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1.
Per- and poly-fluoroalkyl substances (PFAS) and female reproductive outcomes: PFAS elimination, endocrine-mediated effects, and disease.
Rickard, BP, Rizvi, I, Fenton, SE
Toxicology. 2022;:153031
Abstract
Per- and poly-fluoroalkyl substances (PFAS) are widespread environmental contaminants frequently detected in drinking water supplies worldwide that have been linked to a variety of adverse reproductive health outcomes in women. Compared to men, reproductive health effects in women are generally understudied while global trends in female reproduction rates are declining. Many factors may contribute to the observed decline in female reproduction, one of which is environmental contaminant exposure. PFAS have been used in home, food storage, personal care and industrial products for decades. Despite the phase-out of some legacy PFAS due to their environmental persistence and adverse health effects, alternative, short-chain and legacy PFAS mixtures will continue to pollute water and air and adversely influence women's health. Studies have shown that both long- and short-chain PFAS disrupt normal reproductive function in women through altering hormone secretion, menstrual cyclicity, and fertility. Here, we summarize the role of a variety of PFAS and PFAS mixtures in female reproductive tract dysfunction and disease. Since these chemicals may affect reproductive tissues directly or indirectly through endocrine disruption, the role of PFAS in breast, thyroid, and hypothalamic-pituitary-gonadal axis function are also discussed as the interplay between these tissues may be critical in understanding the long-term reproductive health effects of PFAS in women. A major research gap is the need for mechanism of action data - the targets for PFAS in the female reproductive and endocrine systems are not evident, but the effects are many. Given the global decline in female fecundity and the ability of PFAS to negatively impact female reproductive health, further studies are needed to examine effects on endocrine target tissues involved in the onset of reproductive disorders of women.
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2.
Environmental risk factors of type 2 diabetes-an exposome approach.
Beulens, JWJ, Pinho, MGM, Abreu, TC, den Braver, NR, Lam, TM, Huss, A, Vlaanderen, J, Sonnenschein, T, Siddiqui, NZ, Yuan, Z, et al
Diabetologia. 2022;(2):263-274
Abstract
Type 2 diabetes is one of the major chronic diseases accounting for a substantial proportion of disease burden in Western countries. The majority of the burden of type 2 diabetes is attributed to environmental risks and modifiable risk factors such as lifestyle. The environment we live in, and changes to it, can thus contribute substantially to the prevention of type 2 diabetes at a population level. The 'exposome' represents the (measurable) totality of environmental, i.e. nongenetic, drivers of health and disease. The external exposome comprises aspects of the built environment, the social environment, the physico-chemical environment and the lifestyle/food environment. The internal exposome comprises measurements at the epigenetic, transcript, proteome, microbiome or metabolome level to study either the exposures directly, the imprints these exposures leave in the biological system, the potential of the body to combat environmental insults and/or the biology itself. In this review, we describe the evidence for environmental risk factors of type 2 diabetes, focusing on both the general external exposome and imprints of this on the internal exposome. Studies provided established associations of air pollution, residential noise and area-level socioeconomic deprivation with an increased risk of type 2 diabetes, while neighbourhood walkability and green space are consistently associated with a reduced risk of type 2 diabetes. There is little or inconsistent evidence on the contribution of the food environment, other aspects of the social environment and outdoor temperature. These environmental factors are thought to affect type 2 diabetes risk mainly through mechanisms incorporating lifestyle factors such as physical activity or diet, the microbiome, inflammation or chronic stress. To further assess causality of these associations, future studies should focus on investigating the longitudinal effects of our environment (and changes to it) in relation to type 2 diabetes risk and whether these associations are explained by these proposed mechanisms.
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3.
Environmental Determinants of Type 1 Diabetes: From Association to Proving Causality.
Quinn, LM, Wong, FS, Narendran, P
Frontiers in immunology. 2021;:737964
Abstract
The rising incidence of type 1 diabetes (T1D) cannot be ascribed to genetics alone, and causative environmental triggers and drivers must also be contributing. The prospective TEDDY study has provided the greatest contributions in modern time, by addressing misconceptions and refining the search strategy for the future. This review outlines the evidence to date to support the pathways from association to causality, across all stages of T1D (seroconversion to beta cell failure). We focus on infections and vaccinations; infant growth and childhood obesity; the gut microbiome and the lifestyle factors which cultivate it. Of these, the environmental determinants which have the most supporting evidence are enterovirus infection, rapid weight gain in early life, and the microbiome. We provide an infographic illustrating the key environmental determinants in T1D and their likelihood of effect. The next steps are to investigate these environmental triggers, ideally though gold-standard randomised controlled trials and further prospective studies, to help explore public health prevention strategies.
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4.
Perspective on prenatal polychlorinated biphenyl exposure and the development of the progeny nervous system (Review).
Wang, Y, Hu, C, Fang, T, Jin, Y, Wu, R
International journal of molecular medicine. 2021;(2)
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Abstract
The developmental origins of health and disease concept illustrates that exposure in early life to various factors may affect the offspring's long‑term susceptibility to disease. During development, the nervous system is sensitive and vulnerable to the environmental insults. Polychlorinated biphenyls (PCBs), which are divided into dioxin‑like (DL‑PCBs) and non‑dioxin‑like PCBs (NDL‑PCBs), are synthetic persistent environmental endocrine‑disrupting chemicals. The toxicological mechanisms of DL‑PCBs have been associated with the activation of the aryl hydrocarbon receptor and NDL‑PCBs have been associated with ryanodine receptor‑mediated calcium ion channels, which affect neuronal migration, promote dendritic growth and alter neuronal connectivity. In addition, PCB accumulation in the placenta destroys the fetal placental unit and affects endocrine function, particularly thyroid hormones and the dopaminergic system, leading to neuroendocrine disorders. However, epidemiological investigations have not achieved a consistent result in different study cohorts. The present review summarizes the epidemiological differences and possible mechanisms of the effects of intrauterine PCB exposure on neurological development.
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A clandestine culprit with critical consequences: Benzene and acute myeloid leukemia.
Shallis, RM, Weiss, JJ, Deziel, NC, Gore, SD
Blood reviews. 2021;:100736
Abstract
While most clinicians recognize adult therapy-related leukemias following cytotoxic chemotherapy and radiation, environmental regulatory agencies evaluate exposure to "safe levels" of leukemogenic compounds. Benzene represents the most notorious leukemogenic chemical. Used in the production of ubiquitous items such as plastics, lubricants, rubbers, dyes, and pesticides, benzene may be responsible for the higher risk of acute myeloid leukemia (AML) among automobile, janitorial, construction, and agricultural workers. It is possible that ambient benzene may contribute to many cases of "de novo" AML not arising out of germline predispositions. In this appraisal of the available literature, we evaluate and discuss the association between chronic, low-dose and ambient exposure to environmental benzene and the development of adult AML.
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Air pollution and pre-eclampsia; associations and potential mechanisms.
Bearblock, E, Aiken, CE, Burton, GJ
Placenta. 2021;:188-194
Abstract
INTRODUCTION Air pollution has significant negative health impacts, particularly on the cardiovascular system. The aims of this narrative review were to identify whether there is an association between air pollution and the incidence of pre-eclampsia, and the potential mechanisms by which any effects may be mediated. METHODS We undertook a literature search using Google Scholar, PubMed, the Cochrane Library and NICE Evidence. The primary eligibility criterion was articles correlating exposure to air pollution with incidence of pre-eclampsia. RESULTS Meta-analyses currently show a positive association between pre-eclampsia and exposure to both particulate matter PM2.5 and nitrogen dioxide, but no significant associations with ambient ozone or carbon monoxide exposure. No meta-analysis has been performed for exposure to sulfur dioxide. Variability in terms of quantification of exposure, the exposure period and co-founders among the studies makes comparisons complex. Adverse effects on trophoblast invasion and placental vascularisation, and increases in oxidative stress and anti-angiogenic factors, such as sFlt-1, in response to air pollution provide pathways by which exposure may contribute to the pathophysiology of pre-eclampsia. So far, studies have not discriminated between the early- and late-onset forms of the syndrome. DISCUSSION Future prospective studies using personal air pollution monitors and blood biomarkers of pre-eclampsia would strengthen the associations. Interactions between pollutants are poorly documented, and at present there is minimal informed advice available to women on the need to avoid exposure to air pollutants during pregnancy.
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Air Pollution and Asthma: Mechanisms of Harm and Considerations for Clinical Interventions.
Pfeffer, PE, Mudway, IS, Grigg, J
Chest. 2021;(4):1346-1355
Abstract
There is global concern regarding the harmful impact of polluted air on the respiratory health of patients with asthma. Multiple epidemiologic studies have shown ongoing associations between high levels of air pollution and poor early life lung growth, development of allergic sensitization, development of asthma, airway inflammation, acutely impaired lung function, respiratory tract infections, and asthma exacerbations. However, studies have often yielded inconsistent findings, and not all studies have found significant associations; this may be related to both variations in statistical, measurement, and modeling methodologies between studies as well as differences in the concentrations and composition of air pollution globally. Overall, this variation in findings suggests we still do not fully understand the effects of ambient pollution on the lungs and on the evolution and exacerbation of airway diseases. There is clearly a need to augment epidemiologic studies with experimental studies to clarify the underlying mechanistic basis for the adverse responses reported and to identify the key gaseous and particle-related components within the complex air pollution mixture driving these outcomes. Some progress toward these aims has been made. This article reviews studies providing an improved understanding of causal pathways linking air pollution to asthma development and exacerbation. The article also considers potential strategies to reduce asthma morbidity and mortality through regulation and behavioral/pharmacologic interventions, including a consideration of pollutant avoidance strategies and antioxidant and/or vitamin D supplementation.
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8.
Mitochondrion: a sensitive target for Pb exposure.
Han, Q, Zhang, W, Guo, J, Zhu, Q, Chen, H, Xia, Y, Zhu, G
The Journal of toxicological sciences. 2021;(8):345-358
Abstract
Pb exposure is a worldwide environmental contamination issue which has been of concern to more and more people. Exposure to environmental Pb and its compounds through food and respiratory routes causes toxic damage to the digestive, respiratory, cardiovascular and nervous systems, etc. Children and pregnant women are particularly vulnerable to Pb. Pb exposure significantly destroys children's learning ability, intelligence and perception ability. Mitochondria are involved in various life processes of eukaryotes and are one of the most sensitive organelles to various injuries. There is no doubt that Pb-induced mitochondrial damage can widely affect various physiological processes and cause great harm. In this review, we summarized the toxic effects of Pb on mitochondria which led to various pathological processes. Pb induces mitochondrial dysfunction leading to the increased level of oxidative stress. In addition, Pb leads to cell apoptosis via mitochondrial permeability transition pore (MPTP) opening. Also, Pb can stimulate the development of mitochondria-mediated inflammatory responses. Furthermore, Pb triggers the germination of autophagy via the mitochondrial pathway and induces mitochondrial dysfunction, disturbing intracellular calcium homeostasis. In a word, we discussed the effects of Pb exposure on mitochondria, hoping to provide some references for further research and better therapeutic options for Pb exposure.
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The effect of endocrine disruptors on the reproductive system - current knowledge.
Czarnywojtek, A, Jaz, K, Ochmańska, A, Zgorzalewicz-Stachowiak, M, Czarnocka, B, Sawicka-Gutaj, N, Ziółkowska, P, Krela-Kaźmierczak, I, Gut, P, Florek, E, et al
European review for medical and pharmacological sciences. 2021;(15):4930-4940
Abstract
OBJECTIVE Chemicals that disrupt the endocrine homeostasis of the human body, otherwise known as endocrine disruptors (EDCs), are found in the blood, urine, amniotic fluid, or adipose tissue. This paper presents the current knowledge about EDCs and the reproductive system. MATERIALS AND METHODS The article is an overview of the impact of EDCs and their mechanism of action, with particular emphasis on gonads, based on the information available on medical databases (PubMed, Web of Science, EMBASE and Google Scholar, EMBASE and Web of Science) until May 2021. RESULTS EDCs occur in everyday life, e.g., they are components of adhesives, brake fluids, and flame retardants; they are used in the production of polyvinyl chloride (PVC), plastic food boxes, pacifiers, medicines, cosmetics (bisphenol A, phthalates), hydraulic fluids, printing inks (polychlorinated biphenyls - PCBs), receipts (bisphenol A, BSA) and raincoats (phthalates); they are also a component of polyvinyl products (e.g. toys) (phthalates), air fresheners and cleaning agents (phthalates); moreover, they can be found in the smoke from burning wood (dioxins), and in soil or plants (pesticides). EDCs are part of our diet and can be found in vegetables, fruits, green tea, chocolate and red wine (phytoestrogens). In addition to infertility, they can lead to premature puberty and even cause uterine and ovarian cancer. However, in men, they reduce testosterone levels, reduce the quality of sperm, and cause benign testicular tumors. CONCLUSIONS Therefore, this article submits that EDCs negatively affect our health, disrupting the functioning of the endocrine system, and particularly affecting the functioning of the gonads.
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10.
An overview on possible links between aflatoxin B1 exposure and gallbladder cancer.
Costa, J, Lima, N, Santos, C
Mycotoxin research. 2021;(3):205-214
Abstract
Gallbladder cancer (GBC) is one of the most common sites for biliary tract cancers. It has a worldwide distribution being endemic in South America and Southern Asia. These high GBC rates have previously been linked to the determinants of health such as nutrition, genetics, lifestyle, and environment. Exposure to aflatoxin B1 (AFB1), a human carcinogen, is suggested to be involved with GBC development. This work aims to analyse the interplay of social, lifestyle, and genetic predisposing factors to GBC. AFB1 plays a pivotal role in carcinogenic onset by genetic and epigenetic modifications. AFB1 can induce molecular changes involved in the GBC pathogenesis, such as overexpression of UCHL1 gene, mutagenesis of TP53 gene, abnormal expression of oncogenes BCL-2, and aberrantly methylation of ERBB family receptors. However, a large-scale scientific cooperation is needed to confirm these molecular links through which AFB1 may increase the GBC risk. For that, monitoring AFB1 exposure through AF-albumin and AFB1-lysine will clarify the level of exposure of the population to AFB1 in the GBC hotspot. Further, analyses of AFB1-adduct concentrations in GBC cases (fatal and non-fatal) are needed to understanding if AF contamination can trigger gallbladder cancer.