Theses and Dissertations from DePaul University

Date of Award

1-21-2026

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Science

College

College of Science and Health

First Advisor

Margaret Bell

Abstract

Per-/polyfluoroalkyl substances (PFAS) are persistent organic pollutants commonly used in non-stick, oil-resistant, and water-proof food packaging as well as textiles; they are detected in more than 99% of human serum. Perfluorooctane sulfonic acid (PFOS), one of the most ubiquitous PFAS, is associated with altered lipid metabolism, immunotoxicity, and neurodevelopmental disorders. These outcomes all implicate microglia, resident macrophages in the brain critical for development and sensitive to lipid signaling, as key mediators of toxicity. However, developmental effects of PFOS on microglia are not well-characterized, nor is it clear how PFOS alters microglial inflammatory responses. We hypothesized that early-life PFOS exposure alters microglial responses to secondary inflammatory challenges later in life. To test this, pregnant Sprague Dawley dams were exposed to PFOS (0.5 ug/kg BW/day ) or vehicle daily via ‘Nilla wafers from gestation until offspring weaning. Offspring were weighed daily and development was monitored until euthanasia in adolescence. Two hours before euthanasia, adolescent offspring were given an inflammatory challenge (lipopolysaccharide, LPS, 0.5 mg/kg BW i.p.); sickness behaviors were monitored for two hours until euthanasia. Brains were collected and microglia were isolated from one cerebral hemisphere using CD11b+ magnetic beads. RNA was isolated from both the microglial and non-microglial pools. Animals exposed to PFOS exhibited reduced weight gain from P7 to P21 relative to their P1 weight. Conversely, PFOS-exposed animals had greater weight gain after weaning, from P28 to P42 relative to P21. Because ‘catch-up’ weight gain in early development is linked to metabolic dysfunction in humans, lipid and thyroid hormone analyses are planned. Targeted gene expression analysis of non-microglial cells did not detect PFOS effects on expression of genes related to thyroid (Dio2), dopamine (Drd1a), and calcium (CamkIIa) signaling or on synaptic regulation (Syt). While previously shown to be altered by PFOS exposure, the lack of PFOS-mediated alterations in expression of these genes in the current study may reflect region-specific responses undetectable in our whole brain samples. Unbiased analyses of the CD11b+ microglial transcriptome indicates widespread gene upregulation in response to LPS. Gene Set Enrichment Analysis show PFOS exposure enriches pathways related to inflammation and cell metabolism depending sex and LPS challenge. Knowledge generated in these studies highlights the need to design toxicology studies that test for effects of contaminants in a range of contexts. It also affirms microglia as a potential mechanism by which PFOS alters neurodevelopment, raising the possibility for exposures to interact with other environmental challenges known to engage the neuroimmune system.

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