# Effect of Perinatal Exposure to Metals on Lung Function Trajectories and Mitochondrial DNA Heteroplasmy from Childhood to Adolescence

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $626,647

## Abstract

PROJECT SUMMARY
 Chronic respiratory disease is a major public health problem accounting for billions of dollars in
healthcare costs and substantial morbidity and mortality for individuals and families worldwide. Recently the
field of Developmental Origins of Health and Disease (DOHaD) has demonstrated the key role that perinatal
life plays in determining adult health by setting growth trajectories that carry forward from fetal fetal/infancy life
stages. We propose that environmental metal exposures in utero and in infancy set in motion adverse
respiratory health conditions that manifest later in life, and can first be measured during adolescence, a period
of rapid lung growth and development. Evidence regarding the impact of metal exposure, particularly mixtures
of metals, on lung growth in childhood is lacking and may explain a substantial proportion of later life
respiratory disease given their prevalence. This makes perinatal metal exposures a global health concern. The
effects of early life metal exposures vary based not only on dose, but also on the timing of exposure.
Therefore, research is urgently needed to better understand the developmental windows that explain the later
life health effects from perinatal exposures, as well as the molecular mechanisms through which they influence
children’s lung growth.
 To address these issues we will time- and cost-effectively conduct a longitudinal study of metals and
lung function by leveraging the infrastructure of the Programming Research in Obesity, Growth, Environment,
and Social Stressors (PROGRESS) study, a well-characterized prospective birth cohort based in Mexico City.
The proposed study will phenotype 600 children aged 13-16 years who have been followed since pregnancy,
thereby conducting a prospective, longitudinal study that covers pregnancy, infancy, childhood and
adolescence and linking these data with gold standard lung growth phenotyping using pre- and post-
bronchodilator spirometry at two time points during adolescence. We will use state of art exposure biomarkers
for metals assessed by laser ablation-inductively coupled plasma mass spectrometry to measure metal
exposure in a time sensitive, yet cumulative manner from pregnancy to childhood. Finally, we use biomarkers
of cumulative oxidative stress assessed by mitochondrial DNA damage in nasal cells, the upper most end of
the respiratory tract, and a natural target tissue. Our goal is to use dose and time-specific measures of toxic
metals to assess their effects on lung growth trajectories individually and as a mixture. We hypothesize that
metals adversely affect lung growth trajectories via oxidative stress that can be estimated in the respiratory
tract using nasal cell heteroplasmy, a count of mitochondrial DNA mutations correlating with cumulative
oxidative stress. We anticipate that our findings will generate novel information on the impact of in utero and
early-life metal exposure on lung function and will inform prevention a...

## Key facts

- **NIH application ID:** 10446235
- **Project number:** 1R01ES033245-01A1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Maria Jose Rosa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $626,647
- **Award type:** 1
- **Project period:** 2022-05-18 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446235

## Citation

> US National Institutes of Health, RePORTER application 10446235, Effect of Perinatal Exposure to Metals on Lung Function Trajectories and Mitochondrial DNA Heteroplasmy from Childhood to Adolescence (1R01ES033245-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10446235. Licensed CC0.

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