Sex-specific associations between co-exposure to multiple metals and visuospatial learning in early adolescence

Abstract

The predisposition, severity, and progression of many diseases differ between males and females. Sex-related differences in susceptibility to neurotoxicant exposures may provide insight into the cause of the observed discrepancy. Early adolescence, a period of substantial structural and functional brain changes, may present a critical window of vulnerability to environmental exposures. This study aimed to examine sex-specific associations between co-exposure to multiple metals and visuospatial memory in early adolescence. Manganese (Mn), lead (Pb), chromium (Cr), and copper (Cu) were measured in blood, urine, hair, nails, and saliva of 188 participants (88 girls; 10–14 years of age). Visuospatial memory skills were assessed using a computerized maze task, the virtual radial arm maze (VRAM). Using generalized weighted quantile sum regression, we investigated sex-specific associations between the combined effect of exposure to the metal mixture and visuospatial working memory and determined the contribution of each component to the outcome. The results suggest that sex moderates the association between the metal mixture and visuospatial learning for all outcomes measured. In girls, exposure was associated with slower visuospatial learning and driven by Mn and Cu. In boys, exposure was associated with faster visuospatial learning, and driven by Cr. These results suggest that (a) the effect of metal co-exposure on learning differs in magnitude, and in the direction between sexes, and (b) early adolescence may be a sensitive developmental period for metal exposure.

Associations of Diet Quality and Heavy Metals with Obesity in Adults: A Cross-Sectional Study from National Health and Nutrition Examination Survey (NHANES)

“…Our study also observed stronger associations between heavy metals and obesity among women and older participants. Women are more susceptible to heavy metals than men due to the different redox homeostasis processes, hormonal influences (sexual maturation and menopause), and immune responses between the sexes [ 46 , 47 ]. Moreover, behavioral factors, such as smoking and occupational exposure, might affect the different susceptibility between men and women.…”

Nephrotoxic Metal Mixtures and Preadolescent Kidney Function

“…(III) In the third set of analyses, we estimated the MMBs as described in the previous section, categorized them into quartiles, applied a second WQS on the MMBs, and assessed the association between this second level index and the outcome using linear regressions. (IV) In our final set of analysis, we combined all combinations of the exposure biomarkers and metals using a single, omnibus WQS index and measured the association between this index and the outcome using a linear regression [29]. All regression coefficients were exponentiated to represent percentfold-changes in the outcome for a 1-quartile increase in the corresponding exposure level.…”

“…This can lead to misleading and uninformative exposure estimates for some chemicals in a mixture when a single exposure media (e.g., blood or urine) is used as a proxy of exposure, thus leading to inaccurate estimates for the effects of the mixture as a whole [25,26]. We have previously reported on a potential method to address this issue, namely, quantifying exposure through multi-media biomarkers (MMBs), estimates of exposure derived using environmental mixture methods across different biological media [27][28][29]. MMBs have proven useful in uncovering the effects of metal mixtures on neurodevelopment [27][28][29]; however, to our knowledge they have not been applied to the role of metal mixtures on kidney function.…”

“…We have previously reported on a potential method to address this issue, namely, quantifying exposure through multi-media biomarkers (MMBs), estimates of exposure derived using environmental mixture methods across different biological media [27][28][29]. MMBs have proven useful in uncovering the effects of metal mixtures on neurodevelopment [27][28][29]; however, to our knowledge they have not been applied to the role of metal mixtures on kidney function.…”

Prenatal trace elements mixture is associated with learning deficits on a behavioral acquisition task among young children

“…Neurodevelopmental studies increasingly emphasize the need for mixtures‐based perspectives in evaluating exposure‐related effects (Claus Henn et al., 2014; Dórea, 2019; Karri et al., 2016; Merced‐Nieves et al., 2021; Sanders et al., 2015; Vuong et al., 2020). To date, several combinations of prenatal and postnatal mixtures have been associated with differences in both cognitive and behavioral development such as decreased intelligence quotient (IQ) scores (Bauer et al., 2020; Levin‐Schwartz et al., 2021; Wasserman et al., 2018), increase in internalizing behaviors like anxiety (Horton et al., 2018) and fear (Cowell et al., 2021), and slower visuospatial learning (Rechtman et al., 2020). Although these studies examined mixtures of different elements, lead (Pb), manganese (Mn), and arsenic (As) were most consistently identified as the top contributors to neuropsychological deficits of the different mixtures with cadmium (Cd) closely behind.…”