Search Results (858)

Human fertility is declining across industrialised populations, while the incidence of hormone-dependent reproductive cancers rises. Endocrine-disrupting chemicals (EDCs) and structurally related emerging pollutants are implicated in both. These two outcomes are generally reviewed as separate studies. This review argues that they are two latencies of a single molecular toxicology. The compounds concerned are structurally diverse: phthalates, bisphenols, per- and polyfluoroalkyl substances (PFASs), pesticides, polychlorinated biphenyls (PCBs) and dioxins, brominated and organophosphate flame retardants, pharmaceuticals and personal-care products (PPCPs), and micro- and nanoplastics. They nonetheless converge on a limited repertoire of molecular lesions. These include the disruption of hypothalamic–pituitary–gonadal (HPG) signalling through kisspeptin/GnRH and gonadotropin gene expression and interference at nuclear and membrane hormone receptors (ERα/β, AR, GPER, thyroid receptors, AhR, PPARγ). They also include the inhibition of steroidogenesis at StAR and the CYP11A1–CYP17A1–CYP19A1/3β-HSD/17β-HSD cascade and reactive-oxygen-species generation with mitochondrial dysfunction and Keap1–Nrf2 disruption. Epigenetic reprogramming through DNA methylation, histone modification and non-coding RNAs, together with crosstalk with metabolic and immune signalling, completes the set. These lesions produce measurable cytotoxic and genotoxic damage to gametes and the early embryo: sperm DNA fragmentation and 8-oxo-dG accumulation, blood–testis-barrier breakdown, oocyte meiotic-spindle defects, and granulosa-cell apoptosis and pyroptosis. The same receptor, oxidative and genotoxic hubs drive hormone-dependent reproductive carcinogenesis over longer latencies. The review makes three contributions. First, it traces these shared hubs continuously from fertility impairment to malignancy rather than treating them as separate fields. Second, it grades the certainty of the human evidence class by class, so that robust associations can be distinguished from provisional ones. Third, it integrates pseudo-persistent pollutants alongside the classical persistent compounds. These are micro- and nanoplastics, which act as both toxicants and vectors for adsorbed co-contaminants, and pharmaceutical and personal-care residues sustained by continuous wastewater input. Their inclusion demonstrates that chronic low-dose exposure does not require chemical persistence. We conclude with mitigation strategies and an explicit account of what the current evidence base cannot yet support. Full article

Autism spectrum disorder (ASD) risk reflects genetic susceptibility and modifiable environmental exposures acting during fetal and early postnatal critical periods. Building on our prior two-path model, in which folate receptor autoantibody-driven cerebral folate deficiency and oxidative stress/neuroinflammation converge on disrupted neurodevelopment, this review provides the first full mechanistic treatment of environmental pollutants within that framework. We synthesize evidence across seven exposure categories: micro/nanoplastics, plastic-associated endocrine-disrupting chemicals, ambient/indoor air pollution, tire wear particles and 6PPD-quinone, heavy metals and pesticides, industrial chemicals and persistent organic pollutants, and ultra-processed food intake as a parallel, non-pollutant contributor to the same inflammatory pathway. Human biomonitoring of micro/nanoplastics has progressed beyond detection in the placenta, brain and breast milk to direct evidence of placental genotoxicity and fetal endocrine disruption, complementing rodent data linking early-life exposure to impaired corticogenesis, disrupted microglial synaptic pruning, and ASD-relevant behavioral deficits. Across categories, oxidative stress, barrier disruption, neuroinflammation, endocrine disruption, and epigenetic modification recur as convergent mechanisms acting on trimester- and age-specific windows of vulnerability. Genetic variation in folate pathway and mitochondrial genes, as well as folate/vitamin B sufficiency, are proposed as candidate effect modifiers rather than established protective factors to modify susceptibility to this pollutant burden. Most evidence is associational or mechanistic rather than trial-based; we grade evidence strength and translate findings into biomarker-guided clinical and population-level policy guidance. Full article

Background/Objectives: Pregnant women are vulnerable to endocrine-disrupting chemicals such as bisphenol A (BPA). However, associations of maternal BPA exposure with oxidative stress, inflammation, the Dietary Inflammatory Index (DII), dietary total antioxidant capacity (DTAC), and fetal/neonatal outcomes remain unclear. This study evaluated urinary and estimated dietary BPA exposure in conjunction with DII and DTAC during late pregnancy and examined their associations with maternal oxidative stress and inflammatory biomarkers and fetal/neonatal outcomes. Methods: This cross-sectional study included 86 third-trimester pregnant women at a Turkish tertiary hospital. BPA exposure was assessed using creatinine-adjusted urinary BPA concentrations and dietary intake estimated from 3-day dietary records and a food frequency questionnaire. Urinary and serum biomarkers were measured, and DII and DTAC scores calculated. Analyses included correlation, multivariable regression, and mediation. Results: Creatinine-adjusted urinary BPA correlated strongly with urinary 8-isoprostane (r = 0.694, p < 0.001) and 8-hydroxy-2′-deoxyguanosine (8-OHdG; r = 0.880, p < 0.001), but not after multivariable adjustment. Neither urinary nor dietary BPA exposure showed consistent adjusted associations with serum oxidative stress or inflammatory biomarkers or significant associations with fetal/neonatal outcomes. DII and DTAC correlated with selected inflammatory biomarkers, particularly TNF-α. Dietary BPA hazard quotients exceeded 1 using EFSA’s updated 2023 tolerable daily intake, suggesting a potential health concern. Conclusions: Urinary BPA correlated strongly with urinary oxidative damage biomarkers, but not after multivariable adjustment. Neither urinary nor dietary BPA showed consistent adjusted associations with maternal oxidative stress or inflammatory biomarkers or significant associations with fetal/neonatal outcomes. DII and DTAC may be related to inflammatory biomarker variability in late pregnancy. Full article

Three-dimensional (3D) printing and bioprinting technologies are increasingly used in tissue engineering and in the development of personalized medical devices with tailored biological and mechanical properties. Despite their advantages, these technologies may involve exposure to chemical compounds with uncertain biological effects, including potential endocrine-disrupting activity. This study aims to evaluate the hormonal activity and cytotoxicity of various materials commonly used for 3D printing technologies, including thermoplastics and synthetic materials (PLA, ABS, PCL, b-TPUe, PVA, PEGDA), and biomaterials (collagen, alginate, hyaluronic acid, agarose, silk fibroin, GelMA, HAMA). Hormonal activity was evaluated using the E-screen assay for estrogenic and anti-estrogenic activity, and the PALM assay for androgenic and anti-androgenic activity. Cytotoxic effects are evaluated by assessing cellular metabolic viability using the MTT assay. No detectable estrogenic, anti-estrogenic, androgenic, or anti-androgenic activity, nor any signs of cytotoxicity, were observed within the experimental conditions analysed. This study represents the first analysis of some specific endocrine-related endpoints of a wide range of 3D printing and bioprinting materials, and should not be interpreted as definitive proof of the complete absence of endocrine activity. Further studies addressing additional toxicological parameters and long-term assessments are required to comprehensively characterize their safety and suitability. Full article

Nonylphenol (NP) is a chemical compound belonging to the class of alkylphenols (APs), known for its widespread environmental distribution and endocrine-disrupting properties. It is commonly used in the production of detergents, pesticides, and plastic materials and, owing to these properties, it can accumulate in both aquatic and terrestrial ecosystems. As a xenoestrogenic compound, NP can bind steroid receptors, including estrogen receptors (ERs), thereby activating ER-dependent pathways. In this work, we investigated the effects of NP alone and in combination with the endogenous hormones 17β-oestradiol (E2) and/or testosterone (T) on a human non-tumoral prostate cell line (PNT1A). Cell viability and migration assays, together with analysis of ER expression and localization, were carried out to assess the xenoestrogenic activity of NP, particularly in the presence of E2 and T. Our results showed that NP retained its endocrine-disrupting features in the mixtures, positively affecting cell viability, except for the NP+E2 mixture, in which cell viability did not significantly differ from control, suggesting an antagonistic interaction between NP and E2. The mixtures also interfered with steroid receptor dynamics, affecting receptor expression and delaying receptor localization and activation kinetics. Moreover, all mixtures negatively affected cell migration compared with treatment with endogenous hormones alone. In conclusion, our results demonstrate that NP retains its xenoestrogenic behavior in mixture, inducing a significant alteration in prostate cell homeostasis. Full article

The personal care product market has expanded rapidly in recent years, along with growing consumer awareness of chemical exposures and increasing demand for “clean” products. Consumer perceptions of product safety and potential health impacts are commonly based on ingredient labels, intended use, and certifications, rather than the full chemical composition of finished products. In this study, we conducted a targeted review of certification and ingredient-evaluation programs in the United States and European markets. Eighteen programs were identified and characterized based on their evaluation approaches, data sources, and whether they incorporate analytical measurement of finished products. We also evaluated the current U.S. and EU regulatory frameworks. Across both certification and regulatory systems, evaluation was found to rely primarily on ingredient-based approaches and supporting documentation, with limited incorporation of analytical measurement. As a result, contaminants, impurities, and incidentals/non-intentionally added substances (which have previously been identified in many consumer products) may not be consistently identified or evaluated for safety. These findings highlight a fundamental gap between intended formulation and actual product composition. Incorporating analytical measurement, particularly non-targeted approaches, provides a complementary groundwork for identifying previously unrecognized chemical exposures and improving the accuracy of product safety certification programs and hazard assessments. Aligning evaluation with measured chemical composition may enhance transparency and better reflect real-world exposure, support more credible sustainability claims, enhance consumer trust, support growing market demand, support consumer safety, and contribute to more effective regulation in the personal care industry. Full article

Atherosclerosis is a complex, multifactorial disease and the leading underlying cause of cardiovascular morbidity and mortality worldwide. Beyond traditional risk factors, growing evidence highlights the critical role of environmental exposures in modulating atherogenesis. In real-world scenarios, individuals are exposed to complex mixtures of contaminants, including particulate matter, toxic metals, pesticides, polycyclic aromatic hydrocarbons, and endocrine-disrupting chemicals. These combined exposures may exert additive, synergistic or antagonistic effects, resulting in biological responses that cannot always be predicted from single-agent exposures. At the cellular and molecular level, both chemical mixtures and environmental co-exposures converge on key pathogenic pathways, including oxidative stress, endothelial dysfunction, chronic inflammation, and lipid dysregulation. These processes may favor monocyte recruitment, foam cell formation, vascular smooth muscle cell remodeling, and plaque instability. Moreover, cumulative exposures are associated with epigenetic alterations, such as dysregulation of DNA methylation and non-coding expression patterns, which may influence long-term susceptibility to atherosclerosis. This structured narrative review synthesizes evidence from 37 studies investigating the cellular and molecular mechanisms underlying the impact of environmental mixtures and multipollutant co-exposures on atherosclerosis. By integrating evidence from epidemiological, toxicological, experimental, bioinformatics and multi-omics studies, while recognizing the predominantly associative nature of the available human evidence, we highlight emerging mechanistic insights and discuss the relevance of mixture-based approaches for improving risk assessment and informing future preventive strategies. Full article

Bisphenol A (BPA) is a non-persistent industrial chemical widely used in the production of polycarbonate plastics and epoxy resins. Due to its mass production and versatility, BPA is ubiquitous in environmental matrices, leading to human exposure through ingestion, dermal contact, and inhalation. As a known endocrine-disrupting chemical (EDC) with estrogenic activity, BPA exposure has been associated with reproductive, metabolic, immune, oncogenic, and developmental effects. Mechanistically, BPA is reported to exert its toxic effects via multiple pathways, including alterations in epigenetic microRNA (miRNA) expression. miRNAs are endogenous non-coding RNA molecules that regulate gene expression by targeting mRNAs, thereby influencing a wide range of cellular and metabolic pathways involved in development and disease. Importantly, this review consolidates evidence suggesting that the biological effects of BPA may, in part, be mediated through miRNA-driven epigenetic modifications, affecting numerous downstream proteins and signaling pathways. Altered miRNA expression induced by BPA exposure is implicated in diverse health outcomes, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental abnormalities. Notably, BPA exposure predominantly results in the upregulation of specific miRNAs, such as miR-21 and miR-146a, although tissue-specific and sex-dependent variations are evident. In this review, we provide a comprehensive overview of human, in vivo, and in vitro studies investigating BPA-induced miRNA dysregulation and its associated biological effects. Full article

Background–Aim: Children represent a particularly susceptible population to endocrine-disrupting chemical (EDC) exposure; however, biomonitoring data in this population remain limited. To the best of our knowledge, this is the first study using hair biomonitoring to simultaneously assess the concentrations of phthalate metabolites (PMs), triclosan (TCS) and triclocarban (TCC) in children with obesity (OB), type 1 diabetes mellitus (T1D), and hypothalamic–pituitary-related diseases (HPRD), through hair biomonitoring. Methods: Liquid chromatography–mass spectrometry (LC-MS) was used to measure TCS, TCC and PM levels in head hair samples from 212 children, categorized into control, T1D, HPRD and OB groups. PMs and TCS levels were compared across groups and evaluated in relation to health issues, cosmetics exposure, dietary habits, cardiometabolic, and somatometric parameters. Results: Our hair biomonitoring results showed that the most commonly detected EDCs were MEHP, MBP, MiBP, and TCS, with detection frequencies of samples 95.3%, 84.4%, 79.7%, and 60.8%, respectively. Children with T1D had statistically significantly higher mean MEHP concentrations than the control group. Children with HPRD exhibited higher PM concentrations, primarily driven by elevated mean MEHP and MBP levels compared with the control group. In contrast, mean MiBP levels were lower in the OB group than in the control group. Regarding TCS levels, no statistically significant differences were observed across the disease groups compared with controls. TCS was inversely associated with somatometric parameters in the OB group. Subgroup analyses by age, sex, residence area, and maternal education were conducted to assess statistically significant differences in concentrations of PM and TCS. Conclusions: Overall, our biomonitoring results indicate group-specific concentration patterns of PMs and TCS among children with T1D, HPRD and OB groups compared to the control group. In particular, PM levels were higher in children with T1D and HPRD and lower in those with OB groups compared to the control group. As a result, this is the first study to assess PM and TCS concentrations in children across clinical groups, using hair matrix. Full article

Numerous types of environmental toxicants alter human metabolomics, directly or indirectly, through gut microbial dysbiosis, upsetting immune homeostasis. Environmental toxicants capable of these direct and indirect effects have included heavy metals, pesticides, herbicides, polychlorinated biphenyl (PCB) congeners, and endocrine-disrupting chemicals. The cell and molecular events induced by some diverse toxicants are reviewed, along with their potential additive, synergistic, and antagonistic effects on immune homeostasis (increasing proinflammatory immune cell activation and suppressing immunoregulation), which leads to systemic oxidative stress (OS). As people are exposed in varying degrees to countless chemicals and environmental factors over a lifetime, it is challenging to correlate specific diagnoses to any single toxicant or exposure, which is often a key challenge in linking environmental exposure to health outcomes. However, many toxicants have the common mechanistic effect of OS. The effects of toxicants are more pronounced with aging due to cumulative exposures and immunoaging (immunosenescence), with chronic low-grade inflammation referred to as “inflammaging”. The cell and molecular mechanisms of toxicants include altered calcium flux, mitochondrial dysfunction, and increased levels of damage-associated molecular patterns (alarmins) that trigger an inflammatory response and possibly promote autoimmune and neurological disorders. OS skews type-1 immunity for defenses against pathogens and cancers more toward type-2 immune responses to self-antigens (autoimmunity). The toxicants may directly affect the innate and adaptive immune cells inducing this skewing, or they may modify portions of gut microbial species and strains and their production of metabolites that indirectly affect systemic immunity. These latter toxicant influences require metabolomic analysis of the differential structures and activities of the microbial metabolites. The damaging effects of OS and inflammation disrupting immune homeostasis and leading to disorders are reviewed and discussed. The need for well-designed studies that allow for standardized comparison of exposures and related effects are emphasized, and their real-world limitations noted. Full article

Objectives: The present study evaluated the association between plasma concentrations of selected endocrine-disrupting chemicals (EDCs)—bisphenol A (BPA), methylparaben (MeP), propylparaben (PrP), 4-nonylphenol (4-NP), 4-octylphenol (4-OP), bis(2-ethylhexyl) phthalate (DEHP), and imazalil (IMZ)—and prior coronavirus disease 2019 (COVID-19) status. Methods: Plasma EDC levels were quantified via gas chromatography–mass spectrometry in 262 voluntary blood donors (121 convalescents and 141 controls) at the Regional Centre for Transfusion Medicine in Bialystok, Poland. Results: The cohort exhibited widespread environmental exposure to all selected EDCs (BPA: 1.14 ng/mL, MeP: 1.20 ng/mL, PrP: 1.38 ng/mL, 4-NP: 1.90 ng/mL, 4-OP: 0.57 ng/mL, DEHP: 49.68 ng/mL, IMZ: 20.06 ng/mL). Convalescents had significantly higher concentrations of MeP, PrP, 4-OP, and 4-NP. Logistic regression revealed that MeP, PrP, and 4-NP were significantly associated with prior COVID-19 status, increasing infection odds by 80%, 70%, and 63%, respectively. While 4-OP was strongly associated with prior COVID-19 status (odds ratio > 300 per unit change and 1.79 per 0.1 unit change), the wide confidence interval for the unit change estimate requires cautious interpretation. Conclusions: These findings suggest a strong link between selected paraben and alkylphenol exposure and prior COVID-19 status in blood donors. Additionally, the high IMZ levels highlight the need for urgent evaluation of its safety and environmental prevalence. Full article

Butyl benzyl phthalate (BBP), a widely used endocrine-disrupting chemical, has been associated with reproductive toxicity; however, its long-term effects during aging remain poorly understood. In the present study, we examined the effects of prolonged BBP exposure on the male reproductive system using naturally aged C57BL/6J mice. Mice received BBP at 169 μg/kg/day in drinking water for 10 or 22 months and were analyzed at 24 months of age. No significant differences in body weight, food intake, or water consumption were observed among the experimental groups. Representative gross images showed apparent distension and dark-red discoloration of the seminal vesicles in BBP-exposed aged mice. Compared with Young mice, the BBP-exposed aged groups showed higher expression of IL-1β, IL-6, TNFα, SOD1, and SOD2 and lower CAT expression in the seminal vesicle. H₂DCFDA fluorescence showed a non-significant increasing trend. Because an untreated age-matched Old group was not included in the seminal vesicle analyses, the effects of aging and BBP could not be distinguished. In contrast, the testis showed limited changes in inflammatory cytokine-, antioxidant enzyme-, and steroidogenesis-related gene expression and in H₂DCFDA fluorescence relative to the untreated Old group. Exploratory miRNA sequencing of pooled testicular RNA and comparison with a TM3 Leydig cell dataset identified miR-664-5p as a candidate showing higher relative abundance in both datasets. TargetScan analysis predicted binding sites for miR-664-5p in FOXO1 and FOXO3. In BBP-treated TM3 cells, FOXO3 protein expression was decreased, and FOXO6 expression was increased, whereas FOXO1 showed no consistent dose-dependent change. These molecular findings do not establish direct regulation of FOXO proteins by miR-664-5p or explain the seminal vesicle findings. Full article

Bisphenols and phthalates are ubiquitous endocrine-disrupting chemicals with potential effects on reproductive neuroendocrine regulation, particularly during sensitive developmental windows. This review summarizes current evidence on their exposure profile, mechanisms of reproductive disruption, and female- and male-specific reproductive adversities. A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including experimental, epidemiological, biomonitoring, systematic review, and meta-analytic studies addressing bisphenols, phthalates, fertility, hormonal regulation, gametogenesis, pregnancy outcomes, and reproductive toxicity mechanisms. Bisphenols and phthalates interfere with estrogenic and androgenic signaling, hypothalamic–pituitary–gonadal axis regulation, steroidogenesis, oxidative stress, inflammation, apoptosis, mitochondrial function, and epigenetic regulation. Reported outcomes include impaired ovarian function, altered oocyte development, hormonal imbalance, reduced semen quality, defective spermatogenesis, sperm DNA damage, infertility, and adverse developmental or pregnancy-related effects. However, human evidence remains heterogeneous and limited by observational designs, exposure misclassification, residual confounding, and insufficient mixture assessment. Current evidence supports biological plausibility for bisphenol- and phthalate-related reproductive toxicity, but causal inference remains limited. Prospective studies with repeated biomonitoring, standardized reproductive endpoints, sex- and age-specific analyses, and improved mixture modeling are needed. A precautionary reduction in avoidable exposure appears reasonable, particularly during sensitive reproductive and developmental periods. Full article

Environmental chemical exposures are increasingly recognized as contributors to metabolic dysfunction, particularly when they occur as chronic, low-dose mixtures rather than as isolated high-dose toxicants. However, current approaches often focus on exposure intensity, single-compound hazard or isolated biomarker associations, and provide limited explanation for why individuals with comparable exposure profiles may develop markedly different metabolic outcomes. This semi-systematic review proposes an Exposure–Adaptive Capacity (EAC) framework to interpret the metabolic consequences of environmental chemical mixtures through the interaction between exposure burden and host adaptive capacity. A structured literature search covered PubMed/MEDLINE, Scopus and Web of Science records published through 30 June 2026; a reviewer-triggered PubMed/MEDLINE update was executed on 30 July 2026 using harmonized British and American dyslipidaemia/dyslipidemia terms, explicit eligibility domains and evidence-mapping procedures. The review integrates epidemiological, mechanistic, toxicological and translational evidence related to environmental chemicals, metabolic dysfunction, mitochondrial impairment, oxidative stress, inflammation, endocrine disruption, metabolic resilience and biomarkers. The evidence indicates that several chemical classes, including per- and polyfluoroalkyl substances, bisphenols, phthalates, pesticides, persistent organic pollutants and selected metals, converge on mitochondrial bioenergetics, redox regulation, inflammatory signalling, endocrine and nuclear receptor activity, nutrient-sensing networks and adipose tissue function. The EAC framework defines exposure burden as the cumulative biological pressure imposed by chemical mixtures and adaptive capacity as the organism’s functional ability to buffer, compensate for or recover from exposure-induced metabolic stress. To make the framework empirically testable, we specify measurable domains for exposure burden, adaptive capacity and EAC mismatch, and distinguish biomarkers of exposure, early biological effect, adaptive capacity, metabolic dysfunction and vulnerability. A quotient-based expression is retained only as a heuristic representation, while empirical testing is proposed through exposure-by-adaptive-capacity interaction models and complementary multidimensional approaches. The framework provides a structured basis for future exposomic, epidemiological and translational studies by shifting attention from exposure alone to the balance between environmental pressure and biological resilience. Full article

Background: Over the past decades, the global onset of menarche has progressively advanced, driven by complex interactions between metabolic, psychosocial, and environmental factors. Beyond its reproductive significance, menarche represents a critical developmental milestone that coincides with increased vulnerability to mental health difficulties. Contemporary determinants such as childhood obesity, early-life adversity, and exposure to endocrine-disrupting chemicals (EDCs) may accelerate pubertal timing while simultaneously shaping adverse psychological trajectories during adolescence. Objectives: This review aims to provide a translational and clinically oriented synthesis of modern determinants of earlier menarche and their associations with mental health outcomes in girls and adolescents, highlighting implications for early identification, prevention, and integrated clinical care. Methods: We conducted a narrative review mapping a scoping literature search conducted using PubMed/Medline, Scopus, and PsycINFO, focusing on literature from the last decade (2016–2026), with emphasis on systematic reviews, meta-analyses, and longitudinal cohort studies. Evidence was synthesized across biological, psychosocial, and environmental domains. Results: Accumulating evidence indicates that higher childhood adiposity, psychosocial stress, and EDC exposure are consistently associated with advanced pubertal timing. Earlier menarche correlates with an elevated risk of depressive symptoms, anxiety, self-harm, and body image-related distress, although effect sizes vary across populations. Emerging longitudinal data suggest that the peri-menarcheal period represents a critical window for symptom exacerbation. These associations appear to be mediated by biological mechanisms (e.g., hormonal shifts, hypothalamic–pituitary–adrenal (HPA) axis reactivity) and social processes including peer-comparison dynamics and premature sexualization. Conclusions: Earlier menarche acts as a biopsychosocial sentinel event rather than an isolated gynecological milestone. Integrating mental health screening and anticipatory guidance into pediatric and gynecological care is essential for early risk detection. A multidisciplinary, equity-oriented approach is required to address both individual vulnerability and broader environmental determinants. Full article