Accumulation of perfluorooctanoic acid in intestine and lung tissues and its effect on gene expression across multiple pathways
Ahmad, Saeed
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Permalink
https://hdl.handle.net/2142/132641
Description
Title
Accumulation of perfluorooctanoic acid in intestine and lung tissues and its effect on gene expression across multiple pathways
Author(s)
Ahmad, Saeed
Issue Date
2025-11-19
Director of Research (if dissertation) or Advisor (if thesis)
Irudayaraj, Joseph
Department of Study
Bioengineering
Discipline
Bioengineering
Degree Granting Institution
University of Illinois Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(s)
PFOA, Bioaccumulation, Gene expression
Abstract
Perfluorooctanoic acid (PFOA) a most common Per- and polyfluoroalkyl substances (PFAS) is a ubiquitous and persistent environmental pollutant. Humans are exposed to it via drinking water, food and airborne dust particulates. Due to its stable nature and slow biological clearance, it remains for long in the human systems and even concentrations increase upon continued exposure and that’s why it poses major health concerns. Several studies including epidemiological, animal model and invitro has linked PFOA to different organs toxicities. Although the gastrointestinal tract and lung tissues are primary organs exposed to PFOA, they are not well explored for its toxicities.
Herein we utilized the CD1 male mice model to get exposed to different concentrations of PFOA via oral dosing. After daily administration for 10 days intestinal (small intestine and colon) and lung tissues were harvested. PFOA concentrations were quantified in all collected organs using LC-MS, followed by gene expression analysis targeting epigenetic regulators (Dnmt and Tet) in these tissues, with additional focus on tight junction genes in intestinal tissue and genes involved in pathogen infection pathways in lung.
PFOA has accumulated across all tissues which increased proportionally in a dose dependent manner with notably higher concentrations in the lungs compared to intestinal tissue. Dnmt genes were downregulated in both small intestine and lungs tissue where Tet genes expressions have gene and tissue specific variability across different organs. In intestinal tissue the tight junction genes expression was more dysregulated in small intestine compared to colon. In lung tissue Ace2 and Tmprss2 genes were upregulated where CpG islands in regulatory region of Tmprss2 exhibit significant hypomethylation patterns. Collectively, these findings suggest that PFOA is potentially contributing to the tissue specific toxicological effects.
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