Exposure of mice to environmentally relevant per- and polyfluoroalkyl substances (PFAS) alters the sperm epigenome

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

doi:10.1038/s42003-025-08865-4

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Exposure of mice to environmentally relevant per- and polyfluoroalkyl substances (PFAS) alters the sperm epigenome

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Exposure of mice to environmentally relevant per- and polyfluoroalkyl substances (PFAS) alters the sperm epigenome

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, …

Communications Biology, Vol.8, pp.1-20

2025

DOI: https://doi.org/10.1038/s42003-025-08865-4

PMID: 41152411

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Abstract

experimental models of disease

spermatogenesis

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.

Details

Title: Exposure of mice to environmentally relevant per- and polyfluoroalkyl substances (PFAS) alters the sperm epigenome
Authors: Leah Gillespie - Hunter Medical Research Institute
Jacinta H. Martin (Corresponding Author) - University of Newcastle Australia
Amanda L. Anderson - University of Newcastle Australia
Ilana R. Bernstein - University of Newcastle Australia
Simone J. Stanger - University of Newcastle Australia
Natalie A. Trigg - University of Newcastle Australia
John E. Schjenken - University of Newcastle Australia
Anne-Louise Gannon - Hunter Medical Research Institute
Shanu Parameswaran - Hunter Medical Research Institute
Shannon P. Smyth - University of Newcastle Australia
Colin C. Conine - Children's Hospital of Philadelphia
Reena Desai - Anzac Research Institute
David J. Handelsman - Anzac Research Institute
Geoffry N. De Iuliis - University of Newcastle Australia
Andrew L. Eamens - University of the Sunshine Coast, Queensland, School of Health - Biomedicine
Matthew D. Dun - Hunter Medical Research Institute
Brett D. Turner - University of Technology Sydney
Shaun D. Roman - New South Wales Department of Health
Mark P. Green - The University of Melbourne
Brett Nixon - University of Newcastle Australia
Publication details: Communications Biology, Vol.8, pp.1-20
Publisher: Nature Publishing Group
Date published: 2025
DOI: 10.1038/s42003-025-08865-4
ISSN: 2399-3642
PMID: 41152411
Copyright note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Data Availability: The gene expression datasets generated and analyzed during the current study are available in the Gene Expression Omnibus repository with accession number GSE271479. Further data that support the findings of this study, including the numerical source data for graphs and charts are available in the Supplementary Data. Any additional information is available from the corresponding author upon reasonable request.
Grants: Utilising male fertility as a biomarker of health to understand the biological effects of PFAS, 1189415, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Mechanistic and translational studies to improve the outcomes of high-risk paediatric cancers , 1173892, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Mechanistic and translational studies in male reproductive health , 1154837, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Australian Government Research Training Program (RTP) Scholarship, RTP, Department of Education (Australia, Canberra)
Organisation Unit: School of Health - Biomedicine
Language: English
Record Identifier: 991175217002621
Output Type: Journal article

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