Long-term effects of prenatal arsenic exposure from gestational day 9 to birth on lung, heart, and immune outcomes in the C57BL/6 mouse model

Kristal A. Rychlik, Emily J. Illingworth, Ian F. Sanchez, Sarah E. Attreed, Prithvi Sinha, Kevin M. Casin, Nicole Taube, Jeff Loube, Rokeya Tasneen, Raihan Kabir, Eric Nuermberger, Wayne Mitzner, Mark J. Kohr, Fenna C.M. Sillé

Research output: Contribution to journalArticlepeer-review


Prenatal arsenic exposure is a major public health concern, associated with altered birth outcomes and increased respiratory disease risk. However, characterization of the long-term effects of mid-pregnancy (second trimester) arsenic exposure on multiple organ systems is scant. This study aimed to characterize the long-term impact of mid-pregnancy inorganic arsenic exposure on the lung, heart, and immune system, including infectious disease response using the C57BL/6 mouse model. Mice were exposed from gestational day 9 till birth to either 0 or 1000 µg/L sodium (meta)arsenite in drinking water. Male and female offspring assessed at adulthood (10–12 weeks of age) did not show significant effects on recovery outcomes after ischemia reperfusion injury but did exhibit increased airway hyperresponsiveness compared to controls. Flow cytometric analysis revealed significantly greater total numbers of cells in arsenic-exposed lungs, lower MHCII expression in natural killer cells, and increased percentages of dendritic cell populations. Activated interstitial (IMs) and alveolar macrophages (AMs) isolated from arsenic-exposed male mice produced significantly less IFN-γ than controls. Conversely, activated AMs from arsenic-exposed females produced significantly more IFN-γ than controls. Although systemic cytokine levels were higher upon Mycobacterium tuberculosis (Mtb) infection in prenatally arsenic-exposed offspring there was no difference in lung Mtb burden compared to controls. This study highlights significant long-term impacts of prenatal arsenic exposure on lung and immune cell function. These effects may contribute to the elevated risk of respiratory diseases associated with prenatal arsenic exposure in epidemiology studies and point to the need for more research into mechanisms driving these maintained responses.

Original languageEnglish (US)
Pages (from-to)17-32
Number of pages16
JournalToxicology Letters
StatePublished - Jul 1 2023


  • Animal model
  • Arsenic
  • Developmental (or pregnancy)
  • Immunotoxicity

ASJC Scopus subject areas

  • Toxicology


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