Geller RJ, Wesselink AK, Claus Henn B
… +6 more, Upson K, Vinceti M, Harmon QE, Baird DD, Wegienka G, Wise LA
Environ Health Perspect
· 2025 Apr · PMID 40063901
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BACKGROUND: Uterine leiomyomata (UL), hormone-dependent neoplasms, are a major source of gynecologic morbidity. Metals are hypothesized to influence UL risk through endocrine disruption, and their effects may vary by vit...BACKGROUND: Uterine leiomyomata (UL), hormone-dependent neoplasms, are a major source of gynecologic morbidity. Metals are hypothesized to influence UL risk through endocrine disruption, and their effects may vary by vitamin D status. OBJECTIVE: We estimated associations of a metal mixture with incident UL, overall and by vitamin D status. METHODS: We analyzed data from the Study of Environment, Lifestyle and Fibroids, a Detroit-area prospective cohort study of 1,693 black women 23-35 years of age. We measured concentrations of 17 metals/metalloids in whole blood and 25-hydroxyvitamin D [25(OH)D] in serum collected at baseline (2010-2012). Participants underwent ultrasonography at baseline and after 20 months to detect UL. We used Bayesian kernel machine regression to estimate adjusted associations () of the metal mixture with probit of incident UL. We also ran Cox regression models with interaction terms to estimate incidence rate ratios (IRR) by vitamin D status. RESULTS: Among 1,132 UL-free participants at baseline, 832 (73%) had vitamin D deficiency [25(OH)D ] and 117 (10%) developed UL within 20 months. Increasing all metals from their 50th to 75th percentiles was weakly positively associated with UL overall [; 95% credible interval (CrI): , 0.16] and among vitamin D-deficient participants (; 95% CrI: 0.01, 0.24), driven by cadmium (overall and vitamin D-deficient) and mercury (vitamin D-deficient only). Increasing cadmium from its 25th to 75th percentile was positively associated with UL overall (; 95% CrI: , 0.11) and among vitamin D-deficient participants (, 95% CrI: 0.02, 0.24). In Cox models, cadmium [; 95% confidence interval (CI): 1.07, 2.24, per 1-unit increase in standardized concentration] and mercury (; 95% CI: 0.99, 1.92) were positively associated with UL among vitamin D-deficient participants. DISCUSSION: The metal mixture was positively associated with incident UL, but the association was weak and imprecise. We observed a stronger association among vitamin D-deficient participants that was driven by cadmium and mercury. https://doi.org/10.1289/EHP15218.
Lin C, Liu R, Sutton C
… +3 more, DeWan AT, Forastiere L, Chen K
Environ Health Perspect
· 2025 Apr · PMID 40062909
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BACKGROUND: Emerging evidence identifies ambient particulate matter (PM) with an aerodynamic diameter () as a modifiable risk factor for dementia, but the potential health benefits gained by enacting regulations that re...BACKGROUND: Emerging evidence identifies ambient particulate matter (PM) with an aerodynamic diameter () as a modifiable risk factor for dementia, but the potential health benefits gained by enacting regulations that reduce remain unclear. OBJECTIVES: Our aim was to estimate the total effects of hypothetical ambient interventions starting in late life on the risk of dementia in a cohort using the parametric g-formula. METHODS: We used data from 291,495 participants in the UK Biobank cohort who were free of dementia and y of age at baseline (2010). We estimated the total effects of hypothetical ambient interventions (achieving annual average standards of , , and ) from 2010 to 2019 on the risk of dementia by calculating the difference between the estimated 10-y risk of dementia under a specified hypothetical intervention and the risk under no intervention using the parametric g-formula. RESULTS: In comparison with no intervention, the estimated 10-y risk difference of dementia was per 1,000 population [95% confidence interval (CI): , ], per 1,000 population (95% CI: , ), per 1,000 population (95% CI: , ), with interventions achieving annual average standards of , , and , respectively. DISCUSSION: The estimated 10-y risk of dementia decreased if the individual ambient exposure was reduced due to more stringent standards in late life in comparison with the natural course without intervention on ambient exposure. Our findings, obtained using the parametric g-formula-a causal inference method that can directly evaluate the impact of hypothetical interventions-suggest that policies reducing ambient pollution may lower the risk of dementia among UK Biobank participants who would experience more stringent ambient standards in late life. https://doi.org/10.1289/EHP14723.
Pastor-Barriuso R, Gutiérrez-González E, Varea-Jiménez E
… +19 more, Gómez-Ariza JL, Castaño-Vinyals G, Aragonés N, Molina AJ, Dierssen-Sotos T, Fernández-Tardón G, Amiano P, Ederra-Sanz M, Moreno V, Jiménez-Moleón JJ, Molina-Barceló A, Marcos-Gragera R, Casabonne D, Alguacil J, Gómez-Gómez JH, García-Barrera T, Kogevinas M, Pollán M, Pérez-Gómez B
Environ Health Perspect
· 2025 Apr · PMID 40052947
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BACKGROUND: Toenails are promising biomarkers of long-term metal exposure in epidemiological studies, but their accuracy may be compromised by systematic and random errors associated with heterogeneous toenail sample mas...BACKGROUND: Toenails are promising biomarkers of long-term metal exposure in epidemiological studies, but their accuracy may be compromised by systematic and random errors associated with heterogeneous toenail sample masses, as well as by substantial variability across laboratory batches. OBJECTIVES: We propose a novel modeling approach to calibrate toenail metal concentrations for the heterogeneity in sample masses and the variability between batches. METHODS: We developed a heteroscedastic spline mixed model relating sample mass and laboratory batch with measured concentrations, allowing for an average bias in measurements over all batches as a smooth function of sample mass, random variation in mass-related biases across batches, and mass-related heterogeneity in within-batch error variance. The model allowed partitioning the total variance of measured concentrations into the extraneous variances (due to different sample masses and laboratory batches) and the intrinsic variance (resulting from distinct metal exposures). We derived calibrated metal concentrations from the model by removing both sources of extraneous variation and estimating the predicted concentrations had all toenail samples been analyzed in a single batch and of the same mass. We provide the R script COMET (COrrected METals) to fit the proposed model, extract variance components, and calibrate metal concentrations. RESULTS: In a multicase-control study in Spain (MCC-Spain) with toenail determinations for 16 metals in 4,473 incident cases of five common cancers and 3,450 population controls, sample mass and batch accounted for 26%-60% of the total variance of measured concentrations for most metals. In comparison with calibrated concentrations, odds ratios for measured concentrations were biased by toward or away from the null in one-quarter of the estimated metal-cancer associations. DISCUSSION: The proposed model allows correcting toenail metal concentrations for sample mass heterogeneity and between-batch variability and could be applied to other biological specimens of heterogeneous size, distinct laboratory techniques, and different study designs. https://doi.org/10.1289/EHP14784.
Yang Y, Jiao L, Huang Y
… +5 more, Shang H, Li E, Chang H, Cui H, Wan Y
Environ Health Perspect
· 2025 Apr · PMID 40048564
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BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, and increasing evidence suggests that exposure to environmental pollutants is associated with the i...BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, and increasing evidence suggests that exposure to environmental pollutants is associated with the increased incidence of MASLD. The farnesoid X receptor (FXR) plays an important role in the development of MASLD by regulating bile acids (BAs) and lipid metabolism. However, whether FXR-active pollutants are the environmental drivers of MASLD remains unclear. OBJECTIVES: This study aimed to determine whether FXR-active pollutants exist in the environment and evaluate their ability to trigger MASLD development in mice. METHODS: An FXR protein affinity pull-down assay and nontargeted mass spectrometry (MS) analysis were used to identify environmental FXR ligands in sewage sludge. A homogeneous time-resolved fluorescence coactivator recruitment assay and cell-based dual-luciferase reporter assay were used to determine the FXR activities of the identified pollutants. Targeted analysis of BAs, MS imaging, lipidomic analysis, 16S rRNA sequencing, and quantitative polymerase chain reaction were conducted to assess the ability of FXR-active pollutants to induce metabolic disorders of BAs and lipids and to contribute to MASLD development in C57BL/6N mice. RESULTS: We identified 19 compounds in the sewage sludge that had FXR-antagonistic activity, and triphenyl phosphate (TPHP) was the FXR antagonist with the highest efficacy. Mice exposed to either 10 or TPHP for 30 d had higher levels of conjugated primary BAs in enterohepatic circulation, and the BA pool showed FXR antagonistic activities. The exposed mice also had greater lipogenesis (more Oil Red O staining and high triglyceride levels) in liver. CONCLUSIONS: Nineteen FXR-antagonistic pollutants were identified in sewage sludge. FXR inhibition by the strongest antagonist TPHP may have a role in promoting MASLD development in mice by inducing a positive feedback loop between the FXR and BAs. https://doi.org/10.1289/EHP15435.
Shaffer RM, Lee AL, Nachman R
… +2 more, Christensen K, Bateson TF
Environ Health Perspect
· 2025 Apr · PMID 40048177
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BACKGROUND: Environmental epidemiologists strive to conduct research that will lead to actions that improve public health outcomes. The risk assessment process is the bridge between scientific research and policies that...BACKGROUND: Environmental epidemiologists strive to conduct research that will lead to actions that improve public health outcomes. The risk assessment process is the bridge between scientific research and policies that can impact public health. Historically, epidemiologic studies have not frequently been used to inform US Environmental Protection Agency (EPA) assessments outside of the context of air pollution. There are certain practices that the epidemiology community can adopt to facilitate the integration of epidemiologic studies into policy-relevant assessments. OBJECTIVES: The central objective of this commentary is to provide guidance to epidemiologists that will enhance the value of their studies for US EPA assessments. First, we provide an overview of the US EPA dose-response and toxicity value derivation to increase literacy about these processes across the environmental epidemiology community. Second, we provide suggestions for modeling and reporting to facilitate the use of epidemiologic studies in US EPA dose-response assessments that form the basis for decision-making. DISCUSSION: Epidemiologic research can be used in all aspects of dose-response assessment, which involves identifying a point of departure followed by specific adjustments and extrapolations to identify a toxicity value intended to prevent adverse effects across the population. To facilitate the integration of epidemiologic research into the dose-response assessment process, we provide specific recommendations for additional modeling (e.g., modeling in the low exposure range; exploring nonlinearity) and reporting (e.g., sufficient information to conduct study evaluation; more details on exposure levels in the population) in published epidemiologic research. Many of these suggestions require only additional reporting in the final manuscript or associated appendixes but would have substantial impact on the contribution of the published work to the assessment process. https://doi.org/10.1289/EHP15203.
Griebel-Thompson AK, Sands S, Chollet-Hinton L
… +5 more, Christifano D, Sullivan DK, Hull H, Camargo JT, Carlson SE
Environ Health Perspect
· 2025 Apr · PMID 40043234
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BACKGROUND: Emerging evidence has suggested negative associations between maternal urinary fluoride adjusted for specific gravity (MUFsg) and offspring intelligence quotient (IQ). Two prior studies report the MUFsg of pr...BACKGROUND: Emerging evidence has suggested negative associations between maternal urinary fluoride adjusted for specific gravity (MUFsg) and offspring intelligence quotient (IQ). Two prior studies report the MUFsg of pregnant women in the US, both in California, and more information is needed on population levels of MUFsg. OBJECTIVES: The primary objective was to measure MUFsg in a large pregnancy cohort of women recruited from health departments and academic hospitals in Ohio and Kansas. A secondary objective was to compare associations between water fluoridation level and estimated fluoride intake from tap water and MUFsg. METHODS: Pregnant women () from the ADORE (Assessment of DHA on Reducing Early Preterm Birth) cohort provided a urine sample and dietary assessment at enrollment between 14 and 20 wk gestation. MUFsg was measured by fluoride-sensitive electrode and corrected for specific gravity. Water fluoridation levels were obtained for public water systems (PWS), matched to participant residence and multiplied by their tap water intake from dietary assessment. The association between MUFsg and water fluoridation level was estimated using a generalized linear model with gamma distribution and log link. RESULTS: MUFsg (median: ; Q1, Q3: 0.6, 1.5) was correlated with PWS fluoridation (; ) and self-reported tap water consumption (; ). For 87% of the cohort, MUFsg was above the safety benchmark for pregnancy proposed in a previous study. Similarly, 76.7% lived in areas with PWS fluoridation . The median MUFsg (; Q1, Q3: 0.7, 1.5) of those living in areas with a PWS fluoridation level was higher than the median MUFsg (; Q1, Q3: 0.5, 1.2) of women living in areas with PWS fluoridation (). DISCUSSION: MUFsg in this population of midwestern US women exceeds the safety benchmark for pregnancy. While we cannot account for all sources of fluoride, MUFsg was correlated to PWS fluoridation. Because so many exceeded the safety benchmark for MUFsg, there is a need for MUFsg evaluation in other US regions, especially where the PWS fluoridation exceeds US Department of Health and Human Services recommendations (). https://doi.org/10.1289/EHP14711.
Zheng S, Zhao N, Lin X
… +7 more, Jiang L, Qiu C, Jiang J, Shu Z, Qian Y, Liang B, Qiu L
Environ Health Perspect
· 2025 Apr · PMID 40043229
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BACKGROUND: Fine particulate matter [particulate matter (PM) with aerodynamic diameter of ()] is considered a major component of ambient PM. Exposure to was shown to be associated with male reproductive system injury....BACKGROUND: Fine particulate matter [particulate matter (PM) with aerodynamic diameter of ()] is considered a major component of ambient PM. Exposure to was shown to be associated with male reproductive system injury. Ferroptosis is regarded as an iron-dependent programmed cell death that is associated with the pathological process. It has been reported that SIRT1 has protective effects on the male reproductive system. However, the underlying mechanisms of exposure to -induced testicular injury are still unexplored. OBJECTIVES: In this study, we investigated the relationship between ferroptosis and male reproductive injury after exposure to and the role of SIRT1/HIF- signaling pathway in this process. METHODS: We established a exposure model and i using Sertoli cell Sirt1 conditional knockout C57BL/6 (cKO) mice testes and primary Sertoli cells. Hematoxylin and eosin (H&E) staining were conducted to examine the histology of the mice testes. Sperm parameters and biotin tracer assay were conducted to evaluate the effects of exposure to on the mice testes. Related markers and genes related to the blood-testis barrier (BTB) and ferroptosis were measured by quantitative real-time polymerase chain reaction (qPCR), western blot, and immunofluorescence assay. siRNA transfection was used to evaluate the potential mechanism. RESULTS: Significant pathological damage and lower sperm quality were detected in mice testes exposed to . We found that exposure to damaged the BTB and inhibited the expression level of the BTB-related proteins (including Connexin 43, Occludin, Claudin 11, N-Cadherin and ZO-1). According to the enrichment analysis results, ferroptosis and HIF- signaling pathway were significantly enriched in mice testes and primary Sertoli cells exposed to . Subsequent experiments were conducted to verify the results of the enrichment analysis and revealed differences in the expression levels of HIF-, ferroptosis-related genes (including GPX4, SLC7A11, ACSL4, and HO-1) and ferroptosis-related markers [including malondialdehyde (MDA), glutathione (GSH), and ], associated with lower expression of SIRT1 after exposure to . These results suggest that exposure may be associated with ferroptosis and HIF- signaling pathway in male reproductive dysfunction. CONCLUSIONS: Taken together, and experiments verified that exposure in mice may lead to testicular dysfunction through new pathways. https://doi.org/10.1289/EHP14447.
Singh T, Gustin K, Rahman SM
… +5 more, Shiraji S, Tofail F, Vahter M, Kampouri M, Kippler M
Environ Health Perspect
· 2025 Apr · PMID 40043203
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BACKGROUND: There are indications that fluoride exposure considered to be beneficial for dental health may not be safe from a neurodevelopmental perspective. OBJECTIVE: We assessed the impact of prenatal and childhood fl...BACKGROUND: There are indications that fluoride exposure considered to be beneficial for dental health may not be safe from a neurodevelopmental perspective. OBJECTIVE: We assessed the impact of prenatal and childhood fluoride exposure on cognitive abilities at 5 and 10 years of age. METHODS: We studied 500 mother-child pairs from the MINIMat (Maternal and Infant Nutrition Interventions in Matlab) birth cohort in rural Bangladesh. Urinary fluoride concentrations were measured in the pregnant women at gestational week 8 and in their children at 5 and 10 years of age using an ion-selective electrode and adjusting for specific gravity. Cognitive abilities were assessed using the Wechsler Preschool and Primary Scale for Intelligence, Third Edition, and the Wechsler Intelligence Scale, Fourth Edition, at 5 and 10 years of age, respectively. Associations of urinary fluoride concentrations (-transformed) with cognitive abilities (raw scores) were assessed with multivariable-adjusted linear or spline regression models. Water fluoride concentrations at the time of the follow-up of the children at 10 years of age were also measured. RESULTS: Maternal urinary fluoride concentrations (median: , 5th-95th percentiles: ) were inversely associated with full-scale raw scores at 5 and 10 years [ (95% confidence interval): (, ) and (, ), respectively, by exposure doubling]. In cross-sectional analysis at 10 years, child urinary fluoride (overall median: , 5th-95th percentiles: ) above on the -scale (corresponding to ) was inversely associated with full-scale raw scores [ (95% confidence interval): (, )]. The association at 5 years of age was also negative but nonsignificant. For both prenatal and childhood exposure, associations were most noticeable with perceptual reasoning, but also verbal scores. The estimate for the association between urinary fluoride at 10 years of age and perceptual reasoning became 18% lower after adjustment for prenatal exposure. Inconsistent sex-specific differences were observed. CONCLUSION: Urinary fluoride concentrations measured prenatally and during childhood (child urinary fluoride concentrations above on the scale, corresponding to ) were associated with lower cognitive abilities, especially perceptual reasoning and verbal abilities, in Bangladeshi children. https://doi.org/10.1289/EHP14534.
Kim SY, Gassett AJ, Blanco MN
… +1 more, Sheppard L
Environ Health Perspect
· 2025 Apr · PMID 40042987
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BACKGROUND: Given the difficulty of collecting air pollution measurements for individuals, researchers use mobile monitoring to develop accurate models that predict long-term average exposure to air pollution, allowing t...BACKGROUND: Given the difficulty of collecting air pollution measurements for individuals, researchers use mobile monitoring to develop accurate models that predict long-term average exposure to air pollution, allowing the investigation of its association with human health. Although recent mobile monitoring studies focused on predictive models' abilities to select optimal designs, cost is also an important feature. OBJECTIVES: This study aimed to compare costs to predictive model performance for different mobile monitoring designs. METHODS: We used data on ultrafine particle stationary roadside mobile monitoring and associated costs collected by the Adult Changes in Thought Air Pollution (ACT-AP) study. By assuming a single-instrument, local monitoring, and constant costs of equipment and investigator oversight, we focused on the incremental cost of staff work days composed mostly of sampling drives and quality control procedures. The ACT-AP complete design included data collection from 309 sites, visits per site, during four seasons, every day of the week. We considered alternative designs by selecting subsets of fewer sites, visits, seasons, days of week, and hours of day. Then, we developed exposure prediction models from each alternative design and calculated cross-validation (CV) statistics using all observations from the complete design. Finally, we compared CV R-squared values and the numbers of staff work days from alternative designs to those from the complete design and demonstrate this exercise in a web application. RESULTS: For designs with fewer visits per site, the costs for number of work days were lower and model performance (CV ) also worsened, but with mild decline above 12 visits per site. The costs were also less for designs with fewer sites when considering at least 100 sites, although the reduction in performance was minimal. For temporally restricted designs that were constrained to have the same number of work days and thus the same cost, restrictions on the number of seasons, days of week, and/or hours of the day adversely impacted model performance. DISCUSSION: Our study provides practical guidance to future mobile monitoring campaigns that have the ultimate goal of assessing the health effect of long-term air pollution. Temporally balanced designs with 12 visits per site are a cost-effective option that provide relatively good prediction accuracy with reduced costs. https://doi.org/10.1289/EHP15100.
Gan HJ, Chen S, Yao K
… +4 more, Lin XY, Juhasz AL, Zhou D, Li HB
Environ Health Perspect
· 2025 Apr · PMID 40042913
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BACKGROUND: Plastic cutting boards are commonly used in food preparation, increasing human exposure to microplastics (MPs). However, the health implications are still not well understood. OBJECTIVES: The objective of thi...BACKGROUND: Plastic cutting boards are commonly used in food preparation, increasing human exposure to microplastics (MPs). However, the health implications are still not well understood. OBJECTIVES: The objective of this study was to assess the impacts of long-term exposure to MPs released from cutting boards on intestinal inflammation and gut microbiota. METHODS: MPs were incorporated into mouse diets by cutting the food on polypropylene (PP), polyethylene (PE), and willow wooden (WB) cutting boards, and the diets were fed to mice over periods of 4 and 12 wk. Serum levels of C-reactive protein (CRP), tumor necrosis factor- (TNF-), interleukin-10 (IL-10), lipopolysaccharide (LPS, an endotoxin), and carcinoembryonic antigen (CEA), along with ileum and colon levels of interleukin-1 (IL-), TNF-, malondialdehyde (MDA), superoxide dismutase (SOD), secretory immunoglobulin A (sIgA), and myosin light chain kinase (MLCK), were measured using mouse enzyme-linked immunosorbent assay (ELISA) kits. The mRNA expression of mucin 2 and intestinal tight junction proteins in mouse ileum and colon tissues was quantified using real-time quantitative reverse transcription polymerase chain reaction. Fecal microbiota, fecal metabolomics, and liver metabolomics were characterized. RESULTS: PP and PE cutting boards released MPs, with concentrations reaching and in diets, respectively, and displaying mean particle sizes of vs. . Mice fed diets prepared on PP cutting boards for 12 wk exhibited significantly higher serum levels of LPS, CRP, TNF-, IL-10, and CEA, as well as higher levels of IL-1, TNF-, MDA, SOD, and MLCK in the ileum and colon compared with mice fed diets prepared on WB cutting boards. These mice also showed lower relative expression of and in the ileum and colon. In contrast, mice exposed to diets prepared on PE cutting boards for 12 wk did not show evident inflammation; however, there was a significant decrease in the relative abundance of Firmicutes and an increase in Desulfobacterota compared with those fed diets prepared on WB cutting boards, and exposure to diets prepared on PE cutting boards over 12 wk also altered mouse fecal and liver metabolites compared with those fed diets prepared on WB cutting boards. DISCUSSION: The findings suggest that MPs from PP cutting boards impair intestinal barrier function and induce inflammation, whereas those from PE cutting boards affect the gut microbiota, gut metabolism, and liver metabolism in the mouse model. These findings offer crucial insights into the safe use of plastic cutting boards. https://doi.org/10.1289/EHP15472.
Environ Health Perspect
· 2025 Apr · PMID 40036665
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BACKGROUND: Environmental contamination by endocrine-disrupting chemicals (EDCs) has created serious public health, ecological, and regulatory concerns. Prenatal exposures can affect a wide range of developing organ syst...BACKGROUND: Environmental contamination by endocrine-disrupting chemicals (EDCs) has created serious public health, ecological, and regulatory concerns. Prenatal exposures can affect a wide range of developing organ systems and are associated with adverse changes to behavior, metabolism, fertility, and disease risk in the adult. The most serious and puzzling observation for some EDC exposures is the transmission of effects to subsequent unexposed generations (transgenerational effects) in animal models. This requires the induction of epigenetic aberrations to the germline that are not subject to the normal processes of erasure and resetting in subsequent generations. Understanding when and how the germline is vulnerable to environmental contaminants is an essential first step in devising strategies to prevent and reverse their effects. METHODS: Fetal mouse oocytes were collected after exposure of the dam to various concentrations of bisphenol A (BPA) or placebo. Meiotic effects were assessed by immunostaining to visualize the synaptonemal complex and recombination sites, as well as whole chromosome fluorescence hybridization probes. Enriched oocyte pools were analyzed by mass spectrometry and RNA sequencing to determine differences in histone posttranslational modifications and gene expression, respectively. RESULTS: We found germline effects across a wide range of exposure levels, the severity of which was positively associated with BPA concentration. We identified the onset of meiotic prophase as the vulnerable window of exposure and found surprising exposure-related differences in chromatin. Oocyte analysis by mass spectrometry and immunofluorescence suggested H4K20me2, a histone posttranslational modification involved in DNA damage repair, was particularly affected. Subsequent RNA-seq analysis revealed a relatively small number of differentially expressed genes, but in addition to genes involved in chromatin dynamics, several with important roles in DNA repair/recombination and centromere stability were affected. DISCUSSION: Together, our data from a mouse model suggest BPA exposure induced complex molecular differences in the germline that dysregulated chromatin and affected several critical and interrelated meiotic pathways. https://doi.org/10.1289/EHP15046.
Fang P, Konyali D, Fischer E
… +11 more, Mayer RP, Huang J, Elena AX, Orzechowski GH, Tony-Odigie A, Kneis D, Dalpke A, Krebs P, Li B, Berendonk TU, Klümper U
Environ Health Perspect
· 2025 Apr · PMID 40032488
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BACKGROUND: Antimicrobial resistance (AMR) and smoking of tobacco products are two of the most important threats to global human health. Both are associated with millions of deaths every year. Surprisingly, the immediate...BACKGROUND: Antimicrobial resistance (AMR) and smoking of tobacco products are two of the most important threats to global human health. Both are associated with millions of deaths every year. Surprisingly, the immediate interactions between these two threats remain poorly understood. OBJECTIVES: We aimed to elucidate the effect of toxic compounds from cigarette smoke, ashes, and filters on the spread of antibiotic resistance genes in human lung and environmental microbiomes. METHODS: Conjugation experiments using donor and recipient strain pairs of either or and AMR-encoding plasmids were conducted under exposure to different concentrations of cigarette smoke condensate in lung sputum medium, as well as cigarette ash and filter leachate in environmental media. We further measured reactive oxygen species (ROS) production of the donor strain under exposure to the cigarette-derived compounds to explore whether stress experienced by the bacteria could be one of the underlying mechanisms of change in plasmid transfer frequencies. Furthermore, used cigarette filters were submerged in a wastewater stream for several weeks, and the colonizing communities were analyzed using high-throughput sequencing and high-throughput quantitative polymerase chain reaction and compared with communities colonizing unused control filters. RESULTS: Exposure to cigarette smoke condensate at relevant concentrations resulted in higher transfer rates of a multidrug-resistance-encoding plasmid in artificial lung sputum medium. This was associated with higher ROS production as part of the bacterial stress response when exposed to cigarette-derived toxicants. Similar results were obtained for cigarette ash leachate in an environmental medium. Further, used cigarette filters were colonized by different microbial communities compared with unused filters. Those communities were significantly enriched with potential human pathogens and AMR. DISCUSSION: The results of this study suggest that cigarette-derived compounds can indeed promote the spread of AMR within simulated human lung and environmental conditions. This study highlights that the consumption of cigarettes has not only direct but may also have indirect adverse effects on human health by promoting AMR. https://doi.org/10.1289/EHP14704.
Yuan L, Honda Y, Madaniyazi L
… +3 more, Tobias A, Ng CFS, Hashizume M
Environ Health Perspect
· 2025 Feb · PMID 39913177
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BACKGROUND: Younger generations are projected to experience more severe climate exposure impacts during their lifetimes than older generations as global warming progresses. Despite the increasing evidence of the recent t...BACKGROUND: Younger generations are projected to experience more severe climate exposure impacts during their lifetimes than older generations as global warming progresses. Despite the increasing evidence of the recent temporal changes in heat-related mortality risks, there remains a lack of research exploring this association from a cohort perspective. OBJECTIVE: Our objective was to quantify the variation in susceptibility to short-term effects of non-optimal temperature on mortality, across generations and over the life course of specific generations, using a novel age-period-cohort approach. METHODS: An extended two-stage analytical approach was applied to a nationwide mortality dataset covering individuals born from 1866 to 2019 in all 47 prefectures in Japan. Daily mortality counts observed between 1972 and 2019 were aggregated into 5-year birth cohorts and corresponding age groups of the decedents. For each prefecture and birth cohort, the age-dependent association between ambient temperature and daily mortality was modeled using conditional quasi-Poisson regression. Then, the prefecture-specific associations were pooled across cohorts, separately for each age group, using a repeated-measure meta-regression. To model the intergenerational changes in risks, a nonlinear, continuous term for cohort was applied in the meta-analysis. RESULTS: A total of 29 million all-cause deaths were analyzed. The relative risk (RR) of heat-related mortality (99th temperature percentile compared to minimum mortality temperature) decreased across generations for elder adults (65-89 years of age), from [95% confidence interval (CI): 1.13, 1.23] for those born in 1901-1905 to (95% CI: 1.01, 1.07) for those born in 1926-1930 (). Similar to heat-related risk, the cold-related mortality risk (at first percentile) also decreased across the same cohorts (). The predicted continuous trends in heat- and cold-related mortality risks exhibited a nonlinear decline across generations. An inconsistent pattern was observed for middle-aged people (40-64 years of age) born between 1930 and 1960, with a slight increase in risks for cold and heat over generations. For cohort-specific risk trajectories, heat- and cold-related mortality risks generally increased with age, after 60 years old. DISCUSSION: This nationwide, individual-level study adopted a novel cohort perspective to investigate how population susceptibility to short-term non-optimal temperature exposure varies across generations. Our findings revealed disparities in susceptibility between generations, highlighting the importance for researchers and policymakers to consider cohort differences in efforts to promote future health advancements and reduce inequalities. https://doi.org/10.1289/EHP15226.
Hubbard S, Wolf J, Oza HH
… +3 more, Arnold BF, Freeman MC, Levy K
Environ Health Perspect
· 2025 Feb · PMID 39903556
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BACKGROUND: Studies evaluating how water, sanitation, and/or handwashing (WASH) interventions in low- and middle-income countries impact diarrheal diseases have shown inconsistent results. The prevalence of enteric patho...BACKGROUND: Studies evaluating how water, sanitation, and/or handwashing (WASH) interventions in low- and middle-income countries impact diarrheal diseases have shown inconsistent results. The prevalence of enteric pathogen infections and diarrhea are highly seasonal and climate-sensitive, which could explain heterogeneous findings. Understanding how season influences the effectiveness of WASH interventions is critical for informing intervention approaches that will be resistant under the varying weather conditions that climate change will bring. METHODS: We conducted a systematic review of the literature and meta-analysis to test whether and to what extent the impact of WASH interventions on diarrhea differs by season. We searched the literature for randomized and nonrandomized controlled WASH intervention trials and identified the season in which data were collected-rainy, dry, or both-for each study using proximate land station weather datasets. We compared the relative risk (RR) estimates for the impact of interventions on diarrhea for each study, stratified by season, and analyzed estimates using meta-analysis and meta-regression. This study is registered with PROSPERO, CRD42021231137. RESULTS: A total of 50 studies met the inclusion criteria, resulting in 34 drinking water intervention estimates, 8 sanitation intervention estimates, and 14 handwashing intervention estimates. Of the total studies, 60% () spanned more than one season, with most single-season studies (75%, ) occurring exclusively in the dry season. The effect of WASH interventions was stronger in dry seasons than in rainy seasons, with a 33% [95% confidence interval (CI): 24%, 41%] and 18% reduction (95% CI: 5%, 29%) in diarrhea risk, respectively. When stratified by type of intervention, the stronger effect size in dry seasons was consistent for water and handwashing interventions but not for sanitation interventions. CONCLUSIONS: Estimates of the seasonal impact of WASH interventions revealed larger effects in the dry season than in the rainy season overall and for water and handwashing interventions in particular. These patterns likely affected previous estimates of intervention effectiveness, which included more dry season estimates. These findings suggest the need to collect data across seasons and report seasonally stratified results to allow for more accurate estimates of the burden of disease impacted by WASH investments and to improve projections of potential impacts of these interventions under future climate conditions. These findings also underscore the need for robust WASH interventions designed to be resistant to seasonal variations in temperature and rainfall now and under future climate change scenarios. https://doi.org/10.1289/EHP14502.
Stajnko A, Pineda D, Klus JK
… +12 more, Love TM, Thurston SW, Mulhern MS, Strain JJ, McSorley EM, Myers GJ, Watson GE, Shroff E, Shamlaye CF, Yeates AJ, van Wijngaarden E, Broberg K
Environ Health Perspect
· 2025 Feb · PMID 39903555
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BACKGROUND: Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) variations are linked to age-related diseases and are associated with environmental exposure and nutritional status. Limited data, however, exi...BACKGROUND: Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) variations are linked to age-related diseases and are associated with environmental exposure and nutritional status. Limited data, however, exist on the associations with mercury exposure, particularly early in life. OBJECTIVE: We examined the association between prenatal mercury (Hg) exposure and TL and mtDNAcn in 1,145 Seychelles children, characterized by a fish-rich diet. METHODS: Total mercury (THg) was determined in maternal hair at delivery and cord blood. TL and mtDNAcn were determined relative to a single-copy hemoglobin beta gene in the saliva of 7-y-old children. Linear regression models assessed associations between THg and relative TL (rTL) and relative mtDNAcn (rmtDNAcn) while controlling for maternal and cord serum polyunsaturated fatty acid (PUFA) status and sociodemographic factors. Interactions between THg and child sex, PUFA, and telomerase genotypes were evaluated for rTL and rmtDNAcn. RESULTS: Higher THg concentrations in maternal hair and cord blood were associated with longer rTL [; 95% confidence interval (CI): 0.002, 0.016 and ; 95% CI: 0.001, 0.003, respectively], irrespective of sex, PUFA, or telomerase genotypes. Maternal serum n-6 PUFA and n-6/n-3 ratio were associated with shorter [; 95% CI: , and ; 95% CI: , , respectively] and PUFA with longer (; 95% CI: 0.032, 0.65) rTL. Cord blood n-6 PUFA was associated with longer (; 95% CI: 0.050, 0.26) rTL. Further analyses revealed linoleic acid in maternal blood and arachidonic acid in cord blood as the main drivers of the n-6 PUFA associations. No associations were observed for THg and PUFA with rmtDNAcn. DISCUSSION: Our results indicate that prenatal THg exposure and PUFA status are associated with rTL later in childhood, although not consistently aligned with our initial hypothesis. Subsequent research is needed to confirm this finding, further evaluate the potential confounding of fish intake, and investigate the underlying molecular mechanisms to verify the use of rTL as a true biomarker of THg exposure. https://doi.org/10.1289/EHP14776.