The developing central nervous system is particularly vulnerable to environmental toxicants. While lead poisoning has been extensively studied and public health measures to reduce exposure implemented, exposure is still high in some populations. Other toxic metals (arsenic and manganese for example) remain elevated in the environment, and the effects of arsenic and manganese on neurodevelopment remain poorly understood. Critical questions also remain regarding individual differences in susceptibility to metals (even lead) and whether combinations of neurotoxicants are synergistically toxic. Given this, the effect of joint exposure to combinations of metals is a critical public health issue, as this exposure scenario is more reflective of the real world situation. The role of iron metabolism genes, which may regulate the metabolism of multiple neurotoxic metals, may also play a key role in understanding the mechanisms by which metal mixtures produce neurotoxicity. In this project we will establish a new birth cohort in Mexico City to measure biomarkers of internal dose for manganese, arsenic and lead and analyze their interactions in predicting associations between metal exposure and neurodevelopment. Furthermore, we will study the modifying effects of iron metabolism gene variants (HFE, Transferrin, Transferrin Receptor, and Divalent Metal Transport Protein-1) on the neurotoxicity of these metals and their influence on placenta! transfer of metals. We will also explore the effect of variants in the GST-M1, T1 and P1 genes on Arsenic neurotoxicity. Our research team is particularly well situated to conduct this work as we have a long-standing collaboration with the National Institute of Public Health in Mexico, enabling us to quickly assemble highly skilled field teams for sample collection and phenotyping. Furthermore, our pilot data suggest that exposure to Mn, As and Pb are elevated in the target population, and that biomarkers of internal dose may be associated with poorer developmental outcomes. ? ? ?

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IRAP-Q (01))
Program Officer
Gray, Kimberly A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
Muñoz-Rocha, Teresa Verenice; Tamayo Y Ortiz, Marcela; Romero, Martín et al. (2018) Prenatal co-exposure to manganese and depression and 24-months neurodevelopment. Neurotoxicology 64:134-141
Wu, Shaowei; Gennings, Chris; Wright, Rosalind J et al. (2018) Prenatal Stress, Methylation in Inflammation-Related Genes, and Adiposity Measures in Early Childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study. Psychosom Med 80:34-41
Flom, Julie D; Chiu, Yueh-Hsiu Mathilda; Tamayo-Ortiz, Marcela et al. (2018) Subconstructs of the Edinburgh Postpartum Depression Scale in a postpartum sample in Mexico City. J Affect Disord 238:142-146
Jansen, E C; Zhou, L; Song, P X K et al. (2018) Prenatal lead exposure in relation to age at menarche: results from a longitudinal study in Mexico City. J Dev Orig Health Dis 9:467-472
Sun, Ryan; Wang, Zhaoxi; Claus Henn, Birgit et al. (2018) Identification of novel loci associated with infant cognitive ability. Mol Psychiatry :
Rosa-Parra, Jose A; Tamayo-Ortiz, Marcela; Lamadrid-Figueroa, Hector et al. (2018) Diurnal Cortisol Concentrations and Growth Indexes of 12- to 48-Month-Old Children From Mexico City. J Clin Endocrinol Metab 103:3386-3393
Sanders, Alison P; Saland, Jeffrey M; Wright, Robert O et al. (2018) Perinatal and childhood exposure to environmental chemicals and blood pressure in children: a review of literature 2007-2017. Pediatr Res 84:165-180
Valeri, Linda; Mazumdar, Maitreyi M; Bobb, Jennifer F et al. (2017) The Joint Effect of Prenatal Exposure to Metal Mixtures on Neurodevelopmental Outcomes at 20-40 Months of Age: Evidence from Rural Bangladesh. Environ Health Perspect 125:067015
Claus Henn, Birgit; Bellinger, David C; Hopkins, Marianne R et al. (2017) Maternal and Cord Blood Manganese Concentrations and Early Childhood Neurodevelopment among Residents near a Mining-Impacted Superfund Site. Environ Health Perspect 125:067020
Tamayo Y Ortiz, Marcela; Téllez-Rojo, Martha María; Trejo-Valdivia, Belem et al. (2017) Maternal stress modifies the effect of exposure to lead during pregnancy and 24-month old children's neurodevelopment. Environ Int 98:191-197

Showing the most recent 10 out of 78 publications