Gene expression patterns associated with PFOA exposure in Czech young men and women

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Authors

RUDZANOVÁ Barbora THON Vojtěch VESPALCOVÁ Hana MARTYNIUK Christopher J. PILER Pavel ZVONAŘ Martin KLÁNOVÁ Jana BLÁHA Luděk ADAMOVSKÝ Ondřej

Year of publication 2024
Type Article in Periodical
Magazine / Source Environment International
MU Faculty or unit

Faculty of Science

Citation
Web https://www.sciencedirect.com/science/article/pii/S0160412024004653?via%3Dihub
Doi http://dx.doi.org/10.1016/j.envint.2024.108879
Keywords Perfluorooctanoic acid; Peripheral blood mononuclear cells; Transcriptome; Sex differences; Enrichment analysis
Attached files
Description Perfluorooctanoic acid (PFOA), a member of per- and polyfluoroalkyl substances (PFASs), has been widely used in manufacturing for decades. Currently, PFOA is strictly regulated, but due to its high stability and persistence, it is detected in both environmental as well as in human matrices. To elucidate mechanisms of PFOA toxicity in humans, we determined the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMC) responding to PFOA exposure in a sex-stratified analysis. This work employed samples from 145 female and 143 male participants of the CELSPAC: YA study to characterize PFOA-associated transcripts in a broader context using computational analysis. PFOA-associated gene expression differed significantly between men and women, as only 2 % of mapped genes were expressed in both sexes. Disease-specific enrichment analysis revealed cancer and immune-related disease terms as those most enriched in male and female populations. Patterns of enriched terms within the gene set enrichment analysis indicated three main targets of PFOA toxicity: i) lipid metabolism for women; ii) cell cycle regulation for men; and iii) immune system response for both sexes. In summary, our genome-wide transcriptomics analysis described sex-specific differences in PFOA-associated gene expression and provided evidence about biological pathways underlying PFOA toxicity in humans.
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