Untargeted metabolomics reveals that multiple reproductive toxicants are present at the endometrium

Silva, Emily; Walker, Douglas I.; Fuentes, Zoe Coates; Pinto‐Pacheco, Brismar; Metz, Christine N.; Gregersen, Peter K.; Mahalingaiah, Shruthi

doi:10.1016/j.scitotenv.2022.157005

Cited by 7 publications

(2 citation statements)

References 29 publications

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“…Identifying biochemical and phenotypic features that contribute to allostasis-an individual's metabolic resilience to environmental stress-has been offered to approach an actionable endophenotype of external exposures 55 (eg, with epidemiological, epigenetic, and transcriptional studies of air pollution [56][57][58] and heavy metal studies of obesity and hypertension [59][60][61][62] ). In addition, most studies have focused on molecules in biofluids that directly reflect external exposure (eg, microplastics, disinfectants, pesticides), [63][64][65][66][67][68][69][70] not necessarily capturing a broad host biological response to these exposures. Finally, model system studies have offered important insights into potential mechanisms, 71 though whether their findings apply to broader geographically diverse populations in the real world remains less unclear.…”

Section: Discussionmentioning

confidence: 99%

Proteomics, Human Environmental Exposure, and Cardiometabolic Risk

Perry,

Zhang,

Murthy

et al. 2024

Circulation Research

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Rationale: The biological mechanisms linking environmental exposures with cardiovascular disease (CVD) pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures, and examine their associations with cardiometabolic and respiratory disease (CMD) in observational cohort studies. Methods: We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in nearly 3000 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study across 4 centers using penalized and ordinary linear regression. In >3500 participants from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS), we evaluated the prospective relations of proteomic signatures of the envirome with CVD and mortality using Cox models. Results: Proteomic signatures of the envirome identified novel/established CVD-relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to CMD and respiratory phenotypes (e.g., body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of CVD/mortality (1428 events; FHS: HR=1.16, 95% CI 1.08-1.24, P=1.77e-05; JHS: HR=1.25 95% CI 1.13-1.38, P=6.38e-06; HR expressed as per 1 standard deviation increase in proteomic signature), robust to adjustment for known clinical risk factors. Conclusions: Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with CMD and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted.

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Section: Discussionmentioning

confidence: 99%

Proteomics, Human Environmental Exposure, and Cardiometabolic Risk

Perry,

Zhang,

Murthy

et al. 2024

Circulation Research

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“…Typical concentrations across the globe range from 10 to 200 ng/ml found in urine, with the low molecular weight phthalates showing the highest urine concentrations (Zhang et al, 2021). Phthalate metabolites have been also detected in other body matrices such as semen, cord blood, breast milk and endometrium (Silva et al, 2022;Zhang et al, 2021) albeit at significant lower levels.…”

Section: Introductionmentioning

confidence: 99%