Urine Metabolic Signatures of Multiple Environmental Pollutants in Pregnant Women: An Exposome Approach

Abstract

31Exposure to environmental pollutants, particularly during pregnancy, can have adverse consequences 32 on child development but little is known about the effects of pollutant mixtures on endogenous 33 metabolism in pregnant women. We aimed to identify urinary metabolic signatures associated with 34 low level exposure to multiple environmental pollutants in pregnant women from the INMA (INfancia y 35 Medio Ambiente) birth cohort (Spain, N=750). 36 35 chemical exposures were quantified in first trimester blood samples (organochlorine pesticides, 37PCBs, PFAS), in cord blood (mercury), and twice in urine at 12 and 32 weeks of pregnancy (metals, 38 phthalates, bisphenol A). 1 H nuclear magnetic resonance (NMR) metabolic profiles were acquired in 39 the same two urine samples. We explored associations between exposures and metabolism through 40 an exposome-metabolome wide association scan and multivariate O2PLS modelling. 41Novel and reproducible associations were found across two periods of pregnancy for 3 non-persistent 42 pollutants and across two sub-cohorts for 4 of the persistent pollutants. We found novel metabolic 43 signatures associated with arsenic exposure: TMAO and dimethylamine possibly related to gut 44 microbial methylamine metabolism and homarine related to fish intake, of tobacco smoke exposure 45 related to coffee metabolism and PCBs with 3-hydroxyvaleric acid, usually released under 46 ketoacidosis. 47 These findings will have implications for further understanding of maternal-fetal health, and health 48 across the life-course. 49

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus

“…Mothers sometimes breathe dust in rooms with wallpaper or flooring containing EDCs or touch products made with BPA. A number of studies have revealed that some EDCs can be detected in the serum, amniotic fluid, breast milk, and urine of pregnant women [15,16]. Some of these may accumulate in placental tissues, and impair placental function, including plasticizers, organochlorine pesticides, personal care products, or naturally occurring EDCs found in plants.…”

Applying the exposome concept in birth cohort research: a review of statistical approaches

“…A recent study applied a O2PLS approach in pregnant women from the Spanish INMA birth cohort to assess the association between multiple chemical exposures (> 30) and urine 1 H nuclear magnetic resonance metabolomics (> 60). This allowed the identification of common route of exposures such as fish intake and oxidative stress of chemical exposures with known detrimental health effects [81]. When multiple omics profiles are available in the same individuals, cross-omics analyses investigate how exposure and/or outcome-related signals found at one molecular level correlate to those found at another level, gaining insight into the molecular cascades related to that specific exposure and/ or outcome [82].…”

The role of gene–environment interactions in lung disease: the urgent need for the exposome

“…quantification of environmental chemicals), 2) metabolic imprints of exposure or exposure-metabolite associations (e.g. total arsenic in urine associates with the gut bacteria metabolite TMAO in pregnant women [4]), 3) the biological impact of exposures (e.g. acetylcholinesterase activity is a biomarker of organophosphate exposure) and 4) processes that reflect wear and tear in the individual (e.g.…”