expenditure in obesity and metabolic diseases. These epigenetic modifications influence how DNA is transcribed without altering its sequence. They are dynamic, reflecting the interplay between the body and its surroundings. Notably, these epigenetic changes are reversible, making them appealing targets for therapeutic and corrective interventions. In this review, I discuss how these epigenetic modifications contribute to the disordered energy metabolism in obesity and to what degree lifestyle and weight reduction strategies and pharmacological drugs can restore energy balance by restoring normal epigenetic profiles.     

Mineralization of bisphenol A by advanced oxidation processes

BACKGROUND: Endocrine disruptors, as in the case of bisphenol A (BPA), are increasingly found in aqueous effluents. The degree of mineralization of a bisphenol A (BPA) aqueous solution after applying several oxidation treatments has been investigated. RESULTS: UV‐C photolysis of BPA allowed calculation of the quantum yield, ϕ_λ=254 = 0.045 ± 0.005 mol Einstein⁻¹ but only 15% of the initial organic carbon content (TOC) was eliminated. Better results (80% conversion) were obtained after TiO₂ addition. Ozone inmediately reacts with BPA. Again, TiO₂ addition in the presence of O₃ was capable of increasing the mineralization level (60%). The photolytic ozonation of BPA was capable of completely eliminating TOC. The presence of activated carbon in the O₃/UV and O₃/UV/TiO₂ systems significantly enhanced the TOC removal reaction rate (100% conversion in 20 min). CONCLUSIONS: Processes such as ozonation or photolysis are capable of efficiently removing BPA from water however, mineralization levels are rather low. Addition of TiO₂ to O₃ or UV‐C significantly enhances TOC removal. The remaining organics still account for an average 20–40% of the initial organic carbon. The combination of O₃/UV‐C is capable of completely mineralizing BPA. Activated carbon and/or TiO₂ addition to the system O₃/UV‐C improves the TOC depletion rate. Copyright © 2008 Society of Chemical Industry     

Zinc as an Imaging Biomarker of Prostate Cancer

Zinc has long been the focus of many biological investigations because of its essential role in biology including a catalytic role in many enzymes, a structural role in the many zinc finger proteins, and a physiological role in many secretory cell processes. Divalent zinc is known to be highly abundant in healthy prostate tissues and lower in prostate cancer (PCa). Given the need for newer diagnostic methods for detection of prostate cancer, zinc-responsive probes of various types have been considered as imaging tools for detecting tissue levels of zinc. Among them, recent zinc-responsive MRI probes show great promise for non-invasive detection of zinc ion secretion from the prostate and other tissues in vivo. In this review, we summarize the need for new diagnostic tools and demonstrate how responsive zinc probes and MRI could satisfy this unmet need.