Accumulation of perfluorooctanoic acid in intestine and lung tissues and its effect on gene expression across multiple pathways

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.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Ahmad, Saeed

Contributors dc:contributor

• Irudayaraj, Joseph

• PFOA, Bioaccumulation, Gene expression

Statement dc:rights

• Copyright 2025 Saeed Ahmad

Language dc:language

en

Handle dc:identifier

https://hdl.handle.net/2142/132641

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/132641