Environmental Health Perspectives[JOURNAL]
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200 papers
Prenatal Air Pollution Exposure and Autism Spectrum Disorder in the ECHO Consortium.
Ghassabian A, Dickerson AS, Wang Y … +35 more , Braun JM, Bennett DH, Croen LA, LeWinn KZ, Burris HH, Habre R, Lyall K, Frazier JA, Glass HC, Hooper SR, Joseph RM, Karr CJ, Schmidt RJ, Friedman C, Karagas MR, Stroustrup A, Straughen JK, Dunlop AL, Ganiban JM, Leve LD, Wright RJ, McEvoy CT, Hipwell AE, Giardino AP, Santos HP, Krause H, Oken E, Camargo CA, Oh J, Loftus C, O'Shea TM, O'Connor TG, Szpiro A, Volk HE, ECHO Cohort Consortium
Environ Health Perspect · 2025 Jun · PMID 40498638 · Publisher ↗
BACKGROUND: The relationship between prenatal exposure to low-level air pollution and child autism spectrum disorder (ASD) is unclear. OBJECTIVE: To examine associations of prenatal air pollution exposure with autism. ME...
BACKGROUND: The relationship between prenatal exposure to low-level air pollution and child autism spectrum disorder (ASD) is unclear. OBJECTIVE: To examine associations of prenatal air pollution exposure with autism. METHODS: We analyzed data from 8,035 mother-child pairs from 44 United States cohorts in the Environmental influences on Child Health Outcomes (ECHO) Cohort. Fine particulate matter (PM), nitrogen dioxide (NO), and 8-hour-max ozone (O) levels were estimated at residential addresses during pregnancy. Parents rated children's autism-related traits using the Social Responsiveness Scale (SRS) (mean age 9.4 years, SD=3.6) and reported physician-diagnosed ASD. We examined associations of the three air pollutants with SRS scores (10, 50, and 90 quantiles) using quantile regression and with ASD diagnosis using logistic regression. Models were run within census divisions, and coefficients were pooled in a meta-analysis. RESULTS: Average (SD) pregnancy exposures were 9.3 µg/m3 (2.7) for PM, 21.8 ppb (8.8) for NO, and 40.3 ppb (5.5) for O, with variations across census divisions. The median SRS T-score was 46 (IQR=41 to 52), and 444 children (5.5%) had an ASD diagnosis. Higher PM was associated with higher SRS scores at the 10 quantile (β=0.74, 95% CI: 0.09, 1.40) but not at the median or highest quantile. The association between PM and ASD diagnosis was highly heterogeneous, with associations present in the South Central, Mountain, and Pacific census divisions. Heterogeneity was also high in the association between NO and SRS at the median and only in the mid-Atlantic, West North Central, and South Atlantic census divisions. Higher O was associated with higher SRS scores at the median (β per IQR increment=0.83, 95% CI: 0.05, 1.61) and highest quantile (β=2.19, 95% CI: 0.06, 4.32) in the meta-analysis. Higher O also was associated with ASD. DISCUSSION: Associations with ASD outcomes were present even at low levels of air pollutants. https://doi.org/10.1289/EHP16675.
Advancing extreme heat risk assessments to better capture individually-experienced temperatures: A new approach to describe individual and subgroup vulnerabilities.
Gronlund CJ, Hondula DM, Mallen E … +8 more , O'Neill MS, Rajput M, Krayenhoff ES, Broadbent A, Grijalva SC, Larsen LS, Harlan SL, Stone B
Environ Health Perspect · 2025 Jun · PMID 40497792 · Full text
BACKGROUND: Extreme heat risk assessments often rely on epidemiologic studies that used the nearest available outdoor airport temperatures (OATs) rather than individually-experienced temperatures (IETs) and frequently la...
BACKGROUND: Extreme heat risk assessments often rely on epidemiologic studies that used the nearest available outdoor airport temperatures (OATs) rather than individually-experienced temperatures (IETs) and frequently lack key individual-level determinants of exposure, including occupation, housing, and air conditioning. This hampers efforts to characterize heat burden inequities and guide interventions for vulnerable populations. OBJECTIVES: We developed an approach to estimate individual and subgroup-specific health impacts from modeled IETs before and during extreme heat events for three U.S. cities: Atlanta, Georgia (hot-humid), Detroit, Michigan (temperate), and Phoenix, Arizona (hot-dry). METHODS: IET profiles were estimated using modeled parcel-linked population microdata, housing-specific indoor temperatures from building energy models, ambient temperatures from urban-scale climate models, and time activity patterns from surveys. We linked each IET profile to daily OATs, then fit mixed-effects regressions to predict "equivalent" OATs (eOATs), based on IET, housing, and demographics. We assigned risk ratios (RRs) from existing literature on all-cause mortality, all-cause emergency department (ED) visits, and preterm births to each person-day's eOAT and estimated 5-day-extreme-heat absolute risks (ARs) by age-race-income-occupation subgroup. RESULTS: The eOATs, RRs, and ARs differed between people due to variability in IETs and baseline health outcome incidence rates. All-cause mortality RRs ranges were 1.00-1.16 (Atlanta), 1.01-7.08 (Detroit), and 1.00-6.38 (Phoenix). All-cause-mortality ARs ranged 0.01-32 (Atlanta), 0.01-1,100 (Detroit), and 0.01-950 (Phoenix) per 100,000 persons. ED visit ARs ranges were 0.2-270 (Atlanta) and 0.04-6,200 (Phoenix) per 100,000 persons. Heat mortality ARs were higher among older adults and, only in Detroit, in young, Black, outdoor workers (median = 6.6 per 100,000) compared to young, non-Black, higher-income, indoor workers (median = 0.3 per 100,000). DISCUSSION: When IETs can be estimated or directly measured, person-specific eOATs can be used to estimate the subgroup-specific heat-health burdens that would be experienced without adaptive behaviors. This approach could be adapted for other contexts to inform climate preparedness and justice policies. https://doi.org/10.1289/EHP15223.
Pesticide Exposure Estimation across Census Tracts in Washington State: Identifying Vulnerable Areas and Populations.
Amiri S, Bryant JM, Farber DH … +2 more , Amram O, Sabel JC
Environ Health Perspect · 2025 Jun · PMID 40493741 · Publisher ↗
INTRODUCTION: Disparities in exposure to and harm associated with pesticides are established. However, high resolution spatial data on exposure to pesticides are lacking. PURPOSE: To describe the development of a pestici...
INTRODUCTION: Disparities in exposure to and harm associated with pesticides are established. However, high resolution spatial data on exposure to pesticides are lacking. PURPOSE: To describe the development of a pesticide metric for Washington State and to evaluate the associations between pesticide exposure and sociodemographic characteristics of census tracts. METHODS: We used the US cropland dataset to quantify the location and size of agricultural land. These data were overlayed with state- and county-level estimated annual agricultural pesticide use to estimate pesticide exposure at the census tract level. Sociodemographic characteristics of census tracts were from the US Centers for Disease Control and Prevention's Social Vulnerability Index (SVI). Generalized additive models evaluated the associations between pesticide exposure and each of the SVI variables. RESULTS: The median exposure to pesticides was 1.5 lbs/sq mi. Significant associations were observed between exposure to pesticides and higher percentage of population below poverty, populations unemployed, populations 65 and older, non-Hispanic white populations, those with limited English language proficiency, mobile homes, and group quarters. CONCLUSIONS: The results inform public health and policy efforts to identify areas and populations that are most vulnerable to pesticide exposure and improve the health and wellbeing of farmworkers and populations residing near agricultural areas. https://doi.org/10.1289/EHP15686.
Prenatal exposure to ambient air pollution and fetal growth trajectories in Wuhan, China.
Hu C, Liu H, Peng Y … +4 more , Hu J, Xia W, Xu S, Li Y
Environ Health Perspect · 2025 Jun · PMID 40493499 · Publisher ↗
BACKGROUND: While numerous studies have examined associations between prenatal air pollution exposure and fetal growth measures, investigations assessing longitudinal growth trajectories across multiple time points durin...
BACKGROUND: While numerous studies have examined associations between prenatal air pollution exposure and fetal growth measures, investigations assessing longitudinal growth trajectories across multiple time points during mid-to-late pregnancy remain limited. OBJECTIVES: The aim of this study is to explore the effects of prenatal exposure to air pollution during pregnancy on fetal growth trajectories. METHODS: From a prospective birth cohort in Wuhan, China recruited from 2013 to 2016, we included a total of 4283 eligible pregnant women. At 16, 24, 31, and 38 weeks of gestation, we collected ultrasound measurements, including biparietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW). Exposure to air pollution during pregnancy was estimated for the participants' residential addresses using a spatial interpolation method. Associations between air pollutants and fetal growth parameters across four exposure windows were examined using multiple informant models. A group-based trajectory modelling (GBTM) combined with multinomial logistic regression model were used to explore the effect of air pollution exposure on fetal growth trajectories. RESULTS: Four trajectory groups for AC, FL, and EFW, and three trajectory groups for BPD were selected based on GBTM. Compared with the reference trajectory group, exposure to higher PM during weeks 1-16 was significantly associated with lower odds of "fast growth group" for AC(OR=0.68, 95% CI: 0.55, 0.84) and EFW(OR=0.71, 95% CI: 0.56, 0.91). Exposures to PM, PM, NO, SO, and CO during 1-16 weeks were negatively associated with AC, FL, and EFW at 16 weeks, as well as BPD, FL, and EFW at 24 weeks. While similar negative associations were observed between air pollution exposure during 25-38 weeks and AC and EFW at 38 weeks. DISCUSSION: Our study provided evidence of negative associations between air pollution exposure during 1-16 weeks gestation and fast growth trajectory group. In addition, we observed distinct lagged associations between air pollution and fetal growth, with early-pregnancy exposure negatively related to early and mid-gestational growth, and mid-to-late pregnancy exposure negatively related to growth in the late window. These results underscore the importance of identifying critical windows of susceptibility during pregnancy and support early intervention strategies to mitigate adverse fetal developmental outcomes. https://doi.org/10.1289/EHP15204.
The Association of Arsenic Exposure and Metabolism Biomarkers with Subclinical Measures of Liver Disease: a cross-sectional investigation in the Multi-Ethnic Study of Atherosclerosis.
Wu HC, Glabonjat RA, Schilling K … +13 more , Anderson WA, Gao S, Relloso AD, LoIacono N, Slowly M, Nigra AE, Sanchez T, Sobel MH, Galvez-Fernandez M, Budoff MJ, Gamble MV, Navas-Acien A, Lazo M
Environ Health Perspect · 2025 Jun · PMID 40493026 · Publisher ↗
BACKGROUND: Long-term exposure to arsenic (As) can cause many health effects and As metabolism is key in the detoxification and elimination of As. We hypothesize that hepatic steatosis might affect As metabolism efficien...
BACKGROUND: Long-term exposure to arsenic (As) can cause many health effects and As metabolism is key in the detoxification and elimination of As. We hypothesize that hepatic steatosis might affect As metabolism efficiency. We evaluated the association of As exposure and As metabolism biomarkers with hepatic steatosis. METHODS: In this cross-sectional analysis, we analyzed data from 3,577 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), an ethnically diverse US adult population, with urinary metals and liver CT scan data available. We measured total As and As species in urine, and summarized As methylation biomarkers as inorganic (iAs%), monomethylarsonic acid (MMA%), and dimethylarsinic acid (DMA%). The ratio of liver-to-spleen (L/S) Hounsfield units (HU) < 1.0 and liver attenuation < 40 HU were used to assess the presence and severity of liver fat content. We used logistic regression to estimate the odds ratio (OR) (95%CI) of steatosis per higher interquartile range (IQR) of log-transformed total urinary As levels (ΣAs, μg/L), and per 5% higher in log-transformed As species (iAs%, MMA%, DMA%). RESULTS: The adjusted ORs (95%CI) for L/S < 1.0 were 1.09 (0.91, 1.30) per higher IQR of ΣAs, and 0.80 (0.68, 0.95), 0.69 (0.61, 0.77), and 1.24 (1.15, 1.34) per 5% higher iAs%, MMA%, and DMA%, respectively. The corresponding ORs (95% CI) for HU < 40 were 0.99 (0.75, 1.30) per higher IQR of increase ΣAs, and 0.70 (0.50, 0.91), 0.65 (0.55, 0.78), and 1.31 (1.16, 1.48) per 5% higher iAs%, MMA%, and DMA%, respectively. The associations were consistent by self-reported race/ethnicity and sex. CONCLUSIONS: Arsenic methylation capacity, but not exposure, was associated with the prevalence of hepatic steatosis. Studies are needed to examine the longitudinal association between the progression of hepatic steatosis with As metabolism biomarkers and As-related disease. https://doi.org/10.1289/EHP16728.
Associations of gestational and childhood urinary triclosan concentrations with atopic and allergic symptoms in Health Outcomes and Measures of the Environment (HOME) Study participants ages 1-12 years.
Laue HE, Fleury ES, Jackson-Browne MS … +8 more , Calafat AM, Chen A, Yolton K, Cecil KM, Newman NC, Buckley J, Lanphear BP, Braun JM
Environ Health Perspect · 2025 Jun · PMID 40489732 · Publisher ↗
BACKGROUND: Triclosan, an antimicrobial chemical that was widely used in consumer products, may increase risk of allergic diseases in children, but prospective studies are needed to clarify the association. OBJECTIVES: T...
BACKGROUND: Triclosan, an antimicrobial chemical that was widely used in consumer products, may increase risk of allergic diseases in children, but prospective studies are needed to clarify the association. OBJECTIVES: To elucidate the associations of time-varying urinary triclosan concentrations with eczema, allergic rhinitis, and wheeze. METHODS: In the HOME Study, a prospective pregnancy and birth cohort, we quantified urinary triclosan concentrations in mother-child pairs up to ten times between 16 weeks' gestation and age 12 years. Caregivers reported eczema, allergic rhinitis, and wheeze symptoms biannually until children were aged 6 years and again when they were aged 8- and 12 years. We used generalized estimating equations to estimate the covariate-adjusted association of gestational and childhood triclosan concentrations with the risk of reporting eczema, allergic rhinitis, or wheezing symptoms. RESULTS: Three hundred forty-seven mother-child dyads contributed >3,000 visits to the analysis of gestational exposures and >2,600 visits to childhood analyses. Each 2-fold higher childhood triclosan concentration was associated with a 1.23 (95% CI: 1.04, 1.46) and 1.12 (95% CI: 1.01, 1.25) times higher risk of reporting eczema and allergic rhinitis, respectively, but not wheezing (RR=0.98 [95% CI: 0.82, 1.16]). We did not observe modification by child sex. Associations of gestational triclosan with eczema, allergic rhinitis, or wheezing symptoms were null in the full sample. Child sex modified the association of gestational triclosan with allergic rhinitis and wheezing (p-interaction: 0.02; p-interaction:0.10), with 1.09 (95% CI: 1.00, 1.19) and 0.91 (95% CI: 0.83, 1.00) times the risk of allergic rhinitis symptoms among males and females respectively. CONCLUSION: Childhood urinary triclosan concentrations were associated with caregiver reported eczema, and more weakly with allergic rhinitis. Associations of gestational triclosan with allergic outcomes differed by child sex, suggesting heightened susceptibility to triclosan among males. https://doi.org/10.1289/EHP16710.
In utero per - and polyfluoroalkyl substances (PFAS) exposure and changes in infant T helper cell development among UPSIDE-ECHO cohort participants.
Meléndez DC, Laniewski N, Jusko TA … +12 more , Qiu X, Lawrence BP, Rivera-Núñez Z, Brunner J, Best M, Macomber A, Leger A, Kannan K, Miller RK, Barrett ES, O'Connor TG, Scheible K
Environ Health Perspect · 2025 Jun · PMID 40489731 · Publisher ↗
BACKGROUND: Environmental exposures to toxicants, such as per- and polyfluoroalkyl substances (PFAS), during gestation can disrupt immune development, causing long-term impacts on a child's ability to generate a well-reg...
BACKGROUND: Environmental exposures to toxicants, such as per- and polyfluoroalkyl substances (PFAS), during gestation can disrupt immune development, causing long-term impacts on a child's ability to generate a well-regulated, protective immune response. T-cells coordinate with all immune cell types to orchestrate both cellular and antibody-mediated responses. While there is compelling evidence that PFAS alters immunity in humans, the specific effects of early life PFAS exposure on infant T-cell development are unreported. Because of their central role in immunity, altered T-cell development in infants would have implications on immune responses broadly and long-term. OBJECTIVES: We seek to model longitudinal changes in the frequency of functionally distinct CD4+ T-cell subpopulations from birth through 12 months and their association with in-utero PFAS exposure. METHODS: Maternal-infant dyads were recruited as part of the UPSIDE-ECHO cohort during the first trimester between 2015 and 2019 in Rochester, New York; dyads were followed through the infant's first birthday. Maternal PFAS concentrations (PFOS, PFOA, PFNA, PFHXS and PFDA) were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6- and 12-months using mass cytometry and high-dimensional clustering methods. Linear mixed-effects models were employed to analyze the relationship between maternal PFAS concentrations and CD4+ T-cell subpopulations (n=200). All models included a PFAS and age interaction and were adjusted for parity, infant sex, and pre-pregnancy body mass index. RESULTS: In-utero PFAS exposure correlated with multiple CD4+ T-cell subpopulations in infants. The greatest effect sizes were seen in T-follicular helper (Tfh) and T-helper 2 (Th2) cells at 12 months. A log-unit increase in PFOS was associated with lower Tfh [0.17% (95%CI: -0.30, -0.40)] and greater Th2 [0.27% (95%CI: 0.18, 0.35)] cell percentages at 12 months. Similar trends were observed for PFOA, PFNA, PFHXS and PFDA. TEXT. DISCUSSION: Maternal PFAS exposures correlate with cell-specific changes in the infant T-cell compartment, including key CD4+ T-cell subpopulations that play central roles in coordinating well-regulated, protective immunity. Future studies into the role of PFAS-associated T-cell distribution and risk of adverse immune-related health outcomes in children are warranted. https://doi.org/10.1289/EHP16726.
Wildfire-season Fine Particulate Matter Exposure and Associations with Influenza and Influenza-like-illness Risk in the Western USA.
Orr A, Alden NB, Austin E … +8 more , Jaffar Z, Knudson J, Graham J, Migliaccio CT, Noonan C, Urbanski S, Wegener M, Landguth EL
Environ Health Perspect · 2025 Jun · PMID 40489657 · Publisher ↗
BACKGROUND: Influenza remains a significant public health threat, with pandemic potential. Understanding environmental factors influencing virus spread and severity is critical, particularly as wildfires become more freq...
BACKGROUND: Influenza remains a significant public health threat, with pandemic potential. Understanding environmental factors influencing virus spread and severity is critical, particularly as wildfires become more frequent and intense. While temperature and humidity's roles in virus seasonality and persistence are well understood, the impacts of air pollution-especially wildfire-specific particulate matter (PM)-on respiratory infections are less explored. OBJECTIVES: This study aimed to investigate the association between wildfire PM exposure and influenza or influenza-like illness (ILI) incidence. Specifically, we assessed (1) the long-term impact of PM exposure during the preceding wildfire season on influenza/ILI risk in the following flu season, and (2) the effects of short-term PM exposure during the active flu season. METHODS: We utilized ILI and influenza data from state health departments in six Western U.S. states (Arizona, Colorado, Montana, Nevada, Oregon, and Washington) from 2010 to 2019. We applied generalized linear distributed lag models to assess the impact of PM exposure during the preceding wildfire season on influenza or ILI risk in the subsequent flu season, as well as the effect of short-term PM exposure during the current flu season. RESULTS: Long-term exposure to wildfire PM was associated with increased influenza risk in states with influenza data: Arizona ([Rate Ratio (RR) =1.061 (1.026-1.100)]), Colorado [RR=1.067 (1.056-1.078)], Montana [RR=1.038 (1.013-1.063)], and Oregon [RR=1.049 (1.041-1.057)], per 10 µg/m PM increase. However, the states with only ILI data did not follow this pattern, revealing no observed effect in Nevada [RR=1.005 (0.920-1.097)] and a negative effect in Washington [RR=0.884 (0.842-0.919)]. Similarly, but to a lesser degree, short-term PM exposure effects were noted in states with only influenza data, but not ILI data. DISCUSSION: Our findings underscore a positive association between wildfire-specific PM and influenza risk in states with influenza data, suggesting a differential effect of PM on respiratory infections. This study supports further investigation into causative mechanisms behind these correlations, particularly considering the increasing frequency of wildfires and the resulting air quality impacts. https://doi.org/10.1289/EHP16607.
Source-specific air pollution and risk of chronic obstructive pulmonary disease: A pooled cohort study.
Cantuaria ML, Poulsen AH, Raaschou-Nielsen O … +9 more , Audureau É, Epaud R, Lanone S, Brandt J, Frohn LM, Ketzel M, Olsen A, Thygesen LC, Sørensen M
Environ Health Perspect · 2025 Jun · PMID 40489352 · Publisher ↗
BACKGROUND: The evidence linking long-term exposure to air pollution and development of chronic obstructive pulmonary disease (COPD) is still controversial. Furthermore, most studies have investigated associations with p...
BACKGROUND: The evidence linking long-term exposure to air pollution and development of chronic obstructive pulmonary disease (COPD) is still controversial. Furthermore, most studies have investigated associations with particulate matter (PM) and nitrogen dioxide (NO), disregarding their emission source and other relevant air pollutants, such as ultrafine particles (UFP) and elemental carbon (EC). OBJECTIVES: This study aimed to assess associations between long-term residential exposure to PM, NO, UFP, and EC and risk of COPD, distinguishing the effects of air pollution from local traffic and other sources. METHODS: We pooled data from two large Danish cohorts - the Diet, Cancer, and Health cohort and the Danish National Health Survey. For all participants (N = 159,769), we estimated long-term air pollution exposure to total, local traffic, and other contributions, based on complete address histories. We used Cox proportional hazards models to estimate associations between 10-year time-weighted averaged air pollution and incident COPD, adjusting for demographic, socioeconomic, and lifestyle factors, including smoking.We evaluated possible modification of these associations by sex, smoking status, and previous asthma diagnosis. RESULTS: Long-term exposures to PM, NO, UFP, and EC were associated with higher risk of COPD. The highest hazard ratio (HR) per interquartile range of total contributions was observed for PM (HR: 1.11 [95% confidence interval: 1.05, 1.17]), followed by NO (1.08 [1.04, 1.13]), UFP (1.05 [0.99, 1.11]), and EC (1.02 [1.00, 1.05]), after full adjustment. PM from other sources than local traffic was more strongly associated with COPD than PM from local traffic, while for UFP and EC, the contributions from local traffic seemed most harmful. Effect modification analyses showed stronger associations among women, never smokers, and those with an asthma diagnosis. DISCUSSION: Our findings suggest that air pollution from local traffic and other sources contribute to COPD risk, with variations depending on the pollutant type. Further research is needed to validate these findings across different populations and geographical settings. https://doi.org/10.1289/EHP16554.
Ambient temperature and injury-related emergency department visits in China and its Provinces: a large national case-crossover study.
He G, Wang Y, Liu T … +11 more , Deng X, Hu J, Er Y, Ye P, Zhu Q, Jin Y, Ji C, Lin Z, Jing F, Duan L, Ma W
Environ Health Perspect · 2025 Jun · PMID 40489136 · Publisher ↗
BACKGROUND: Temperature-related risks on non-accidental morbidity or mortality have been well documented. However, limited studies have investigated the injury morbidity risk and burden attributed to ambient temperature....
BACKGROUND: Temperature-related risks on non-accidental morbidity or mortality have been well documented. However, limited studies have investigated the injury morbidity risk and burden attributed to ambient temperature. OBJECTIVE: The current study aimed to assess the injury morbidity risk and burden attributed to ambient temperature in China. METHODS: A time-stratified case-crossover study was conducted in 31 provincial-level administrations across mainland China, and 11.5 million injury-related emergency department visits recorded in National Injury Surveillance System (NISS) during 2006-2021 were included in the study. An injury case refers to a patient who takes the first visit to the outpatient or emergency department in NISS due to an injury. Daily meteorological data were collected from the fifth generation of European ReAnalysis-Land. A two-stage approach, including a conditional logistic regression and a multilevel meta-analysis, was applied to estimate the temperature-injury association, which were then applied to assess the morbidity burden attributable to temperature. RESULTS: We observed that injury risk increased 1.2% (95%CI: 1.0%-1.4%) for a 1 °C increase in daily mean temperature with higher risk for males, children aged 0-4, and residents in tropical and subtropical zone. We also found that animal injury, violence and attack, and injury in agricultural area were more susceptible to temperature. Compared to the 2020s, we projected 5.7 times increase of injury cases and 10.4 times of attributable fraction due to temperature change driven by global warming in the 2090s under SSP5-8.5 scenario in China. Our findings might be informative for injury prevention in the context of climate change in China. CONCLUSION: Our findings identify susceptible populations, regions and mechanism-specific injuries when exposure to ambient temperature, which could be informative for injury prevention in the context of climate change in China. https://doi.org/10.1289/EHP16878.
Pre-disease biomarkers of persistent organic pollutants (POPs) and amyotrophic lateral sclerosis (ALS) risk in Finland.
Tang IW, Knekt P, Rantakokko P … +5 more , Heliövaara M, Rissanen H, Ruokojärvi P, Mukherjee R, Weisskopf MG
Environ Health Perspect · 2025 Jun · PMID 40488711 · Publisher ↗
BACKGROUND: Persistent organic pollutants (POPs) are toxic chemicals that bioaccumulate and were used in pesticides and industrial products/processes. POP-exposed occupations and environmental exposure to POPs have been...
BACKGROUND: Persistent organic pollutants (POPs) are toxic chemicals that bioaccumulate and were used in pesticides and industrial products/processes. POP-exposed occupations and environmental exposure to POPs have been associated with amyotrophic lateral sclerosis (ALS), but no study has evaluated the association with ALS when measuring POPs in samples collected before ALS onset. OBJECTIVES: This study examined the relationship between pre-disease POP exposure and ALS risk. METHODS: We conducted a nested case-control study pooling three Finnish cohorts (n=56,862). During a median follow-up of 27 years, 97 incident ALS cases were identified (mean age at ALS=68). Within each cohort, two controls per case were selected by individual matching for age, sex, municipality, and serum freeze-thaw cycles. Thirteen polychlorinated biphenyls (PCB) and nine organochlorine pesticides (OCP) were determined in serum samples collected at baseline and stored at -20C. We considered these POPs both in groups (similar congener, isomer, metabolite groups) and separately. Odds ratios and 95% confidence intervals were estimated using a conditional logistic model in a two-stage approach, further adjusting for smoking, occupation, marital status, BMI, and serum cholesterol level in primary models. RESULTS: In the main model hexachlorobenzene (HCB) showed a positive association with ALS occurrence. In contrast, Σnon-dioxin-like (NDL) PCB and ΣDDT were significantly inversely associated with ALS incidence. Most other POP groups were non-significantly inversely associated with ALS risk. In co-pollutant models, the only notable changes were that Σdioxin-like PCB and ΣHCH showed large non-significant, elevated, ORs, suggesting some negative co-pollutant confounding. There were some suggestions of stronger findings when limiting to some subgroups. DISCUSSION: We found little evidence that POPs were associated with ALS, but we identified a suggestive positive association with HCB and HCH. ΣNDL PCB and ΣDDT were inversely associated with ALS. This could suggest protective mechanisms or uncontrolled confounding by neuroprotective factors (e.g. fish oils). https://doi.org/10.1289/EHP16539.
Dietary exposure to per- and polyfluoroalkyl substances and health risk assessment in 7-year-old children in Shandong, China.
Zhang Y, Yao Q, Shi R … +7 more , Li J, Vinturache A, Wang G, Lei X, Wang Y, Tian Y, Gao Y
Environ Health Perspect · 2025 Jun · PMID 40488591 · Publisher ↗
BACKGROUND: Dietary intake, especially foods of animal-origin, is an important source of per- and polyfluoroalkyl substances (PFAS) exposure to the general population. However, the distribution of legacy and emerging PFA...
BACKGROUND: Dietary intake, especially foods of animal-origin, is an important source of per- and polyfluoroalkyl substances (PFAS) exposure to the general population. However, the distribution of legacy and emerging PFAS in different food categories is unclear, as well as their potential health risk for children. OBJECTIVES: To investigate dietary sources of PFAS and evaluate the risk for 7-year-old children in Laizhou Wan, a region with high PFAS exposure in Shandong, China. METHODS: We sampled participants from the Laizhou Wan Birth Cohort study. We administered a dietary questionnaire to the parents of 7-year-old children and measured PFAS compounds in the serum of the children (n = 154) and meat and seafood samples (n = 45). We calculated the Mann-Whitney U test to compare serum PFAS levels between children who frequently consumed a specific type of marine fish or shrimp/shellfish and those who did not. Children's dietary PFAS intake was calculated through multiplying food consumption and PFAS concentrations, and health risks were assessed by comparing the intake of PFAS with health-based guideline values. RESULTS: In seafood, perfluorooctanic acid (PFOA) (0.52 ng/g wet weight (ww)), perfluoro-6-methylheptanesulfonic acid (iso-PFOS) (0.02 ng/g ww), and 6:2 chlorinated polyfluoroethersulfonic acid (0.06 ng/g ww) had the highest median concentrations among 10 linear PFAS, 8 branched isomers of PFOA and perfluorooctanesulfonic acid (PFOS), and 3 alternatives, respectively. Particularly, PFOA levels (median, 87.80 ng/g) in (one type of marine fish), were approximately 10-100 times of those in other seafood species. Children who frequently consumed had higher serum PFAS levels, especially PFOA, than those who did not. Seafood intake accounted for more than 80% of the total estimated daily intake of PFAS. The dietary estimated weekly intake values of four PFAS (PFOA, PFOS, perfluorononanoic acid, and perfluorohexanesulfonic acid) for children (7.4 ng/kg of body weight (bw)/week) exceeded the tolerable weekly intake (4.4 ng/kg bw/week) as recommended by the European Food Safety Authority. CONCLUSION: Seafood was widely contaminated by both legacy PFAS and their alternatives in Laizhou Wan area. Intake of seafood, especially , may contribute greatly to PFAS exposure in 7-year-old children. Avoiding intake of high PFAS polluted seafood may be an important strategy to protect local children. https://doi.org/10.1289/EHP15157.
Unlocking the Power of Data Harmonization in Environmental Health Sciences: A Comprehensive Exploration of Significance, Use Cases, and Recommendations for Standardization Efforts.
Stingone JA, Bledsoe HC, Cooney G … +12 more , Diaz-Insua M, Faustman E, Fecho K, Gouripeddi R, Holmes P, Kaeli D, Lozoya O, Masci AM, Narayan H, Schmitt C, Shatz M, Tracy W
Environ Health Perspect · 2025 Jun · PMID 40479529 · Publisher ↗
BACKGROUND: The field of environmental health sciences increasingly demands comprehensive and diverse datasets, particularly in response to emerging research areas such as climate change, mixtures, and exposomics. The da...
BACKGROUND: The field of environmental health sciences increasingly demands comprehensive and diverse datasets, particularly in response to emerging research areas such as climate change, mixtures, and exposomics. The data needed to address the complexity of environmental health research questions often extend beyond the boundaries of a single study or data resource. Traditional data management approaches struggle to harmonize the ever-expanding and heterogeneous data sources needed for research in the environmental health sciences. Harmonization may help address this issue as it involves aligning and standardizing various elements of data to allow comprehensive analysis, data pooling and interpretation across studies. OBJECTIVES: The primary objective is to inform researchers about the transformative potential of embracing harmonization methodologies and to motivate contributions to ongoing efforts, thereby fostering advancements. METHODS: Using the Environmental Health Language Collaborative's Data Harmonization Use Case, we provide a practical illustration of existing data harmonization approaches, identify gaps, and emphasize future research and application directions. We selected two publicly available environmental epidemiology studies on the topic of childhood asthma and three studies on the topic of biomarkers of metals exposure during pregnancy and birth outcomes and applied several existing harmonization approaches to assess interoperability. DISCUSSION: Our process revealed the potential limitations of many existing harmonization approaches, with notable failures to identify common variables across independent datasets and lack of agreement between human and computer-based approaches. This use case identified various challenges with existing approaches, including reliance on often incomplete data documentation and large amounts of manual effort. To address these challenges, we recommend the continued advancement and dissemination of community data standards, the development of software and tools to facilitate harmonization through automation, and strategic efforts to promote engagement in data harmonization within the environmental health sciences community. Collaborative science is needed to advance our understanding of environmental contributors to health, and realizing the harmonization potential of our scientific data is a step toward improved collaboration. https://doi.org/10.1289/EHP15410.
Expanded Tox21 biological assay panel for the prediction of drug-induced liver injury and cardiotoxicity.
Xu T, Ooka M, Zhao J … +15 more , Sakamuru S, Ngan DK, Zhang L, Yang S, Travers J, Xia M, Zhao T, Klumpp-Thomas C, Zhu H, Hall MD, Ferguson S, Shaw ND, Reif DM, Simeonov A, Huang R
Environ Health Perspect · 2025 Jun · PMID 40478799 · Full text
BACKGROUND: Toxicology in the 21 Century (Tox21) assay data provide a valuable resource for the prediction of toxicity using machine learning models. However, the performances of these models previously developed using...
BACKGROUND: Toxicology in the 21 Century (Tox21) assay data provide a valuable resource for the prediction of toxicity using machine learning models. However, the performances of these models previously developed using the pre-existing Tox21 assay data were less than ideal, likely due to insufficient coverage of the biological response space by the assay targets. OBJECTIVES: This study aimed to assess whether expanding the Tox21 portfolio with new assays that probe under-represented targets/pathways related to unanticipated adverse drug effects could improve the predictive capacity of assay data for toxicity such as drug induced liver injury (DILI) and cardiotoxicity (DICT). METHODS: Models were constructed using data from the pre-existing panel of 36 assay targets and the expanded panel of 49 assay targets. A feature selection approach was used to determine the optimal number of assays needed for each model. The models were then applied to predict the potential hepatotoxicity and cardiotoxicity of compounds in the Tox21 10K compound library. RESULTS: For both DILI and DICT prediction, the best-performing models developed using the expanded assay panel required a smaller number of assays to achieve the same level of performance compared to those based on the pre-existing assays. Models constructed by combining both assay data (pre-existing + expanded) and chemical structure consistently outperformed those constructed based on assay data alone, but showed similar performance to those constructed based on chemical structure. The compounds predicted to have the highest toxic potential were experimentally verified to demonstrate the effectiveness of our models in identifying new potentially toxic compounds. DISCUSSION: The expansion of the Tox21 assay panel has significantly enhanced the predictive capacity of assay data for predicting DILI and DICT potential. This improvement underscores the importance of a diverse and comprehensive assay portfolio in advancing safety assessment. https://doi.org/10.1289/EHP16190.
Trends in serum levels of emerging and legacy per- and polyfluoroalkyl substances from 2008 to 2018: a longitudinal study in China.
Cheng X, Wang Y, Zhang J … +5 more , Guo H, Liu L, Liu L, Gao J, He M
Environ Health Perspect · 2025 Jun · PMID 40478746 · Publisher ↗
BACKGROUND: China is an important producer and consumer of per- and polyfluoroalkyl substances (PFAS), but there is limited understanding of longitudinal trends of PFAS in Chinese people. OBJECTIVES: This study investiga...
BACKGROUND: China is an important producer and consumer of per- and polyfluoroalkyl substances (PFAS), but there is limited understanding of longitudinal trends of PFAS in Chinese people. OBJECTIVES: This study investigated decadal trends in PFAS and potential sources of exposure in the Dongfeng-Tongji cohort of Chinese people and explored potential misclassification bias. METHODS: We repeatedly measured serum PFAS (containing 11 perfluorocarboxylic acids (PFCAs), 9 perfluorosulfonic acids (PFSAs), 6 PFAS precursors, and 4 PFAS alternatives) in 648 samples (collected in 2008, 2013, and 2018) from 216 Chinese residents in Hubei Province. We used linear mixed effect model to examine trends in PFAS concentrations over survey time. We also assessed the potential exposure sources of PFAS using principal component analysis-multiple linear regression (PCA-MLR) model. RESULTS: Eleven PFAS were detected in at least 80% of the population, PFOS, PFOA, and 6:2CL-PFESA being the predominant PFAS. We found a slight decrease in linear-PFOS during the 10-year period; at the same time, the levels of PFOA doubled and the detection rate of short-chain PFCAs (PFBA, PFHpA) rose. 6:2CL-PFESA (China specific PFAS alternative) remained high for a decade. Similar correlation trends between PFAS were observed at three timepoints. Comparison of our findings with those from other studies suggests the study population was exposed to three potential sources of contamination, which may represent ingestion of contaminated diets, long-range transport of atmospheric PFAS, and exposures acquired from dust, drinking water, and daily commodities. We found that serum PFAS measurement at on timepoint was similar to levels over a 5-year period but not a 10-year period. DISCUSSION: Our study provides information on serum PFAS levels in Chinese retired workers in the Dongfeng-Tongji cohort, and highlights that the risk of exposure to novel PFCAs and PFAS alternatives deserves continued attention. For longitudinal studies with long-term follow-up (e.g. more than 5 years), relying only on a single baseline serum PFAS level may generate misclassification bias resulting in expected bias towards the null and affect the estimation of health effects. https://doi.org/10.1289/EHP15340.
Prenatal Smoking Exposures and Epigenome-wide Methylation in Newborn Blood.
Hoang TT, Cosin-Tomas M, Lee Y … +53 more , Monasso G, Xu Z, Li SS, Zeng X, Starling AP, Reimann B, Röder S, Zillich L, Jima DD, Thio CHL, Pesce G, Kersten ETG, Breeze CE, Burkholder AB, Lee M, Ward JM, Consortium B, Alfano R, Deuschle M, Duijts L, Ghassabian A, Herrera LG, Jaddoe VW, Motsinger-Reif AA, Lie RT, Nawrot TS, Page CM, Send TS, Sharp G, Stein DJ, Streit F, Sunyer J, Wilcox AJ, Zar HJ, Koppelman GH, Annesi-Maesano I, Corpeleijn E, Snieder H, Hoyo C, Hüls A, Sirignano L, Witt SH, Herberth G, Plusquin M, Dabelea D, Yeung E, Wiemels JL, Richmond RC, Taylor JA, Felix JF, Håberg SE, Bustamante M, London SJ
Environ Health Perspect · 2025 Jun · PMID 40478623 · Publisher ↗
BACKGROUND: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear. OBJECTIVE: To id...
BACKGROUND: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear. OBJECTIVE: To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e., maternal exposure to secondhand smoke [SHS] exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, paternal quitting before pregnancy). METHODS: We conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements, available in a few studies, provided objective data on maternal SHS and smoking during pregnancy. Primary analyses used Illumina450K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array. RESULTS: Maternal sustained smoking associated with differential DNA methylation (false discovery rate [FDR] <0.05) at 8,862 CpGs on the 450K (n=8,148) and did not differ by infant sex. We identified over 300 novel genes not previously identified in EWAS of smoking. No differential methylation was associated with maternal SHS, maternal former smoking, or paternal smoking around conception. However, cg24805739 () was associated with paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (n=3,415), differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs). Smoking-associated CpGs in blood were strongly enriched for functional elements across multiple tissues. CONCLUSIONS: Maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. We observed minimal impacts for less studied exposures including SHS, maternal former smoking and paternal smoking. https://doi.org/10.1289/EHP16303.
A new mouse model for ozone health effects research.
Smith GJ, Immormino RM, Ferris MT … +4 more , Lester SA, Moran TP, Harkema JR, Kelada SNP
Environ Health Perspect · 2025 Jun · PMID 40471753 · Publisher ↗
BACKGROUND: Exposure to the ambient air pollutant ozone (O) is associated with adverse respiratory health outcomes. Rodent models have been used to identify mechanisms of response to O but their utility has been question...
BACKGROUND: Exposure to the ambient air pollutant ozone (O) is associated with adverse respiratory health outcomes. Rodent models have been used to identify mechanisms of response to O but their utility has been questioned owing to species differences in physiologic response, most notably exposure-induced hypothermia, which renders rodents relatively resistant to O compared to humans. OBJECTIVES: First, to test whether a recombinant inbred mouse strain from the Collaborative Cross population, CC002/Unc, provides a sensitive model of ozone response by benchmarking it to the most commonly used inbred strain, C57BL/6J. Second, to identify the genetic basis of CC002/Unc's sensitivity. METHODS: We examined the responses of CC002/Unc and C57BL/6J mice to either acute (0.4 or 0.8 ppm O x 4 hours) or repeated (0.8 ppm O x 4 hours/day x 3 or 9 weekdays) O exposure. Then, we mapped quantitative trait loci (QTL) for responses to 9 days of O in a CC002/Unc x CC005/TauUnc (O-resistant) backcross population. RESULTS: CC002/Unc was far more responsive to acute O than C57BL/6J, exhibiting significant inflammation following a single 0.4 ppm O exposure and greater inflammation and injury after 0.8 ppm O. Enhanced sensitivity of CC002/Unc mice was associated with decreased breathing frequency and diminished hypothermic responses. Following repeated exposure, C57BL/6J lungs appeared normal, while CC002/Unc lungs had eosinophilic inflammation and centriacinar fibrosis. We identified five QTLs for airway eosinophilia, including a large-effect QTL on chromosome 11 that accounted for 18% of phenotypic variation and contains genes with plausible links to aberrant immune responses. DISCUSSION: The CC002/Unc strain provides an improved model to study the effects of acute and repeated O exposure due to its enhanced sensitivity vs. C57BL/6J and more human-like thermoregulatory response. Further genetic analysis to pinpoint causal genes underlying CC002/Unc's susceptibility will provide new insights into mechanisms of O-induced lung disease. https://doi.org/10.1289/EHP15745.
Exposures to drinking water contaminants in community water systems and risk of ovarian cancer in the California Teachers Study cohort.
Spaur M, Hurwitz LM, Medgyesi DN … +12 more , Keil AP, Freeman LEB, Fisher JA, Madrigal JM, Ammons S, Spielfogel ES, Bangia K, Albert PS, Sanchez TR, Lacey JV, Jones RR, Ward MH
Environ Health Perspect · 2025 Jun · PMID 40471647 · Publisher ↗
BACKGROUND: Several drinking water contaminants are known or suspected carcinogens; however, there are only a few investigations of drinking water exposures and ovarian cancer. We evaluated associations between regulated...
BACKGROUND: Several drinking water contaminants are known or suspected carcinogens; however, there are only a few investigations of drinking water exposures and ovarian cancer. We evaluated associations between regulated contaminants in community water systems (CWS) and ovarian cancer risk in the California Teachers Study, a prospective cohort of female California educators. METHODS: Participants were cancer-free, without bilateral oophorectomy, living in California at baseline (1995-1996) with geocoded addresses linked to a CWS (N=91,127, 92%), with follow-up through 2020 (mean=19.0 years). Among participants with a residential duration at enrollment of at least 10 years, we computed 15-year (1990-2005) averages of log2-transformed arsenic, nitrate, total trihalomethanes (TTHM) (N=59,881), and uranium concentrations (N=56,314). We estimated hazard ratios (HRs, 95% CIs) for all epithelial ovarian cancers (n=424) and the high-grade serous histotype (n=203), using Cox proportional hazards regression, adjusting for age, body mass index, menopause status, oral contraceptive use, and parity. We evaluated the mixture effect (per IQR in log2 concentrations), using quantile-based g-computation. RESULTS: Almost all women (>99%) had average exposures below regulatory limits for all contaminants. In single contaminant analyses, a doubling in average uranium concentrations was associated with all ovarian cancer (HR=1.09, CI 1.02-1.16), whereas a doubling in nitrate was associated with the high-grade serous histotype (HR=1.09, CI 1.02-1.17). Findings were similar in models adjusted for other contaminants. We observed positive but imprecise associations for arsenic and TTHM in single-contaminant and contaminant-adjusted analyses. HRs per increase in the mixture were 1.39 (1.00, 1.94) and 1.75 (1.09, 2.83), for all ovarian cancer and the high-grade serous histotype, respectively. Uranium was the largest contributor (55%) to the mixture effect for all ovarian cancer, and nitrate was the largest contributor (46%) for the high-grade serous histotype. CONCLUSIONS: Novel associations between drinking water contaminants and ovarian cancer risk at levels below regulatory limits warrant further investigation. https://doi.org/10.1289/EHP16582.
The Association of Blood Lead with Cardiovascular Disease Incidence and Mortality: Findings from the Strong Heart Study Cohort.
Lieberman-Cribbin W, Nigra AE, Kupsco A … +11 more , Domingo-Relloso A, Schilling K, Zhang Y, Fretts AM, Cole S, Umans JG, Jarrett JM, Lewin M, Ruiz P, Li Z, Navas-Acien A
Environ Health Perspect · 2025 Jun · PMID 40471206 · Publisher ↗
BACKGROUND: Evidence on lead and the burden of cardiovascular disease (CVD) derived from National Health and Nutrition Examination Survey (NHANES) data, a general sample of the U.S. population, lacks sufficient represent...
BACKGROUND: Evidence on lead and the burden of cardiovascular disease (CVD) derived from National Health and Nutrition Examination Survey (NHANES) data, a general sample of the U.S. population, lacks sufficient representation of American Indians. Moreover, there is limited prospective evidence on lead and incident CVD outcomes. OBJECTIVES: We evaluated if blood lead levels were associated with CVD mortality and incidence in American Indian adults from the Strong Heart Study (SHS). METHODS: Whole blood samples collected in 1998-1999 among 1,818 participants was analyzed for lead using inductively coupled plasma mass spectrometry. CVD incidence and mortality were available through 2019. We used progressively adjusted multivariable Cox proportional hazards models to estimate the risk of composite CVD and coronary heart disease (CHD) mortality and incidence by baseline blood lead levels. RESULTS: The median (p20, p80) blood lead was 22.5 (14.2, 37.3) µg/L, similar to that of a representative sample of US adults in NHANES 1999-2000. During follow-up, 578 (31.8%) participants had a composite CVD event and 454 (25.0%) participants had a CHD event. After adjustment for demographic, lifestyle, and cardiovascular risk factors, the hazard ratio (95% CI) per change across the 80 to 20 quantiles in blood lead was 1.15 (1.02-1.30) and 1.22 (1.08- 1.37) for CVD and CHD mortality, respectively, and 1.13 (1.02-1.24) and 1.12 (0.99-1.25) for CVD and CHD incidence, respectively. In flexible dose-response models, the associations appeared to be non-linear, with a clear increased risk of CVD and CHD mortality at blood lead concentrations above 35 µg/L. DISCUSSION: Blood lead levels in American Indian adults, which are comparable to populations in the U.S. and globally, were associated with increased risk of CVD and CHD incidence and mortality. These findings highlight the importance of further reducing lead exposure, including American Indian communities. https://doi.org/10.1289/EHP16309.
Environmentally-relevant doses of bisphenol A and S exposure in utero disrupt germ cell programming across generations resolved by single nucleus multi-omics.
Zhao L, Shi M, Winuthayanon S … +3 more , MacLean Ii JA, Law NC, Hayashi K
Environ Health Perspect · 2025 Jun · PMID 40460421 · Publisher ↗
BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs), such as bisphenol (BP) A, disrupts reproduction across generations. Germ cell epigenetic alterations are proposed to mediate these transgenerational defects....
BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs), such as bisphenol (BP) A, disrupts reproduction across generations. Germ cell epigenetic alterations are proposed to mediate these transgenerational defects. Previously, we have shown that prenatal exposure to environmentally relevant doses of BPA or its substitute, BPS, caused transgenerationally maintained reproductive impairments associated with neonatal spermatogonial epigenetic changes in male mice. However, the mechanisms sustaining these changes across generations remain unclear. OBJECTIVES: This study aimed to systematically elucidate the mechanism of transgenerational inherence by prenatal BPA and BPS exposure in the murine germline from F1 to F3 generations at both transcriptomic and epigenetic levels. METHODS: Pregnant CD-1 females (F0) were orally administered BPA or BPS at doses of 0 (vehicle control), 0.5, 50, or 1000 µg/kg/b.w./day from gestational day 7 to birth. Sperm counts and motility were examined in F1, F2, and F3 adult males. THY1 germ cells on postnatal day 6 from F1, F2, and F3 males at a dose of 50 µg/kg/b.w./day were used for analysis by single-nucleus (sn) multi-omics (paired snRNA-seq and snATAC-seq on the same nucleus). RESULTS: Prenatal exposure to BPA and BPS with 0.5, 50, and 1000 µg/kg/b.w./day reduced sperm counts in mice across F1 to F3 generations. In the F1 generation, BPA or BPS exposure with 50 µg/kg/b.w./day disrupted the balance between maintaining the undifferentiated and differentiating spermatogonial populations. Differentially accessible peaks (DAPs) by snATAC-seq were primarily located in the promoter regions, with elevated activity of key transcription factors, including SP1, SP4, and DMRT1. Notably, similar gene expression and chromatin changes were observed in directly exposed F1 and F2 generations but differed in the indirectly exposed F3 generation. Approximately 80% of DAPs in F1 and F2 spermatogonia overlapped with histone post-translational modifications linked to transcription activation (e.g., H3K4me1/2/3 and H3K27ac). Across F1 to F3 generations, although BPA exerted more potent effects on gene expression in F1 spermatogonia, BPS induced longer-lasting effects. Interestingly, DMRT1 motif activity was persistently elevated in all three generations following ancestral BPA or BPS exposure. DISCUSSION: Our work provides the first systematic analyses of transgenerational gene and chromatin dynamics following prenatal exposure to BPA or BPS. These results suggest that prenatal exposure to environmentally relevant doses of BPA or BPS alters chromatin accessibility and transcription factor motif activities, consequently contributing to disrupted transcriptional levels in neonatal spermatogonia, and some are sustained to F3 generations, ultimately leading to the reduction of sperm counts in adults. https://doi.org/10.1289/EHP16981.
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