Endocrine Disruptor Chemicals and Children's Health.

We are all exposed to endocrine-disrupting chemicals (EDCs) starting from embryonic life. The fetus and child set up crucial developmental processes allowing adaptation to the environment throughout life: they are extremely sensitive to very low doses of hormones and EDCs because they are developing organisms. Considering the developmental origin of well-being and diseases, every adult organism expresses consequences of the environment in which it developed. The molecular mechanisms through which the main EDCs manifest their effects and their potential association with endocrine disorders, such as diabetes, obesity, thyroid disease and alteration of adrenal hormones, will be reviewed here. Despite 40 years having passed since the first study on EDCs, little is yet known about them; therefore, our purpose is to take stock of the situation to establish a starting point for further studies. Since there is plenty of evidence showing that exposure to EDCs may adversely impact the health of adults and children through altered endocrine function-suggesting their link to endocrinopathies-it is essential in this context to bear in mind what is already known about endocrine disruptors and to deepen our knowledge to establish rules of conduct aimed at limiting exposure to EDCs' negative effects. Considering that during the COVID-19 pandemic an increase in endocrine disruptor effects has been reported, it will also be useful to address this new phenomenon for better understanding its basis and limiting its consequences.

FATE OF THE FACE MASKS IN THE ENVIRONMENT AFFECT HUMAN AND WILDLIFE: TONS OF FACE MASKS ARE NEW SOURCE FOR THE ENDOCRINE DISRUPTING CHEMICALS

COVID-19 pandemic has become a major public health problem affecting the lives of billions of people worldwide. There is an effective vaccine treatment for the coronavirus infection, but self-isolation and self-protection are the important options to stop the spread of the virus. Usage of the surgical and other face masks are must during COVID-19 pandemic and millions of used masks are accumulating as trash in the environment every day worldwide. Face masks are made of plastic materials mainly polypropylene which is categorized as endocrine disruptor affecting both humans and wildlife. Contamination of face masks to soil, oceans, sea and air may have increased the amount of microplastics concentration and these microplastics from the face masks may have various negative effects on the environment. However, what needs to be done to protect the environment and public health is to dispose of these masks in a very convenient way. Therefore, accurate elimination and collection of used face masks from the environment should be considered to protect our world. Nowadays there are different types of vaccines are in the protecting against death, hospitalization and seriousness of the COVID-19 infection but using face masks are simple, seems safe and effective way from protection against the disease. In this review, we aimed to draw attention to the fact that a using a face mask is very important for staying safe, but they may cause environmental pollution and have adverse effects on directly health and environment.

Evaluation of EFSA training courses on principles in chemical and biological risk assessment

This report evaluates the training courses delivered under the contract OC/EFSA/SCN1 -https://media.proquest.com/media/hms/PFT/1/vIJ9N?_a=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%3D%3D&_s=2ZOX7J4w4lftnvbm53vy0sKE9lQ%3D ER/2017/01 ‐ Lot 1. Within the period of January 2018 to February 2022 a total of 21 training courses were provided, eight on‐site training courses in Parma at EFSA, six virtual training courses during the Covid‐19 pandemic and seven eLearning courses comprising various numbers of modules.The courses covered different aspects of chemical and biological risk assessment and related tools, namely i) harmonisation of risk assessment methodologies for human health and ecological risk assessment of combined exposure to multiple chemicals (mixture assessment), ii) risk assessment of the application of nanoscience and nanotechnologies in agro/food/feed (nanotoxicity);iii) science‐based criteria for identifying endocrine disruptors in the context of EU legislation on pesticides and biocides (endocrine disruption);iv) principles on genotoxicity on scientific assessment (genotoxicity) and v) computational toxicology approaches and tools (in silico). All tutors were experts in their field and had previously performed training courses on these topics.The target participants of the training courses were members of EFSA’s Scientific Committee/Panels and their working groups as well as employees from national and international regulatory agencies associated with risk assessment of feed and food compounds. Members of the EFSA Networks as well as EFSA scientific staff also participated in the training courses.Courses were evaluated based on the feedback of participants and continuously improved also by integrating updated or new EFSA guidance documents.

OBEMIRISK‐Knowledge platform for assessing the risk of bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers

“Obemirisk – Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers” was a knowledge transfer project funded by the European Food Safety Authority (EFSA) that integrated a multidisciplinary team from Spain, France, Belgium, Slovakia and Poland. This project aimed to strengthen the knowledge capacity to assess the risk of bisphenol A and several structural analogues on gut microbiota that could mediate the obesogenic phenotype in childhood. Protocols and methodologies from different fields such as chemical analysis (food and biosamples), nutrition (surveys and questionnaires), microbiology (culturomics and metagenomics), and gene reporter assay (AhR‐Ligand) have been applied and shared. Several data generated under the project are available under open publications and databases for the Consortium and scientific community. Common documents and publications integrating data from endocrine disrupting chemicals (EDCs), bisphenols, microbiota dysbiosis and obesity were elaborated. A networking and specific capacity‐building programmes have been implemented to produce and share the new data on bisphenols data food composition, microbiota and its impact on obesity between providers and recipients’ partners. Scientific exchanges and specific designed courses provided training for students in the risk characterization related domains. The project was mainly focused on the bisphenols´ presence in consumed foods by Spanish children and in several children biosamples (saliva, urine, nails, and hair). Moreover, a pilot project on obese vs. normal‐weight children allowed to determine the obesity‐linked microbiota dysbiosis through metagenomics and specific biomarkers of the dysregulated microbiota‐immune system axis (AhR‐Ligands). The Obemirisk project applied a collaborative and multidisciplinary approach to establish scientific data compilation for harmonising risk assessment and to perform trainings on next generation of risk assessment where microbiome disruption might become a robust biomarker to be used in food safety. Several aspects of the process of capacity building have been mainly conceptual due to the COVId‐19 pandemic and will be further implemented through presential exchanges. Moreover, the consortium work strategy can also propose further EU collaborations for refining and elucidating the impact and mechanisms of bisphenols altering human microbiomes and triggering obesity. The knowledge, analyses and the integrative approach will be extrapolated for other foods, age ranges, geographical areas, and other biomatrices.For grant agreements: © OBEMIRISK consortium, 2022

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.

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.

Surgical face masks as a source of emergent pollutants in aquatic systems: Analysis of their degradation product effects in Danio rerio through RNA-Seq.

Surgical face masks are the most popularised and effective personal equipment for protecting public health during the COVID-19 pandemic. They are composed of plastic polymer fibres with a large amount of inorganic and organic compounds that can be released into aquatic environments through degradation processes. This source of microplastics and inorganic and organic substances could potentially impact aquatic organisms. In this study, the toxicogenomic effects of face masks at different stages of degradation in water were analysed in zebrafish larvae (Danio rerio) through RNA-Seq. Larvae were exposed for 10 days to three treatments: 1) face mask fragments in an initial stage of degradation (poorly degraded masks -PDM- products) with the corresponding water; 2) face mask fragments in an advanced stage of degradation (highly degraded masks -HDM- products) with the corresponding water; and 3) water derived from HDM (W-HDM). Transcriptome analyses revealed that the three treatments provoked the down-regulation of genes related to reproduction, especially the HDM products, suggesting that degradation products derived from face masks could act as endocrine disruptors. The affected genes are involved in different steps of reproduction, including gametogenesis, sperm-egg recognition and binding or fertilisation. Immune-related genes and metabolic processes were also differentially affected by the treatments.

Factors regulating dynamics of angiotensin-converting enzyme-2 (ACE2), the gateway of SARS-CoV-2: Epigenetic modifications and therapeutic interventions by epidrugs.

Angiotensin-converting enzyme-2 (ACE2) is one of the major components of the renin-angiotensin system (RAS) and participates in the physiological functions of the cardiovascular system and lungs. Recent studies identified ACE2 as the receptor for the S-protein of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and thus acts as the gateway for viral entry into the human body. Virus infection causes an imbalance in the RAS axis and induces acute lungs injury and fibrosis. Various factors regulate ACE2 expression patterns as well as control its epigenetic status at both transcription and translational levels. This review is mainly focused on the impact of environmental toxicants, drugs, endocrine disruptors, and hypoxia as controlling parameters for ACE2 expression and its possible modulation by epigenetic changes which are marked by DNA methylation, histone modifications, and micro-RNAs (miRNAs) profile. Furthermore, we have emphasized on interventions of various phytochemicals and bioactive compounds as epidrugs that regulate ACE2-S-protein interaction and thereby curb viral infection. Since ACE2 is an important component of the RAAS axis and a crucial entry point of SARS-CoV-2, the dynamics of ACE2 expression in response to various extrinsic and intrinsic factors are of contemporary relevance. We have collated updated information on ACE2 expression modulated by epidrugs, and urge to take over further studies on these important physiological regulators to unravel many more systemic linkages related to both metabolic and infectious diseases, in general and SARS-CoV-2 in particular for further development of targeted interventions.

Interplay Between Endocrine Disruptors and Immunity: Implications for Diseases of Autoreactive Etiology.

The sex-bias of disease susceptibility has remained a puzzling aspect of several autoimmune conditions, including post-infection viral autoimmunity. In the last half of the twentieth century, the incidence rate of female-biased autoimmunity has steadily increased independent of medical advances. This has suggested a role for environmental factors, such as endocrine disrupting chemicals, which have been described to interfere with endocrine signaling. Endocrine involvement in the proper function of innate and adaptive immunity has also been defined, however, these two areas have rarely been reviewed in correlation. In addition, studies addressing the effects of endocrine disruptors have reported findings resulting from a broad range of exposure doses, schedules and models. This experimental heterogeneity adds confusion and may mislead the translation of findings to human health. Our work will normalize results across experiments and provide a necessary summary relevant to human exposure. Through a novel approach, we describe how different categories of ubiquitously used environmental endocrine disruptors interfere with immune relevant endocrine signaling and contribute to autoimmunity. We hope this review will guide identification of mechanisms and concentration-dependent EDC effects important not only for the sex-bias of autoimmunity, but also for other conditions of immune dysfunction, including post-infection autoreactivity such as may arise following severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, Herpes Simplex virus.

Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERß), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.