Exposure of mice to environmentally relevant per- and polyfluoroalkyl substances (PFAS) alters the sperm epigenome
Year: 2025
Type: article
Abstract: Per- and polyfluoroalkyl substances (PFAS) are a large group of persistent synthetic chemicals and ubiquitous environmental contaminants. Mounting evidence demonstrates that PFAS can bioaccumulate and induce adverse health outcomes, including compromising male reproduction. Despite this, the mechanisms by which PFAS elicits these effects remain unclear. Here, we investigate how an environmentally relevant PFAS cocktail impacts the reproductive function of male Swiss CD1 mice. Following twelve weeks of continuous exposure, we collected blood samples for hormone and PFAS quantification and processed reproductive tissues and spermatozoa for histological and functional assessment. PFAS exposure significantly reduced the rate of daily sperm production, likely due to decreased circulating testosterone and dihydrotestosterone. Further, PFAS-exposed spermatozoa displayed marked alterations to their small non-coding RNA profile, which were linked to dysregulation of early-embryonic gene expression. Notably, these changes occured without significant alteration in sperm viability, motility, or the ability to undergo capacitation or support embryonic development. These findings provide new mechanistic insight into how PFAS exposure impacts male reproductive health.
Source: Communications Biology
Authors: Leah Gillespie, Jacinta H. Martin, Amanda L. Anderson, Ilana R. Bernstein, Simone J. Stanger, Natalie A. Trigg, John E. Schjenken, Anne-Louise Gannon, Shanu Parameswaran, Shannon P. Smyth, Colin C. Conine, Reena Desai, David J. Handelsman, Geoffry N. De Iuliis, Andrew L. Eamens, Matthew D. Dun, Brett D. Turner, Shaun D. Roman, Mark P. Green, Brett Nixon
Institutions: Hunter Medical Research Institute, University of Newcastle Australia, Children's Hospital of Philadelphia, The University of Melbourne, University of Pennsylvania, The University of Sydney, Anzac Research Institute, University of the Sunshine Coast, University of Technology Sydney, NSW Health Pathology
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Children's Hospital of Philadelphia, University of Pennsylvania, Australian Government, NSW Health Pathology, Hunter Medical Research Institute, University of Technology Sydney, University of the Sunshine Coast, Perelman School of Medicine, University of Pennsylvania, Medical Research Council, National Health and Medical Research Council, Faculty of Science, University of Melbourne, National Institute of Environmental Health Sciences
Awards: Mechanistic and translational studies to improve the outcomes of high-risk paediatric cancers, Mechanistic and translational studies in male reproductive health, Utilising male fertility as a biomarker of health to understand the biological effects of PFAS, Center of Excellence in Environmental Toxicology
OpenAlex ID: W4415611797