Manganese in teeth and neurobehavior: Sex-specific windows of susceptibility

Abstract

Background Manganese (Mn) is an essential element required for growth and development, but higher body burdens have been associated with neurobehavioral decrements in children. Objectives We examined whether prenatal or postnatal Mn measured in deciduous teeth was associated with scores on a test of visuospatial learning and memory. Methods Deciduous teeth were collected from 142 participants (ages 10–14 years) residing near varied ferro-manganese industry in Italy. Mn concentrations were measured in prenatal and postnatal tooth regions by laser ablation inductively coupled plasma mass spectrometry (ICP-MS). The Virtual Radial Arm Maze (VRAM), an animal-human analogue task, was used to assess visuospatial learning and memory. We used generalized additive, linear and zero-inflated Poisson mixed regression models to estimate associations between prenatal or postnatal Mn concentrations and repeated measures of all four VRAM outcomes: time, distance, working and reference memory errors. Effect measure modification by sex was examined in stratified models. Results U-shaped associations between prenatal Mn and VRAM outcomes were observed among girls only (pGAMM =0.001 to 0.02 in stratified models). Compared to the mid-tertile of prenatal Mn, girls in the highest tertile took 7.7 seconds [95% CI: −6.1, 21.5] longer to complete the task, traveled 2.3 maze units [0.1, 4.4] farther, and committed more working and reference memory errors (β for count ratio=1.33 [1.01, 1.83]; 1.10 [0.98, 1.24], respectively). This association was not observed among boys. In contrast, for postnatal Mn, no significant associations were found, and patterns were similar for boys and girls. Conclusions The prenatal period may be a critical window for the impact of environmental Mn on visuospatial ability and executive function, especially for females.

Biomarkers of environmental manganese exposure and associations with childhood neurodevelopment: a systematic review and meta-analysis

“…These results suggested that Mn associations were partly driven by exposure timing and modified by sex. Three studies also found that tooth Mn concentrations were higher in the prenatal than postnatal period [42,48,55], indicating a greater demand for manganese in the prenatal period. No significant associations were observed between neurodevelopmental outcomes and Mn in saliva, toe nail [8], and urine [60] (see Table 2).…”

Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity

“…In addition to the sex-specific difference in thyroid follicle size in Slc30a10 +/+ versus Slc30a10 KO/KO mice, we also observed sex-specific differences in biliary copper levels and bile flow rates ( Figure 5, E and G). Although some of this may be attributed to intra-sex variability, other studies have reported sex-specific differences in Mn levels in individuals living near ferro-Mn industries, in rats fed diets deficient or adequate in Mn, and in children with polymorphisms in Mn transporters (26,40,41). More research is required to understand the impact of sex on metal homeostasis in health and disease.…”

Neurotoxicity of manganese: Indications for future research and public health intervention from the Manganese 2016 conference

“…In a longitudinal assessment in this area, higher levels of Mn in drinking water, but not hair Mn, were associated with lower Performance IQ in girls, whereas the opposite was observed in boys (Dion et al, 2018). Evidence of sex-specific neurodevelopmental effects of Mn were presented at the conference also for motor functions (Chiu et al, 2017), visuospatial ability (Bauer et al, 2017). Teeth Mn reflecting early life exposure resulted a significant predictor for the same motor functions (Chiu et al, 2017) and visuospatial ability (Bauer et al, 2017), and Mn concentrations in dentine was influenced by common SNPs of Mn transporter genes SLC30A10 and SLC39A8, with sex differences (Wahlberg et al, 2018).…”

“…Evidence of sex-specific neurodevelopmental effects of Mn were presented at the conference also for motor functions (Chiu et al, 2017), visuospatial ability (Bauer et al, 2017). Teeth Mn reflecting early life exposure resulted a significant predictor for the same motor functions (Chiu et al, 2017) and visuospatial ability (Bauer et al, 2017), and Mn concentrations in dentine was influenced by common SNPs of Mn transporter genes SLC30A10 and SLC39A8, with sex differences (Wahlberg et al, 2018). Finally, coexposure to Mn and depression during pregnancy was shown as having an impact on developmental Bayley scores among the children at 24 months of age (Munoz-Rocha et al, 2018).…”