Neonatal Metabolomic Profiles Related to Prenatal Arsenic Exposure

Abstract

Prenatal inorganic arsenic (iAs) exposure is associated with health effects evident at birth and later in life. An understanding of the relationship between prenatal iAs exposure and alterations in the neonatal metabolome could reveal critical molecular modifications, potentially underpinning disease etiologies. In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was used to identify metabolites in neonate cord serum associated with prenatal iAs exposure in participants from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort, in Gómez Palacio, Mexico. Through multivariable linear regression, ten cord serum metabolites were identified as significantly associated with total urinary iAs and/or iAs metabolites, measured as %iAs, %monomethylated arsenicals (MMAs), and % dimethylated arsenicals (DMAs). A total of 17 metabolites were identified as significantly associated with total iAs and/or iAs metabolites in cord serum. These metabolites are indicative of changes in important biochemical pathways such as vitamin metabolism, the citric acid (TCA) cycle, and amino acid metabolism. These data highlight that maternal biotransformation of iAs and neonatal levels of iAs and its metabolites are associated with differences in neonate cord metabolomic profiles. The results demonstrate the potential utility of metabolites as biomarkers/indicators of in utero environmental exposure.

Urinary1H NMR metabolomics profile of Italian citizens exposed to background levels of arsenic: a (pre)cautionary tale

“…The overall urinary metabolomics profile described here is consistent with the one identified in a rat model treated with realgar (a medicament that contain over 90% of tetraarsenic tetrasulfide) (Wei et al 2009), where perturbation of TCA cycle together with increased TMAO, taurine, ketone bodies, and choline, and decreased hippurate and lactate levels, were correlated to As exposure. Similar modifications have also been described in a neonatal population delivered by women living in areas with elevated As levels in drinking water (BEAR cohort), and related to prenatal As exposure (Laine et al 2017).…”

“…As-induced metabolomic perturbations have been observed in animal models as a consequence of long term and acute high dose exposure (Wei et al 2009, Huang et al 2013, Garc ıa-Sevillano et al 2014a, 2014b, Wang et al 2014. Several recent studies reported on the use of metabolomics to investigate the effect of long-term exposure to low doses of As on the biological profile of environmentally or occupationally exposed individuals (Shen et al 2013, Dudka et al 2014, Zhang et al 2014, Garc ıa-Sevillano et al 2015, Laine et al 2017. Metabolomics studies are commonly performed on urine samples, due to the ease of their collection and to the possibility of a direct correlation between urinary As levels and the As-exposure metabolomics signature.…”

Metabolomics as a powerful tool to decipher the biological effects of environmental contaminants in humans

“…The search identified publications that applied metabolomics to biological fluids of human populations environmentally exposed to contaminants (Table 1). Sixteen publications (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) studied the general population, including -for 7 of them -specifically vulnerable individuals: pregnant women, children or elder persons (9,12,14,(20)(21)(22)(23). The other studies concerned occupational exposure (24)(25)(26)(27)(28)(29).…”

“…Reactive oxygen species (ROS) -mediated oxidative stress, and to a lesser extent, nitrosative stress, may be considered as one of the potential modes of action of metals and PAHs: all studies have shown changes in levels of metabolites indicating oxidation both for exposure to As, Cd, V, PAHs or to more complex mixtures (8,(10)(11)(12)15,16,19,(22)(23)(24): TCA-cycle disruption and amino-acid metabolism impairment evoke a mitochondrial dysfunction with insufficient energy production. Perturbation of lipid metabolism may also be due to oxidative or inflammatory processes (12,19,22,24). These modes of action have been related to liver and renal dysfunction, particularly for As and Cd (8,10,15,23).…”

Toxic metals in amniotic fluid and altered gene expression in cell‐free fetal RNA

“…In summary, while toxic metals are known to cross the placental barrier and have been readily measured in cord blood serum at birth, amniotic fluid provides a unique biological matrix allowing for direct measure of both toxic metals exposure and alteration of fetal gene expression within the fetal compartment. Our findings show fetal exposure to heavy metals can be measured using amniotic fluid and that the NanoString technology can be applied to the measurement of fetal gene expression in this context.…”