2023 Annual Meeting Report: PFAS Toxicity Platform Talks Prove Popular

By Samantha Hall posted 05-04-2023 11:14


The Platform Session “Mechanisms of PFAS Toxicity” provided plenty of great science on per- and polyfluoroalkyl substances to a packed audience during the 2023 SOT Annual Meeting and ToxExpo. Following on the heels of the US Environmental Protection Agency (US EPA) announcement on March 14 of draft drinking water maximum contaminant levels for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), this popular Platform Session was filled with great PFAS science from nine presenters.

Daniel Villeneuve, US EPA, opened the session with his talk on the estrogenic activity of PFAS. Four PFAS, which had been previously identified as estrogenic via in vitro screening, were tested for their in vivo estrogenic activity in fish. These PFAS (consisting of PFOA and three diols: FC10-diol, FC8-diol, and FC8-DOD) were found to elicit estrogenic responses in male fathead minnows. One notable finding was that FC10-diol was more potent than other PFAS during in vivo testing than in vitro screening. Dr. Villeneuve demonstrated that this in vivo result was driven by FC10-diol’s greater bioconcentration.

Next, Tomoko Ishikawa, University of Michigan, explored the sex-specific effects of PFOA on human-induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs). In male-derived hiPSCs, she found that PFOA affected cell expansion and decreased TET2 expression and cardiac troponin T (cTnT)positive cells. These findings may help to explain the different sex-specific epigenetic modifications that occur during developmental chemical exposure, which could lead to later-life cardiovascular disease.

Dakota Robarts, University of Kansas Medical Center, presented his work on PFAS-induced hepatotoxicity in a novel humanized mouse model. This liver-chimeric mouse model lacks several enzymes, leading to the death of mouse hepatocytes which are then repopulated with human hepatocytes via intrasplenic injection. The mice were then exposed to drinking water with PFOA, PFOS, and GenX for 28 days. Subsequent RNA-sequencing and pathway analysis illustrated that PFAS altered the expression of circadian rhythm genes such as NR1D1.

Continuing with humanized mice, Greylin Nielsen, Boston University, discussed the effect of PFOA on hepatic lipids in a mouse model that expresses human PPAR-alpha. When these mice were treated with PFOA, the hepatic lipid profiles changed. Transcriptomic analysis demonstrated that the lipid profile changes occurred through multiple transcription factors, not just PPAR-alpha.

Emily Kaye, University of Rhode Island, discussed her work on PFOS in an albumin-deficient mouse model. In wild-type mice, PFOS is typically bound to albumin protein in the blood, with some free PFOS distributing to other tissues and organs. Kaye found that in albumin-deficient mice, PFOS concentrations were lower in blood and higher in liver; this finding demonstrated that albumin is critical for PFOS distribution in vivo.

Marjorie Marin, University of Massachusetts Amherst, presented on the effect of PFOS on insulin biosynthesis in pancreatic cells. She found that PFOS exposure increased reactive oxygen species (ROS) generation, decreased insulin secretion, and increased the aggregation and misfolding of proinsulin.

Kendra Clark, University of Nebraska, demonstrated how an environmentally-relevant PFAS mixture impacted primary human granulosa cells from women undergoing in vitro fertilization. Granulosa cells are found in the follicles of ovaries and produce important sex steroids and hormones necessary for fertility. Exposure to a mixture of PFOA, PFOS, and PFHxS was found to induce proliferation, alter steroid hormone synthesis, and alter the granulosa cell transcriptome.

Brittany Rickard, University of North Carolina at Chapel Hill, presented research on PFAS and ovarian cancer—a particularly lethal cancer. PFAS were found to induce resistance to platinum chemotherapy in ovarian cancer, which would make cancer treatment more difficult. Rickard found that PFAS altered the oxidative profiles in ovarian cancer cells, indicating that mitochondria may be the target of PFAS-induced platinum resistance.

Lastly, Laimar Garmo, Wayne State University, closed out the session with his research on bone marrow and metastatic prostate cancer growth. He found that PFHxS-driven adipogenesis in bone marrow was partially mediated through the PPAR-gamma receptor and is important in the growth and metastasis of prostate cancer.

This Platform Session was chaired by Rebecca McCullough, University of Colorado Anschutz Medical Campus, and Alicia Timme-Laragy, University of Massachusetts Amherst.

This blog reports on the Platform Session titled “Mechanisms of PFAS Toxicity” that was held during the 2023 SOT Annual Meeting and ToxExpo. An on-demand recording of this session is available for meeting registrants on the SOT Online Planner and SOT Event App.

This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email SOT Headquarters.