Toxic Chemicals In Environment Research Articles

Highly sensitive response to the toxicity of environmental chemicals in transparent casper zebrafish

The response sensitivity to toxic substances is the most concerned performance of animal model in chemical risk assessment. Casper (mitfaw2/w2;mpv17a9/a9), a transparent zebrafish mutant, is a useful in vivo model for toxicological assessment. However, the ability of casper to respond to the toxicity of exogenous chemicals is unknown. In this study, zebrafish embryos were exposed to five environmental chemicals, chlorpyrifos, lindane, α-endosulfan, bisphenol A, tetrabromobisphenol A (TBBPA), and an antiepileptic drug valproic acid. The half-lethal concentration (LC50) values of these chemicals in casper embryos were 62–87 % of that in the wild-type. After TBBPA exposure, the occurrence of developmental defects in the posterior blood island of casper embryos was increased by 67–77 % in relative to the wild-type, and the half-maximal effective concentration (EC50) in casper was 73 % of that in the wild type. Moreover, the casper genetic background significantly increased the hyperlocomotion caused by chlorpyrifos and lindane exposure compared with the wild type. These results demonstrated that casper had greater susceptibility to toxicity than wild-type zebrafish in acute toxicity, developmental toxicity and neurobehavioral toxicity assessments. Our data will inform future toxicological studies in casper and accelerate the development of efficient approaches and strategies for toxicity assessment via the use of casper.

Additive-free electroless deposition on graphene/copper foil: Photo-induced and defect-assisted approach for environmentally friendly plating

The environmental toxicity of chemicals used in electroless plating process is often overlooked. In fact, the wastewater from the electroless plating process contains metal complexes, reducing agents and stabilizers that can create hazard to our environment. To address this concern, an additive-free electroless deposition process on graphene/Cu foil is proposed. The defect structure of graphene plays a pivotal role by acting as a reservoir for concentrating photoelectrons generated from ultra-thin cuprous oxide (Cu2O) located at the interface of graphene and Cu foil upon exposure to light irradiation. In the Cu ion solution, Cu ions were anchored on the defect sites and formed a Cu-C4 structure with graphene. The Cu-C4 sites accumulate abundant photoelectrons and trigger the reduction of Cu ions to form island-like growth of Cu, which immediately was oxidized to Cu2O, leaving only a small portion of metallic Cu. Concurrently, the presence of Cu ions induces the generation of additional defect sites on graphene, providing further growth sites for Cu deposition. This process continues until the entire graphene surface is covered by the deposited Cu2O. Ultimately, the deposition of metallic oxides with lower redox potential can be achieved. The proposed deposition mechanism assisted by irradiation of photocatalyst and defect structure of graphene material provides a truly environmentally friendly electroless plating process. By eliminating the need for additives and significantly reducing the environmental hazards associated with electroless plating, this method holds great promise for sustainable materials manufacturing.

Production and Characterization of Pellets from Agricultural Residue: Cotton, Tur, and Soybean

Substituting biomass for conventional sources of fuel can help to provide cleaner energy. Woody biomass pellets are gaining popularity in the primary energy industry. Agricultural biomass is either burned on the farm or used as fodder for animals recently, which releases toxic chemicals in environment. Locally cultivated crop waste has potential to be more environmentally benign than imported biomass. As a result, residues of locally grown Cotton, Tur, and Soybean crops were used for pelleting in this study. The collected residues were sundried and shredded to particle sizes ranging between 2.36 mm to 4.75mm. The pellets were prepared without binder by using pelleting machine. The proximate and ultimate analysis of crop residue and pellet samples was carried out to check characteristics and applicability of pellets as bioenergy source. The thermogravimetric analysis was conducted to check thermal behaviour and SEM-EDS analysis was carried out to detect the inorganics present in ash sample. The obtained calorific values of cotton, tur, and soybean pellets are 3696.57, 3487.83, and 3281.65 Kcal/Kg respectively and moisture content is below 10% for all three types of pellets. The findings showed that crop residue pellets as an alternative to conventional fuel sources provide superior economic and environmental outcomes.

Decline in human sperm parameters: How to stop?

A large systematic review and meta-regression analysis found that sperm counts all over the world appeared to be declining rather than stabilizing. The decline in male sperm counts does not necessarily translate to a decline in male fertility. The cause of declining sperm counts remains unknown; however, several potential causative factors have been identified: 1. Chronic diseases: diabetes mellitus, hypertension; hyperlipidemia, hyperuricemia and skin Diseases & metabolic syndrome. 2. Environmental factors: bisphenol a; phthalates; heavy metals and heat. 3. Lifestyle: obesity, diet, tobacco, alcohol, marijuana, stress, reduced sleep & sedentary life. Addressing these causes is required to stop or decrease male fertility decline. Action to improve semen quality such as prevention & treatment of chronic disease, decreasing unhealthy lifestyle behaviors such as smoking, poor diet, or lack of physical activity & eliminating toxic environmental chemicals.

Exposure to Polycyclic Aromatic Hydrocarbons and adverse reproductive outcomes in women: current status and future perspectives.

Polycyclic Aromatic Hydrocarbons (PAHs) are ubiquitous, toxic environmental chemicals that can cause adverse reproductive health effects. The objectives of this mini-review are to highlight the adverse reproductive outcomes due to PAH exposure with the main focus on polycystic ovary syndrome (PCOS) and premature ovarian failure (POF) and to provide perspectives on future research needs. We reviewed studies that have reported the adverse reproductive outcomes associated with PAHs exposures in women through a comprehensive search of bibliographic databases and gray literature sources. In addition, potentially modifiable sources of exposure to PAHs and associated reproductive outcomes were also investigated. A total of 232 papers were retrieved through a comprehensive search of bibliographic databases, out of which three studies met the eligibility criteria and were included in the review. Results showed that exposure to PAHs is associated with adverse reproductive outcomes defined as PCOS, POF, and reproductive hormone imbalance. Sources of PAH exposure associated with adverse reproductive outcomes include active and passive tobacco smoking, specific cooking methods, and pesticides. Future studies are warranted to examine the mechanisms by which PAHs result in adverse reproductive endpoints in women. Further, environmental exposures that are potentially modifiable such as exposure to tobacco smoke, may contribute to PAH exposure, and these exposures should be targeted in future policies and interventions.

Disruption of the tumor suppressor-like activity of aryl hydrocarbon receptor by arsenic in epithelial cells and human lung cancer.

As the most classic and extensively studied transcription factor in response to environmental toxic chemicals, the human aryl hydrocarbon receptor (AHR) has been implicated in mediating some oncogenic responses also. Limited information is available, however, on whether arsenic, a widely presented environmental carcinogen, can regulate AHR to exert its carcinogenic activity. Through chromatin immunoprecipitation and sequencing (ChIP-seq), CRISPR-Cas9 gene editing, RNA-seq, and immunohistochemistry (IHC), in this report we provided evidence showing that arsenic enforces TGFβ and other oncogenic signaling pathways in bronchial epithelial cells through disrupting the tumor suppressor-like activity of AHR. AHR is normally enriched on a number of oncogenic genes in addition to the known phase I/II enzymes, such as genes in TGFβ and Nrf2 signaling pathways and several known oncogenes. Arsenic treatment substantially reduced the binding of AHR on these genes followed by an increased expression of these genes. CRISPR-Cas9-based knockout of AHR followed by RNA-seq further demonstrated increased expression of the TGFβ signaling and some oncogenic signaling pathway genes in the AHR knockout cells. IHC studies on human tissue samples revealed that normal human lung tissues expressed high level of AHR. In contrast, the AHR expression was diminished in the lung cancer tissues. Accordingly, the data from this study suggest that AHR has tumor suppressor-like activity for human lung cancer, and one of the carcinogenic mechanisms of arsenic is likely mediated by the inhibition of arsenic on the tumor suppressor-like activity of AHR.

Predicting Dose-Range Chemical Toxicity using Novel Hybrid Deep Machine-Learning Method.

Humans are exposed to thousands of chemicals, including environmental chemicals. Unfortunately, little is known about their potential toxicity, as determining the toxicity remains challenging due to the substantial resources required to assess a chemical in vivo. Here, we present a novel hybrid neural network (HNN) deep learning method, called HNN-Tox, to predict chemical toxicity at different doses. To develop a hybrid HNN-Tox method, we combined two neural network frameworks, the Convolutional Neural Network (CNN) and the multilayer perceptron (MLP)-type feed-forward neural network (FFNN). Combining the CNN and FCNN in the field of environmental chemical toxicity prediction is a novel approach. We developed several binary and multiclass classification models to assess dose-range chemical toxicity that is trained based on thousands of chemicals with known toxicity. The performance of the HNN-Tox was compared with other machine-learning methods, including Random Forest (RF), Bootstrap Aggregation (Bagging), and Adaptive Boosting (AdaBoost). We also analyzed the model performance dependency on varying features, descriptors, dataset size, route of exposure, and toxic dose. The HNN-Tox model, trained on 59,373 chemicals annotated with known LD50 and routes of exposure, maintained its predictive ability with an accuracy of 84.9% and 84.1%, even after reducing the descriptor size from 318 to 51, and the area under the ROC curve (AUC) was 0.89 and 0.88, respectively. Further, we validated the HNN-Tox with several external toxic chemical datasets on a large scale. The HNN-Tox performed optimally or better than the other machine-learning methods for diverse chemicals. This study is the first to report a large-scale prediction of dose-range chemical toxicity with varying features. The HNN-Tox has broad applicability in predicting toxicity for diverse chemicals and could serve as an alternative methodology approach to animal-based toxicity assessment.

Genotoxicity assessment of per- and polyfluoroalkyl substances mixtures in human liver cells (HepG2)

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, toxic, and persistent environmental chemicals of concern that have been widely detected in all environmental matrices including human biological fluids. Although humans are exposed to complex mixtures of PFAS, it remains uncertain whether the co-exposure to PFAS mixtures could induce genotoxic damage in humans. Hence, this study evaluated the combined genotoxicity of PFAS mixtures in a human cell line system. To assess the possible genotoxic damage caused by human exposure to PFAS and their mixtures, we investigated their potential to induce cytotoxicity (cell viability) and genotoxicity (DNA damage) in a human liver cell line (HepG2). The selected PFAS include perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS). The interaction toxicities of these PFAS in binary mixtures were also determined using the additive index approach. The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures induced a concentration-dependent decrease in cell viability. The additive index values indicated that the binary mixtures of PFOS + PFNA, PFOS + PFDA, and PFOS + PFOA displayed synergistic interaction, whereas the binary mixtures of PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS behaved additively. Using the alkaline Comet assay, the potential of PFAS and their mixtures to induce DNA damage was evaluated based on a 1:1 ratio of the concentration of respective compounds required to produce a 1/10th of effective concentrations causing 50 % inhibition in cell viability (EC50). The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures (PFOS + PFNA, PFOS + PFDA, PFOS + PFOA, PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS) caused a moderate increase in cellular DNA damage, but no dose-response relationship was observed. Overall, this study indicates that the tested PFAS causes a concentration-dependent decrease in cell viability and only a modest increase in cellular DNA damage under these conditions.

Serum levels of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in a sample of Lebanese pregnant women: The role of dietary, anthropometric, and environmental factors

Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are unintentionally produced, toxic environmental chemicals that persist for long years and bioaccumulate along the food chain, contaminating humans through diet. A particularly critical population subgroup is pregnant women given the adverse health effects on fetuses and newborns. Several anthropogenic sources of exposure to PCDD/Fs exist in Lebanon. Therefore, the aim of the present cross-sectional study is to measure the levels of PCDD/Fs in a sample of pregnant women in Lebanon and to explore potential associated factors. In this study, we measured serum concentrations of seven dioxins and ten furans, among 423 pregnant women recruited at delivery, using gas chromatography MS/MS. Among 269 participants, maternal sociodemographic information was collected including vicinity to landfills, incineration, pesticide use, industrial activity, and smoking. Anthropometric data were registered regarding pre-pregnancy body mass index (BMI), pre-pregnancy weight loss from restrictive diet, and gestational weight gain. Intake of major food groups generally related to PCDD/Fs was reported (fish, red meat, poultry, and dairy). Bivariate and multivariate analyses were performed to identify associations. PCDD/Fs were detected in 0 to 56.1% of the sample. Geometric mean concentrations were 75.5 (2.35) pg/g lipid and 2.25 (1.39) TEQ2005 pg/g lipid for total dioxins, and 2.66 (1.76) pg/g lipid and 0.34 (1.78) TEQ2005 pg/g lipid for total furans. Levels were relatively lower than levels previously observed in France, Germany, Mexico, Ghana, and Japan. Red meat consumption was the most consistently associated factor with a 2.38–2.57 fold increase in PCDD/F levels. Pre-pregnancy weight loss showed inverse associations with PCDD/F congeners. Vicinity to illegal incineration was also associated with a 2.32–2.43 fold increase in PCDD/F levels. In conclusion, results showed the importance of dietary, anthropometric, and environmental factors in the present sample's exposure to PCDD/Fs, in a region that contains anthropogenic sources of contamination.

Promising effects of herbal compounds against strongyloidiasis: a systematic review.

Strongyloidiasis could be a significant global health issue undervalued in several countries, which is caused by Strongyloides spp. Challenges stemming from the use of anthelmintic chemotherapy, such as the development of resistance, the progressive cost of medicines, environmental toxicity of chemicals, and residuals in beast products have increased interest in promoting alternative means of control for the use of plant-based parasite control methods. A study on herbal extracts may offer a less expensive yet equally effective alternative for the prevention and treatment of helminthic multi-resistance. We systematically searched the Web of Sciences, PubMed/MEDLINE, and Scopus databases to explore original publications related to medicinal plants and Strongyloides in English on September 29, 2021. The keywords of medicinal plant, traditional medicine, plant extract, herbal medicine, herbal extract, natural drug, Strongyloides, strongyloidiasis, Strongyloides infection, and helminth were used in our search. Researchers can make use of this review as a quick reference. In this study, we have summarized recent advancements and published investigations on herbal and naturally derived medicines in treating strongyloidiasis undertaken by several researchers worldwide. These medicinal herbs, as well as the active and significant compounds they contain, such as alkaloids, phenolic derivatives, tannins, and terpenes, have been outlined in recent articles. Various studies on herbal remedies to treat strongyloidiasis have been undertaken to date, but further research is still required on moderately effective and low harmful substances.

Analysis of Nanomaterials on Biological and Environmental Systems and New Analytical Methods for Improved Detection.

The advancing field of nanoscience has produced lower mass, smaller size, and expanded chemical composition nanoparticles over recent years. These new nanoparticles have challenged traditional analytical methods of qualification and quantification. Such advancements in nanoparticles and nanomaterials have captured the attention of toxicologists with concerns regarding the environment and human health impacts. Given that nanoparticles are only limited by size (1–100 nm), their chemical and physical characteristics can drastically change and thus alter their overall nanotoxicity in unpredictable ways. A significant limitation to the development of nanomaterials is that traditional regulatory and scientific methods used to assess the biological and environmental toxicity of chemicals do not generally apply to the assessment of nanomaterials. Significant research effort has been initiated, but much more is still needed to develop new and improved analytical measurement methods for detecting and quantitating nanomaterials in biological and environmental systems.

A microengineered biomimetic model of the placental barrier to study environmental exposures during pregnancy

Exposure to toxic heavy metals contributes to the development of pregnancy complications that can adversely affect fetal development. Despite increasing evidence suggesting the negative health impact of heavy metals, investigating their adverse effects in the context of human pregnancy remains a major challenge due to the difficulty of human subject research and the limited capacity of animal models to properly represent the anatomy and function of the human reproductive system. Motivated by problem, here we describe a microengineered in vitro model designed to reverse engineer the maternal-fetal interface in the human placenta. This biomimetic system enables advanced capabilities to grow human trophoblast cells and fetal vascular endothelial cells in a physiological spatial arrangement and dynamic culture conditions to engineer the placental barrier in vitro that can emulate regulated material transport between maternal and fetal circulations. Using cadmium (CdCl2 ) as a representative example of heavy metals, we investigate whether and how this environmental chemical affects the human placental barrier and its physiological function as a gatekeeper. Our study also examines the role of membrane transporters in the maternal-to-fetal transfer of cadmium to provide insights into efflux transporter-medicated protection against environmental exposures during pregnancy.We used soft lithography to construct a compartmentalized elastomeric device consisting of two overlapping chambers separated by a thin semipermeable membrane. After sterilization and surface coating with extracellular matrix protein, the device was seeded with BeWo b30 human trophoblast cells and primary human villous endothelial cells on the opposite sides of the membrane. The bi-layer tissue was then cultured under perfusion conditions by using syringe pumps connected to each chamber. To mimic the physiological process of placental development, we treated the trophoblast cell layer in the maternal chamber with forskolin (50 µM) to induce syncytialization.Our microengineered model of the human placental barrier formed a tight barrier (evaluated by expression of E-cadherin and VE-cadherin), secreted the pregnancy hormone human chorionic gonadotropin beta (hCGβ), and supported physiological maternal-to-fetal transport of glucose. Following CdCl2 treatment (0.5-50 µM), we observed concentration-dependent deleterious responses of the maternal and fetal tissues as demonstrated by reduced cell viability and placental hormone secretion, compromised barrier function, and increased secretion of proinflammatory cytokines. The results also indicated upregulated expression of metallothioneins IA and IIA (MT-IA/IIA) metal binding proteins.The placenta-on-a-chip is an innovative and translational in vitro platform for the study of environmental chemical toxicity in the human placenta. With further improvements, this technology may advance our ability to model, interrogate, and predict the potential of xenobiotics to disrupt placentation and maintenance of human pregnancy.

Membrane Lipid Replacement with Glycerolphospholipids Slowly Reduces Self-Reported Symptom Severities in Chemically Exposed Gulf War Veterans

Background: Chemically exposed veterans of the 1991 Gulf War have few options for treatment of conditions and symptoms related to their chemical exposures. Membrane Lipid Replacement (MLR) with oral membrane glycerolphospholipids is a safe and effective method for slowly removing hydrophobic organic molecules from tissues, while enhancing mitochondrial function and decreasing the severity of certain signs and symptoms associated with multi-symptom illnesses. Methods: A preliminary open-label study utilizing 20 male veterans who were deployed to combat areas, exposed to environmental toxic chemicals and subsequently diagnosed with Gulf War Illnesses (GWI) were utilized. These subjects took 6 g per day oral glycerolphospholipids for 6 months, and the severities of over 100 signs and symptoms were self-reported at various times using illness survey forms. Results: In the sixteen patients that fully complied and completed the study, there were gradual and significant reductions of symptom severities in categories related to fatigue, pain, musculoskeletal, nasopharyngeal, breathing, vision, sleep, balance, and urinary, gastrointestinal and chemical sensitivities. There were no adverse incidents during the study, and the all-natural oral study supplement was extremely well tolerated. Conclusions: MLR with oral glycerolphospholipids appears to be a simple, safe and potentially effective method of slowly reducing the severities of multiple symptoms in chemically exposed veterans.

Sentinel animals for monitoring the environmental lead exposure: combination of traditional review and visualization analysis.

In nature, certain animals share a common living environment with humans, thus these animals have become biomonitors of health effects related to various environmental exposures. As one of the most toxic environmental chemicals, lead (Pb) can cause detriment health effects to animals, plants, and even humans through different exposure pathways such as atmosphere, soil, food, water, and dust, etc. Sentinel animals played an "indicative" role in the researches of environmental pollution monitoring and human health. In order to comprehend the usage of sentinel animals in the indication of environmental Pb pollution and human Pb exposure completely, a combination of traditional review and visualization analysis based on CiteSpace literature was used to review earlier researches in this study. In the first instance, present researches on exposure sources and exposure pathways of Pb were summarized briefly, and then the studies using sentinel animals to monitor environmental heavy metal pollution and human health were combed. Finally, visualization software CiteSpace 5.8.R3 was used to explore and analyze the hotspots and frontiers of lead exposure and sentinel animals researches at home and abroad. The results showed that certain mammals were good indicators for human lead exposure. Sentinel animals had been widely used to monitor the ecological environment and human lead exposure. Among them, the blood lead levels of small mammals, particularly for domestic dogs and cats, had a significant correlation with the blood lead levels of human living in the same environment. It indicated that certain biological indicators in animals can be used as surrogates to monitor human body exposure to heavy metals. This study also explored the challenges and perspectives that may be faced in sentinel animal research, in order to provide a certain theoretical basis and train of thought guidance for future research.

A novel chemo-phenotypic method identifies mixtures of salpn, vitamin D3, and pesticides involved in the development of colorectal and pancreatic cancer

Environmental chemical (EC) exposures and our interactions with them has significantly increased in the recent decades. Toxicity associated biological characterization of these chemicals is challenging and inefficient, even with available high-throughput technologies. In this report, we describe a novel computational method for characterizing toxicity, associated biological perturbations and disease outcome, called the Chemo-Phenotypic Based Toxicity Measurement (CPTM). CPTM is used to quantify the EC “toxicity score” (Zts), which serves as a holistic metric of potential toxicity and disease outcome. CPTM quantitative toxicity is the measure of chemical features, biological phenotypic effects, and toxicokinetic properties of the ECs. For proof-of-concept, we subject ECs obtained from the Environmental Protection Agency’s (EPA) database to the CPTM. We validated the CPTM toxicity predictions by correlating ‘Zts’ scores with known toxicity effects. We also confirmed the CPTM predictions with in-vitro, and in-vivo experiments. In in-vitro and zebrafish models, we showed that, mixtures of the motor oil and food additive ‘Salpn’ with endogenous nuclear receptor ligands such as Vitamin D3, dysregulated the nuclear receptors and key transcription pathways involved in Colorectal Cancer. Further, in a human patient derived cell organoid model, we found that a mixture of the widely used pesticides ‘Tetramethrin’ and ‘Fenpropathrin’ significantly impacts the population of patient derived pancreatic cancer cells and 3D organoid models to support rapid PDAC disease progression. The CPTM method is, to our knowledge, the first comprehensive toxico-physicochemical, and phenotypic bionetwork-based platform for efficient high-throughput screening of environmental chemical toxicity, mechanisms of action, and connection to disease outcomes.

Interactions of Environmental Chemicals and Natural Products With ABC and SLC Transporters in the Digestive System of Aquatic Organisms.

An organism’s diet is a major route of exposure to both beneficial nutrients and toxic environmental chemicals and natural products. The uptake of dietary xenobiotics in the intestine is prevented by transporters of the Solute Carrier (SLC) and ATP Binding Cassette (ABC) family. Several environmental chemicals and natural toxins have been identified to induce expression of these defense transporters in fish and aquatic invertebrates, indicating that they are substrates and can be eliminated. However, certain environmental chemicals, termed Transporter-Interfering Chemicals or TICs, have recently been shown to bind to and inhibit fish and mammalian P-glycoprotein (ABCB1), thereby sensitizing cells to toxic chemical accumulation. If and to what extent other xenobiotic defense or nutrient uptake transporters can also be inhibited by dietary TICs is still unknown. To date, most chemical-transporter interaction studies in aquatic organisms have focused on ABC-type transporters, while molecular interactions of xenobiotics with SLC-type transporters are poorly understood. In this perspective, we summarize current advances in the identification, localization, and functional analysis of protective MXR transporters and nutrient uptake systems in the digestive system of fish and aquatic invertebrates. We collate the existing literature data on chemically induced transporter gene expression and summarize the molecular interactions of xenobiotics with these transport systems. Our review emphasizes the need for standardized assays in a broader panel of commercially important fish and seafood species to better evaluate the effects of TIC and other xenobiotic interactions with physiological substrates and MXR transporters across the aquatic ecosystem and predict possible transfer to humans through consumption.

Evaluation of Developmental Toxicity of Environmental Chemicals Using Cultured Neurons

Evaluation of Developmental Toxicity of Environmental Chemicals Using Cultured Neurons

Impacts of PBDE-47 exposure before, during and after pregnancy on the maternal gut microbiome and its association with host metabolism

Maternal gut microbiota play an important role in the modulation of offspring disease susceptibility and gut microbiota dysbiosis has been proposed as a mechanism through which toxic environmental chemicals exert their adverse impacts on health. The brominated flame retardants polybrominated diphenyl ethers (PBDEs) are developmental toxicants and induce dysbiotic gut microbiota in offspring. Yet, whether and how PBDEs impact the maternal gut microbiota remain unclear. Here, we sought to investigate the effect of 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) exposure from preconception through lactation cessation on maternal gut microbiota and its link to host serum metabolic consequences. Female Sprague-Dawley rats were daily exposed to 10 mg/kg PBDE-47 via oral gavage from ten days before conception until offspring were weaned on postnatal day 21, then maternal fecal and blood samples were collected for microbiome and metabolome analyses by using 16S ribosomal RNA gene sequencing and gas chromatography-mass spectrometry, respectively. Maternal exposure to PBDE-47 showed a distinct profile in gut microbiota compared to control dams, as evidenced by increased Actinobacteria phylum and genera Blautia, Gemella and Phascolarctobacterium, and decreased genera AF12 and Oscillospira. Additionally, global metabolomics analysis identified 26 differential serum metabolites to distinguish PBDE-47 from controls, which were mainly involved in amino acid, lipid, carbohydrate and energy metabolism, further confirmed by pathway analysis. Importantly, the differential serum metabolites are closely correlated with the disturbed gut microbiota in response to PBDE-47. Collectively, our results suggest that maternal gut microbial dysbiosis may serve as a potential mechanism underlying PBDE-47-elicited health hazards to mothers or even offspring.

Environmental impact on reproductive health and risk mitigating strategies.

The purpose of this review is to increase awareness among reproductive health professionals and trainees about the impact of environmental toxicants and climate change on women's health and mitigation strategies at the individual, professional and governmental levels. Global health indicators reveal a meteoric rise of noncommunicable diseases over the past 50 years, which threaten reproductive health directly and indirectly. Evolutionary genetic mutations as contributors are unlikely in this timeframe, and environmental causes have been invoked. Notably, the past 75 years have witnessed marked increases in industrial chemical production, and global warming has rendered a 'climate crisis' with extreme temperatures and compromised food, water, and air quality. There is now strong experimental and epidemiologic evidence for endocrine disrupting chemicals and particulate matter and chemical components of air pollution in the pathophysiology of human reproductive disorders during development and across the lifespan, especially among vulnerable populations. Environmental impacts on fertility, pregnancy outcomes, childhood neurodevelopment, and reproductive tract development are significant, not widely appreciated, and may be preventable. In light of the evidence, education and advocating economical mitigations of toxic environmental chemicals and alternative energy strategies are imperatives to assure quality reproductive health for this and future generations.

Altered functional activations of prefrontal brain areas during emotional processing of fear in Inuit adolescents exposed to environmental contaminants

Exposure to mercury, lead and polychlorinated biphenyls (PCBs) have been associated with emotional dysregulation, but their neuronal correlates have yet to be examined. Inuit from Nunavik (Northern Quebec, Canada) face internalizing problems and are among the most exposed individuals to these environmental contaminants in the world. The aim of this study was to examine the link between pre- and postnatal exposure to these contaminants and brain fear-circuitry in Inuit adolescents. Facial expression stimuli were presented to participants (mean age = 18.3 years) in a magnetic resonance imaging (MRI) scanner. Fear conditioning and extinction tasks included neutral faces as the conditioned threat and safety cues and a fearful face paired with a shrieking scream as the unconditioned stimulus. Functional MRI data were gathered at the conditioning phase (n = 71) and at the extinction phase (n = 62). Mercury, lead and PCB 153 concentrations were measured in blood samples at birth (cord blood) and at the time of the adolescent testing to estimate pre- and postnatal exposure, respectively. For each time point, exposures were categorized in tertiles (low, moderate and high exposed groups). Mixed analyses of variance were conducted for each contaminant of interest controlling for sex, age, socioeconomic status, drug/alcohol use, food insecurity and contaminant co-exposure. Results revealed greater differential activation during the conditioning phase in the right orbitofrontal cortex in participants with moderate and high concentrations of cord blood PCB 153 compared to those in the low exposure group. During the extinction phase, the high prenatal mercury exposed group showed a lower differential activation in the right and left anterior cingulate cortex compared to those in the low-exposed group; whereas there was a higher differential activation in right dorsolateral prefrontal cortex in the high postnatal lead exposed group compared to the moderate- and low-exposed groups. Our study is the first to show alterations in the prefrontal brain areas in fear conditioning and extinction tasks in relation to environmental contaminant exposures. The observed brain correlates may advance our understanding of the emotional problems associated with environmental chemical toxicity.