Endocrine Disruptors Research Articles

A FRET-based competitive binding assay using coumestrol and the ligand-binding domain of human estrogen receptor alpha tagged with mTurquoise2 efficiently expressed in E. coli with ethanol.

The estrogen receptor (ER) is a nuclear receptor and one of the most extensively researched targets in the study of endocrine-disrupting chemicals (EDCs). Many biosensors and bioassays for estrogenic EDCs use the ligand-binding domain of human ERα (LBD-hERα) as a biological recognition element. However, the LBD-hERα is poorly stable and difficult to produce as a functional LBD-hERα in the E. coli expression system. In this study, we efficiently expressed the functional LBD-hERα tagged with the cyan fluorescent protein, mTurquoise2 (LBD-hERα-mTq2) by the addition of ethanol (3%) to E. coli suspension during protein expression (> 40 times more compared to without ethanol). We found that ethanol not only promoted the proper folding of LBD-hERα-mTq2, but also prevented the proteolysis of poorly folded recombinant proteins. We established a FRET-based binding assay between a fluorescent estrogen, coumestrol, and the LBD-hERα-mTq2, in which the formation of the complex exhibits a significant degree of FRET. A subsequent competitive binding assay with diethylstilbestrol demonstrates that our system successfully functions as a simple and reliable bioassay to detect estrogenic EDCs.

Impact of the new hazard classes in the CLP regulation on EU chemicals legislation

The EU recently introduced four new hazard classes to the Classification, Labelling and Packaging Regulation (CLP) (EC) 1272/2008. The classes are endocrine disruption for human health (ED HH) and the environment (ED ENV), persistent, bioaccumulative and toxic (PBT) or very persistent and very bioaccumulative (vPvB), and persistent, mobile and toxic (PMT) or very persistent and very mobile (vPvM). This action was a direct consequence of the EU’s Chemicals Strategy for Sustainability, which aims at strengthening the protection of human health and the environment, as well as reinforcing the CLP Regulation as the central piece of the chemicals legislation. This study examined the regulatory obligations triggered by these new hazard classes, as well as the existing obligations for endocrine disrupters and PBT/vPvB substances identified in other EU regulations. In addition, we compared the CLP criteria for endocrine disruption and PBT/vPvB to criteria existing in other EU regulations and investigated how these criteria are used in the EU chemicals legislation. We found that the implementation of the new hazard classes under the CLP into existing EU chemicals legislation will require the revision of all regulations that rely on the CLP hazard criteria for risk management. Without revision, the immediate impact of the new hazard classes will only extend to six regulations and the regulatory obligations they contain, all of which apply to substances classified under any of the CLP hazard classes. Meanwhile, substances with endocrine disrupting and PBT/vPvB properties are already being identified and regulated using criteria from regulations other than the CLP. When comparing the criteria for identification of endocrine disrupters and PBT/vPvB substances across the chemicals legislation, we found that the criteria differed between regulations. The findings aim to support the efficient implementation of the new CLP hazard classes and harmonization of criteria across regulations, in line with the Chemicals Strategy for Sustainability.

Review of pretreatment and analytical methods for environmental endocrine disruptors: Phthalates.

Phthalates, known as phthalate esters (PAEs), are among the most ubiquitous pervasive env7ironmental endocrine disruptors (EEDs), extensively utilized globally in various facets of modern life due to their irreplaceable role as plasticizers. The exponential production and utilization of plastic goods have substantially escalated plastic waste accumulation. Consequently, PAEs have infiltrated the environment, contaminating food and drinking water reservoirs, posing notable threats to human health. This review provides a comprehensive overview of research advancements in PAE detection and identifies key focal points from 2000 to 2022, utilizing the Web of Science Core Collection. Sample pretreatment and analytical methodologies for PAEs are examined based on bibliometric analysis findings. Pretreatment methods mainly include dispersive solid-phase extraction (DSPE), magnetic solid-phase extraction (MSPE), molecularly imprinted solid-phase extraction (MISPE) and solid-phase microextraction (SPME). Laboratory analytical methods such as gas chromatography (GC), liquid chromatograph (LC) and immunoassay have been described. Additionally, a discussion on the advantages and challenges of rapid on-site detection methods, in comparison to traditional approaches, is presented in alignment with the evolving demands of PAEs detection. Based on the current research progress, future studies can focus on the demand of rapid detection of PAEs.

Endocrine-Disrupting Chemicals and Female Reproductive Aging.

Female reproductive aging often affects women's emotional, physical, and physiological well-being. Ovarian aging is characterized by fluctuations in reproductive hormones and determines the age at which menopause occurs. Understanding potentially modifiable factors that influence this process is essential for addressing health disparities, improving quality of life, and informing relevant public health strategies. This review synthesizes in vivo, in vitro, and epidemiological findings about the effects of endocrine-disrupting chemicals (EDCs), specifically heavy metals and perfluoroalkyl and polyfluoroalkyl substances (PFAS) on female reproductive aging. Most in vivo and in vitro studies have demonstrated that heavy metals alter ovarian morphology, folliculogenesis, and steroidogenesis. Evidence regarding the effects of PFAS is limited and inconsistent. Epidemiological studies have consistently shown that heavy metals are associated with a higher risk of diminished ovarian reserve (indicated by decreased anti-Müllerian hormone) and earlier menopause, with limited findings regarding reproductive hormone changes. PFAS exposure has been associated with decreased estradiol and earlier menopause but not significantly with ovarian reserve. Gaps in the literature require more comprehensive epidemiological research on the effects of EDCs on female reproductive aging, including ovarian reserve, age at menopause, and vasomotor symptoms, to inform future interventions to reduce hazardous exposures and improve women's health.

Dioxins and their impact: a review of toxicity, persistence, and novel remediation strategies.

Dioxins rank among the most hazardous persistent organic pollutants, presenting a serious threat due to their long environmental lifespan and capacity for bioaccumulation. This comprehensive review delves into the historical, chemical, and toxicological aspects of dioxins, spotlighting significant incidents such as the Seveso disaster and the repercussions of Agent Orange. The review offers a thorough analysis of the sources of dioxin formation, encompassing natural occurrences like volcanic eruptions and wildfires, alongside man-made activities such as industrial combustion and waste incineration. It examines regional variations in dioxin contamination, revealing air concentrations that can range from less than 0.01 pg TEQ per m3 in remote regions to as high as 2 pg TEQ per m3 in urban environments. With global dioxin emissions estimated at around 97.0 kg TEQ per year, Asia and Africa emerge as the highest emitters among the continents, with the total global dioxin release approximately at 100.4 kg TEQ annually. Dioxin emissions per capita show stark contrasts across six continents, from 10.77 g TEQ per capita in Europe to a concerning 71.66 g TEQ per capita in Oceania. Furthermore, the concentration of dioxin compounds produced during combustion varies significantly, ranging from 15 to 555 ng m-2. While dioxin emission regulations are intricate and differ globally, most nations require that concentrations remain below one ng m-2. Globally, dioxin production is estimated at 17 226 kilograms annually, equating to about 287 kilograms in toxic equivalent (TEQ). This review critically examines the severe health implications of dioxins, which include carcinogenic effects, endocrine disruption, and immunotoxicity. Innovative remediation strategies, such as using nanomaterials for adsorption and advanced oxidation processes, are identified as promising pathways to tackle this pressing issue. Ultimately, this review underscores the necessity for enhanced monitoring systems and comprehensive policy frameworks to facilitate sustainable dioxin management and regulatory compliance. Taking decisive action is vital to protect public health and the environment from the ongoing threat posed by dioxins.

Next Generation Risk Assessment to Address Disease-Related Vulnerability—A Proof of Concept for the Sunscreen Octocrylene

Risk assessment for cosmetics in the European Union (EU) are triggered by a ban on animal testing and concerns of endocrine disruption (ED). The risk assessment focuses on healthy populations and, for potential ED, includes specific developmental stages as vulnerable due to specific concerns on endocrine effects. However, the assessment focuses on healthy individuals and does not consider that some pathologies may increase dermal absorption and even vulnerability to endocrine disruptors. Data from the EU risk assessment, human pharmacokinetic studies and ToxCast bioactivity were combined in a hypothesis-driven Next-Generation Risk Assessment to identify possible risk drivers for vulnerable populations including oncological patients and atopic dermatitis. In vitro effects are observed at concentration in the order of measured plasmatic levels under normal use patterns. The induction of hepatic enzymes is the most relevant bioactivity endpoint, in line with animal findings. The information on endocrine potential is inconclusive, and the possibility for skin effects and endocrine mechanism linked to tumor induction require further elucidation. The information on octocrylene (CAS number: 6197-30-4) bioactivity is limited, lacking information on the metabolites and the immunotoxicity potential, particularly relevant for oncological patients.

Contamination Characterization, Toxicological Properties, and Health Risk Assessment of Bisphenols in Multiple Media: Current Research Status and Future Perspectives

Bisphenols (BPs) are ubiquitous environmental endocrine disruptors that cause various human health hazards and pollute water, soil, and the atmosphere to varying degrees. Although various studies have investigated the pollution characteristics and health hazards of BPs in different media, a systematic review of BPs in the broader environmental context is still lacking. This study highlights the pollution characteristics, detection methods, and risk assessment status of BPs by combining relevant studies from both domestic and international sources, and their environmental distribution characteristics are summarized. The results show that BP pollution is a widespread and complex global phenomenon. Bisphenol A (BPA) remains the predominant component of BPs, which can damage the nervous and reproductive systems. At present, high-performance liquid chromatography–tandem mass spectrometry, high-performance liquid chromatography, and liquid chromatography–tandem mass spectrometry are the main detection methods used for BPs. BPs can also damage the reproductive system, leading to germ cell apoptosis and ovarian damage. Future research should focus on expanding the BP testing repertoire, advancing rapid detection techniques, elucidating toxic mechanisms, conducting comprehensive safety assessments, and developing systematic health risk assessment methods. These efforts will provide a scientific foundation for preventing and controlling emerging pollutants.

Editorial: Thyroid endocrine disruptors

Editorial: Thyroid endocrine disruptors

Thyroid Endocrine Disrupting Potential of Fluoxetine in Zebrafish Larvae.

Fluoxetine (FLX), a typical selective serotonin reuptake inhibitors, has been frequently detected in aquatic environment and wild fish. However, little is known about its effect on thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to 1, 3, 10, and 30 μg/L of FLX for 6 days. Chemical analysis demonstrated that FLX and its metabolic product (nonfluoxetine, NFLX) were accumulated in zebrafish larvae. The exposure resulted in decreased thyroid hormones (THs) levels, indicating thyroid endocrine disruption. Moreover, thyroid-stimulating hormone (TSH) content was significantly inhibited in a concentration-dependent manner after exposure to FLX. Gene transcription in the hypothalamic-pituitary-thyroid (HPT) axis was further examined, and the results showed that the genes encoding corticotrophin-releasing hormone (crh) and thyrotropin-releasing hormone (trh) were significantly up-regulated as a compensatory mechanism for the decreased TH contents accompanied with decreased tshβ mRNA expression. In addition, genes involved in thyroid hormone synthesis (sodium/iodide symporter, nis, thyroglobulin, tg) and transport (transthyretin, ttr) were down-regulated after exposure to FLX in a concentration-dependent manner. The increased gene transcription of deiodinases (dio2) and uridinediphosphate-glucuronosyltransferase (ugt1ab) might be responsible for the decrease of TH contents. In addition, a significant inhibition in thyroid hormone receptors (trα and trβ) gene expression was observed upon treatment with FLX. All these results demonstrated that FLX could alter THs and TSH content as well as gene transcription in the HPT axis, exerting an endocrine disruption of the thyroid system in zebrafish larvae.

Validating the Black Identity, Hair Product Use, and Breast Cancer Scale (BHBS) Among Black Breast Cancer Survivors

Personal care products containing toxic chemicals (e.g., endocrine-disrupting chemicals) may increase breast cancer risk, especially for Black women who use these products more than other racial groups. There are limited tools that examine the intersections of identity, behaviors, and attitudes surrounding product use, perceived safety, and breast cancer risk; thus, the Black Identity, Hair Product Use, and Breast Cancer Scale (BHBS) was developed to bridge this gap. While initial validations lacked diverse survivor representation, this study seeks to validate the BHBS among Black survivors. Methods: This study is a part of the Bench to Community Initiative (BCI), where respondents (n = 167) completed a 41-item survey including the BHBS between 2020 and 2022. The use of Principal Component Analysis (PCA) and confirmatory factor analysis (CFA) established the underlying component structures and model fit. CFA measures used to confirm component structures included the Root Mean Square Error of Approximation, the Comparative Fit Index, and the Tucker Lewis Index. Results: Black survivors on average were diagnosed with breast cancer before age 40 (37.41 ± 8.8) with Stage 1 (45%) disease. Sixty-three percent of the total variance resulted in a two-component structure. Subscale 1 (S1) measures the sociocultural perspectives about hair and identity (28% of the total variance; α = 0.73; 95% CI = 0.71–0.82). Subscale 2 (S2) can be used to assess perceived breast cancer risk related to hair product use (35% of the total variance; α = 0.86; 95% CI = 0.81–0.94). The two-component structure was confirmed with Root Mean Square Error of Approximation = 0.034, Comparative Fit Index = 0.93, and Tucker Lewis Index = 0.89. Discussion/Conclusions: The BHBS is a valid tool to measure identity, attitudes, and behaviors about product use and breast cancer risk among survivors. Hair is a significant cultural identity expression, and the health effects of styling products should be considered in future interventions.

Toxic Alerts of Endocrine Disruption Revealed by Explainable Artificial Intelligence

Toxic Alerts of Endocrine Disruption Revealed by Explainable Artificial Intelligence

Microplastics influencing aquatic environment and human health: A review of source, determination, distribution, removal, degradation, management strategy and future perspective.

Microplastics (MPs) are produced from various primary and secondary sources and pose multifaceted environmental problems. They are of non-biodegradable nature and may stay in aquatic environments for a long time period. The present review has covered novel aspects pertaining to MPs that were not covered in earlier studies. It has been observed that several methods are being employed for samples collection, extraction and identification of MPs and polymer types using various equipment, chemicals and instrumental techniques. Aquatic species mistakenly ingest MPs, considering them prey and through food-chain, and then suffer from various metabolic disorders. The consumption of seafood and fish may consequently cause health implications in humans. Certain plasticizers are added during manufacturing to provide colour, durability, flexibility, and strength to plastics, but they leach out during usage, storage, and transport, as well as after entering the bodies of aquatic species and human beings. The leached chemicals (bisphenol-A, triclosan, phthalates, etc.) act as endocrine disrupting chemicals (EDCs), which effect on homeostasis; thereby causing neurotoxicity, cytotoxicity, reproductive problems, adverse behaviour and autism. Negative influence of MPs on carbon sequestration potential of water bodies is also observed, however more studies are required to understand it with a detail mechanism under natural conditions. The wastewater treatment plants are found to remove a large amount of MPs, but in turn, also act as significant sources of their release in sludge and effluents. Further, it is covered that how advanced oxidation processes, thermal- and photo-oxidation, fungi, algae and microbes degrade the plastics and increase their numbers in the surrounding environment. The management strategy comprising recovery of energy and other valuable by-products from plastic wastes, recycling and regulatory framework; are also described in detail. The future perspectives can be of paramount importance to control MPs generation and their abundance in the aquatic and other types of environments. The studies in future need to focus on advanced filtration techniques, advanced oxidation processes, energy recovery from plastic wastes and influences of MPs on carbon sequestration in aquatic environment and human health.

Pivotal Role of Multishelled Architecture in Nanoreactor with Spatial Confined Co3O4 for Peroxymonosulfate Activation and Contaminants Degradation

In recent years, cobalt‐based catalysts have been widely used in advanced oxidation technology to degrade pollutants in water environments. However, the reasons for the improved efficiency and performance of cobalt‐based catalysts with different shapes and structures on the activation of persulfate for contaminant degradation are still largely unknown. This study constructs different shapes and structures of cobalt‐based catalysts, namely, Co3O4 nanosphere, multishelled Co3O4 nanosphere (MSCONS), Co3O4 nanocube and multishelled Co3O4 nanocube, in combination with persulfate activation, on the degradation of tetracycline (TC) and bisphenol A (BPA), representative substances of antibiotics and endocrine disruptors in water environments. Batch experiments exhibit satisfactory TC (96.3%) and BPA (98.5%) degradation efficiency under MSCONS/peroxymonosulfate. Furthermore, MSCONS exhibits wide applicability under complex water matrix conditions. Consequently, an integration of density functional theory computations and intermediates analysis demonstrates that the synergy, rather than the isolated effects of radical and nonradical active species, broadens the degradation pathways of TC and BPA, thereby improving the removal efficiency. Overall, this study offers novel insights into the factors contributing to the enhanced performance of cobalt‐based catalysts with varying shapes and structures. Additionally, it proposes new research avenues for investigating the effects of shapes and structures on other transition metal‐based catalysts.

Bisphenol F (BPF) exposure impairs sperm quality and offspring development in male zebrafish.

Bisphenol F (BPF), a substitute for bisphenol A (BPA), is widely used in consumer products, increasing the potential for environmental exposure. Our study investigated the reproductive effects of BPF on adult male zebrafish and explored its toxicological mechanisms, as well as its intergenerational effects. Adult male zebrafish were exposed to BPF concentrations of 0, 50, 500, 2500, and 5000 nM for 21 days. We evaluated sperm cell quantity and quality, hormonal markers testosterone (T) and vitellogenin (VTG), gene expression profiles related to hormone synthesis, metabolism, apoptosis, cell cycle, sexual behavior, and offspring health metrics including survival, development and locomotion. BPF exposure did not significantly affect body weight or gonadal index. However, at 500 and 2500 nM, a significant reduction in sperm count was observed. BPF exposure led to decreased serum T and increased hepatic VTG levels, indicating hormonal disruption. At 50 nM, BPF initiated sperm apoptosis, and at higher doses, it disrupted sperm meiosis, affecting cell distribution. This exposure negatively impacted sperm quality, reduced offspring survival rates, and altered sperm motility in adult fish. Offspring from BPF-exposed groups showed developmental issues, including increased mortality, delayed developmental stages, abnormal tail coiling and heart rate, which correlated with paternal sperm count and quality changes, alterations in T and VTG levels, and cell cycle phase distributions. Our study demonstrated that BPF exposure significantly impacted sperm quality, characterized by reduced sperm count and altered motility patterns, leading to developmental anomalies in offspring. These novel findings highlight the need for further research into BPF's reproductive and developmental toxicity, emphasizing the potential risks to aquatic ecosystems and human health. The observed effects on sperm quality, hormonal balance, and offspring development provide new insights into the reproductive toxicity profile of BPF.

Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns

BackgroundGestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.MethodsThis study included 75 pregnant individuals who delivered at the University of Cincinnati Hospital from 2014 to 2017. We measured maternal urinary biomarkers of paraben/phenol (12), phthalate (13), and phthalate replacements (4) from the samples collected during the delivery visit. Global serum metabolome profiles were analyzed from maternal blood (n = 72) and newborn (n = 63) cord blood samples collected at delivery. Fifteen of the 29 urinary biomarkers were excluded due to low detection frequency or potential exposures during hospital stay. We assessed metabolome-wide associations between 14 maternal urinary biomarkers and maternal/newborn metabolome profiles. Additionally, performed enrichment analysis to identify potential alterations in metabolic pathways.ResultsWe observed metabolome-wide associations between maternal urinary concentrations of phthalate metabolites (mono-isobutyl phthalate), phthalate replacements (mono-2-ethyl-5-carboxypentyl terephthalate, mono-2-ethyl-5-hydroxyhexyl terephthalate) and phenols (bisphenol-A, bisphenol-S) and maternal serum metabolome, using q-value < 0.2 as a threshold. Additionally, associations of phthalate metabolites (mono-n-butyl phthalate, monobenzyl phthalate) and phenols (2,5-dichlorophenol, BPA) with the newborn metabolome were noted. Enrichment analyses revealed associations (p-gamma < 0.05) with amino acid, carbohydrate, lipid, glycan, vitamin, and other cofactor metabolism pathways.ConclusionMaternal paraben, phenol, phthalate, and phthalate replacement biomarker concentrations at delivery were associated with maternal and newborn serum global metabolome.

Green Chemistry Method for Analyzing Bisphenol A in Milk

A simple, fast, green, and sensitive method for determining Bisphenol A (BPA) levels in commercial milk was developed using a solventless sample preparation technique known as stir bar sorptive extraction, coupled with thermal desorption–gas chromatography/mass spectrometry. BPA was selected due to its ubiquitous presence in the environment and its classification as an endocrine-disrupting chemical of concern (i.e., its ability to mimic hormone functions). Studies have reported that BPA can leach into various food sources, including milk, a dietary staple for infants. It is critical to have an effective and efficient process for monitoring the presence of BPA in milk to protect children’s health. Current detection methods for BPA in milk are lengthy and tedious and tend to require the use of organic solvents for the extraction of BPA. This optimized “green” method provides an effective alternative for BPA detection in a challenging matrix, e.g., milk. Factors such as pH (1.5, 6, and 13), temperature (70–80 °C), and sonication (1 h, 2 h, and 3 h) were studied with a BPA-spiked whole milk sample (final concentration of 8 ppb) to optimize the extraction efficiency without the use of solvents. The developed methodology improves BPA recovery from whole milk by over 50%, with a detection limit in the parts per trillion range (45 ng/L). The sample preparation developed in this report rendered a more sensitive option for analyzing BPA in milk, with a limit of detection in the parts per trillion range (compared to low ppb) even though the recovery performance is not as good as in reported studies (54% vs. &gt;85%); nonetheless, it provides a green alternative for future studies assessing BPA exposure through dairy products.

Determination of highly hazardous pesticides in fruits and vegetables in the Maya region of southeast of Mexico

Highly Hazardous Pesticides (HHPs) have been identified as substances with severe adverse effects, including carcinogenicity, endocrine disruption, and reproductive toxicity. The aim of this study was to evaluate pesticide residues in fruits and vegetables from Hopelchén to provide evidence for policy recommendations on pesticide regulation. A total of 25 samples were collected and analyzed using the QuEChERS method with GC-MS/MS and LC-MS techniques. Of the 156 pesticides screened, 25 were detected, with tebuconazole, chlorantraniliprole, imidacloprid and carbendazim among the most frequent. Approximately 20% of the pesticides identified qualified as HHPs based on WHO/FAO criteria, while 60% were categorized as HHPs according to the more comprehensive criteria outlined by Pesticide Action Network International. Many of these pesticides exhibited toxicity to bees and high environmental persistence. Furthermore, 33% of the samples exceeded the European Union’s Maximum Residue Limits, particularly for pesticides in papayas and bell peppers. Our findings show the presence of HHPs in the region, which represent critical hazards to ecosystem, pollinator populations, and public health. This work may contribute to the development of specific HHPs classification criteria for Mexico, thus advancing the transition toward safer, with special emphasis on vulnerable regions such as the Mayan zone in southeastern Mexico.

Ne Health: Bisphenol a and Early Puberty, a Systematic Literature Review

Objective: Investigate the relationship between BPA exposure and precocious puberty. Theoretical Framework: The theoretical framework includes studies that aim to demonstrate human contamination by BPA; highlight its toxic potential to human health and the environment; and associate BPA exposure with alterations in pubertal development (Valadares and Pfeilsticker, 2012; Castro-Correia and Fontoura, 2015; Sonnenschein and Soto, 2010, among others). Method: The methodology adopted for this research comprises a systematic literature review, analyzing experimental, epidemiological, and clinical studies available in databases such as PubMed, Scopus, and Web of Science. Results and Discussion: The results revealed a positive correlation between BPA exposure and alterations in pubertal development, particularly in girls, with evidence pointing to the influence of this compound in accelerating sexual maturation. However, the methodological heterogeneity of the studies and the lack of consensus on the exact biological mechanisms indicate the need for more robust research. Research Implications: This study contributes to the literature by demonstrating that BPA exposure may be a risk factor for precocious puberty, highlighting the importance of stricter regulatory policies and additional investigations to confirm and clarify this association. Originality/Value: This study significantly contributes to the literature by gathering and synthesizing available evidence on the relationship between bisphenol A (BPA) exposure and precocious puberty. It provides a comprehensive overview of the experimental, epidemiological, and clinical data, highlighting the potential of BPA as an environmental risk factor for alterations in pubertal development, particularly in girls.Furthermore, the article identifies critical gaps in scientific knowledge, such as the lack of consensus on the exact biological mechanisms through which BPA accelerates sexual maturation and the methodological heterogeneity present in the analyzed studies. This critical approach reinforces the need for future research that is more robust and methodologically consistent. Finally, by emphasizing the importance of stricter regulatory policies to minimize BPA exposure, the study also contributes to a public health agenda, pointing to pathways for interventions that can mitigate the impacts of this endocrine disruptor on human health and the environment.

Maternal exposure to bisphenol A induces congenital heart disease through mitochondrial dysfunction.

Congenital heart disease (CHD) represents a major birth defect associated with substantial morbidity and mortality. Although environmental factors are acknowledged as potential contributors to CHD, the underlying mechanisms remain poorly understood. Bisphenol A (BPA), a common endocrine disruptor, has attracted significant attention due to its widespread use and associated health risks. This study examined the effects of maternal BPA exposure on fetal heart development in a murine model. The findings indicated that high-dose BPA exposure resulted in fetal growth restriction, myocardial wall thinning, and ventricular septal defects. Transcriptomic analysis revealed downregulation of genes associated with mitochondrial energy synthesis and cardiomyocyte development following high-dose BPA exposure. Functional assays demonstrated that high-dose BPA exposure impaired mitochondrial respiration reduced ATP production, disrupted mitochondrial membrane potential, and increased intracellular reactive oxygen species levels in fetal cardiomyocytes. These results elucidate the detrimental effects of BPA on fetal heart development and mitochondrial function, providing insights into potential mechanisms linking environmental chemical exposure to CHD.

Deciphering the phenotypic, inflammatory, and endocrine disrupting impacts of e-waste plastic-associated chemicals.

As the volume of plastic waste from electrical and electronic equipment (WEEE) continues to rise, a significant portion is disposed of in the environment, with only a small fraction being recycled. Both disposal and recycling pose unknown health risks that require immediate attention. Existing knowledge of WEEE plastic toxicity is limited and mostly relies on epidemiological data and association studies, with few insights into the underlying toxicity mechanisms. Therefore, this study aimed to perform comprehensive chemical screening and mechanistic toxicological assessment of WEEE plastic-associated chemicals. Chemical analysis, utilizing suspect screening based on high-resolution mass spectrometry, along with quantitative target chemical analysis, unveiled numerous hazardous compounds including polyaromatic compounds, organophosphate flame retardants, phthalates, benzotriazoles, etc. Toxicity endpoints included perturbation of morphological phenotypes using the Cell Painting approach, inflammatory response, oxidative stress, and endocrine disruption. Results demonstrated that WEEE plastic chemicals altered the phenotypes of the cytoskeleton, endoplasmic reticulum, and mitochondria in a dose-dependent manner. In addition, WEEE chemicals induced inflammatory responses in resting macrophages and altered inflammatory responses in lipopolysaccharide-primed macrophages. Furthermore, WEEE chemicals activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, indicating oxidative stress, and the aryl hydrocarbon receptor (AhR). Endocrine disruption was also observed through the activation of estrogenic receptor-α (ER-α) and the induction of anti-androgenic activity. The findings show that WEEE plastic-associated chemicals exert effects in multiple subcellular sites, via different receptors and mechanisms. Thus, an integrated approach employing both chemical and toxicological methods is essential for comprehensive assessment of the toxicity mechanisms and cumulative chemical burden of WEEE plastic-associated chemicals.