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NIH grant 1R01ES038115-01A1: Effect of gestational arsenic exposure on maternal cardiovascular health
Institute: {'code': 'ES', 'abbreviation': 'NIEHS', 'name': 'National Institute of Environmental Health Sciences', 'admin_org_id': '12500022', 'admin_funding_url': ''}. PI: Mark Jeffrey Kohr. Award: $787370.
Start: 2026-08-28T00:00:00.
PROJECT SUMMARY
The US has one of the highest maternal mortality rates among high income countries, largely resulting from
adverse cardiovascular complications in pregnancy, which account for 1 in 3 maternal deaths. Maternal heart
growth occurs in pregnancy due to hormonal changes and plasma volume expansion, and while these changes
are generally well-tolerated in healthy women, many experience adverse cardiovascular events during and after
pregnancy, the majority of which result from unknown etiology. Exposure to naturally-occurring cardiotoxic
metals like arsenic is becoming more prevalent in the US, and epidemiological findings establish arsenic as a
major driver of cardiovascular disease in the general population and a concerning contributor to adverse
cardiovascular events during pregnancy. Indeed, recent work from our group in mice shows that gestational
arsenic exposure disrupts estrogen receptor expression and impairs maternal heart growth during pregnancy,
recapitulating features of the adverse cardiovascular events observed in human pregnancies. However, key
knowledge gaps exist regarding mechanistic links between gestational arsenic exposure and cardiac pathology
in our pioneering mouse model, and potential translational implications for women exposed to arsenic during
pregnancy. Therefore, the goal of this study is to assess the effect of gestational arsenic exposure on maternal
cardiovascular health during and after pregnancy through the following specific aims: 1) define effects of
gestational arsenic exposure on the maternal heart during and after pregnancy, 2) define the role of estrogen
disruption in arsenic-induced maternal cardiac pathology in pregnancy, and 3) assess whether one-carbon
metabolism supplementation mitigates arsenic-induced maternal cardiac pathology in pregnancy. Across all
aims, we will also leverage a large biorepository from a well-characterized cohort of women in Bangladesh who
experienced arsenic exposure during pregnancy, providing a unique opportunity to evaluate biomarkers of
cardiovascular health in this population and assess the translational relevance of findings from our preclinical
mouse studies. If completed successfully, this proposal will provide important foundational information regarding
the effect of gestational arsenic exposure on the maternal heart during and after pregnancy and establish critical
biomarkers that translational scientists can use to inform future human study design, establish risk profiles, and
develop policy and actionable intervention points to improve cardiovascular outcomes for vulnerable pregnant
women.document fetched 2026-09-06 02:47