{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:38:15Z","timestamp":1792103895607,"version":"4.4.0"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1189415"],"award-info":[{"award-number":["APP1189415"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1189415"],"award-info":[{"award-number":["APP1189415"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1189415"],"award-info":[{"award-number":["APP1189415"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1173892"],"award-info":[{"award-number":["APP1173892"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1189415"],"award-info":[{"award-number":["APP1189415"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1189415"],"award-info":[{"award-number":["APP1189415"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1189415"],"award-info":[{"award-number":["APP1189415"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1154837"],"award-info":[{"award-number":["APP1154837"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Defeat DIPG ChadTough New Investigator Fellowship"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Per- and polyfluoroalkyl substances (PFAS) are a large group of\u00a0persistent 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\u00a0by 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.<\/jats:p>","DOI":"10.1038\/s42003-025-08865-4","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:03:57Z","timestamp":1761645837000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Exposure of mice to environmentally relevant per- and polyfluoroalkyl substances (PFAS) alters the sperm epigenome"],"prefix":"10.1038","volume":"8","author":[{"given":"Leah","family":"Gillespie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0876-5150","authenticated-orcid":false,"given":"Jacinta H.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana R.","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone J.","family":"Stanger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie A.","family":"Trigg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-6160","authenticated-orcid":false,"given":"John E.","family":"Schjenken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Louise","family":"Gannon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanu","family":"Parameswaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon P.","family":"Smyth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-0463","authenticated-orcid":false,"given":"Colin C.","family":"Conine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-7476","authenticated-orcid":false,"given":"David J.","family":"Handelsman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6978-6123","authenticated-orcid":false,"given":"Geoffry N.","family":"De Iuliis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6327-3618","authenticated-orcid":false,"given":"Andrew L.","family":"Eamens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9063-5370","authenticated-orcid":false,"given":"Matthew D.","family":"Dun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett D.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7758-7757","authenticated-orcid":false,"given":"Shaun D.","family":"Roman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2745-8188","authenticated-orcid":false,"given":"Brett","family":"Nixon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"8865_CR1","unstructured":"Kissa, E. Fluorinated Surfactants and Repellents 2nd edn (American Chemical Society, 2001)."},{"key":"8865_CR2","unstructured":"Organisation for Economic Co-operation and Development. OECD accession review of Costa Rica in the field of chemicals: Summary report. ENV\/JM\/WRPR(2019)53\/FINAL. (OECD Publishing, Paris, 2020)."},{"key":"8865_CR3","doi-asserted-by":"crossref","unstructured":"Banks, R. E., Smart, B. E. & Tatlow, J. Organofluorine chemistry: principles and commercial applications (Springer Science & Business Media, 1994).","DOI":"10.1007\/978-1-4899-1202-2"},{"key":"8865_CR4","unstructured":"Kissa E. Fluorinated surfactants and repellents (CRC Press, 2001)."},{"key":"8865_CR5","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1002\/ieam.258","volume":"7","author":"RC Buck","year":"2011","unstructured":"Buck, R. C. et al. Perfluoroalkyl and polyfluoroalkyl substances in the environment: terminology, classification, and origins. Integr. Environ. Assess. Manag. 7, 513\u2013541 (2011).","journal-title":"Integr. Environ. Assess. Manag."},{"key":"8865_CR6","doi-asserted-by":"publisher","first-page":"7954","DOI":"10.1021\/es2011622","volume":"45","author":"AB Lindstrom","year":"2011","unstructured":"Lindstrom, A. B., Strynar, M. J. & Libelo, E. L. Polyfluorinated compounds: past, present, and future. Environ. Sci. Technol. 45, 7954\u20137961 (2011).","journal-title":"Environ. Sci. Technol."},{"key":"8865_CR7","doi-asserted-by":"publisher","first-page":"154a","DOI":"10.1021\/es012317k","volume":"35","author":"R Renner","year":"2001","unstructured":"Renner, R. Growing concern over perfluorinated chemicals. Environ. Sci. Technol. 35, 154a\u2013160aa (2001).","journal-title":"Environ. Sci. Technol."},{"key":"8865_CR8","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1021\/es902444r","volume":"44","author":"CD Vecitis","year":"2010","unstructured":"Vecitis, C. D. et al. Sonochemical degradation of perfluorooctanesulfonate in aqueous film-forming foams. Environ. Sci. Technol. 44, 432\u2013438 (2010).","journal-title":"Environ. Sci. Technol."},{"key":"8865_CR9","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1021\/acs.estlett.6b00260","volume":"3","author":"XC Hu","year":"2016","unstructured":"Hu, X. C. et al. Detection of poly- and perfluoroalkyl substances (PFASs) in U.S. drinking water linked to industrial sites, military fire training areas, and wastewater treatment plants. Environ. Sci. Technol. Lett. 3, 344\u2013350 (2016).","journal-title":"Environ. Sci. Technol. Lett."},{"key":"8865_CR10","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1097\/01.jom.0000232486.07658.74","volume":"48","author":"EA Emmett","year":"2006","unstructured":"Emmett, E. A. et al. Community exposure to perfluorooctanoate: relationships between serum concentrations and exposure sources. J. Occup. Environ. Med. 48, 759\u2013770 (2006).","journal-title":"J. Occup. Environ. Med."},{"key":"8865_CR11","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1021\/acs.est.6b04806","volume":"51","author":"Z Wang","year":"2017","unstructured":"Wang, Z., DeWitt, J. C., Higgins, C. P. & Cousins, I. T. A never-ending story of per- and polyfluoroalkyl substances (PFASs)? Environ. Sci. Technol. 51, 2508\u20132518 (2017).","journal-title":"Environ. Sci. Technol."},{"key":"8865_CR12","doi-asserted-by":"publisher","first-page":"14062","DOI":"10.1021\/es403094q","volume":"47","author":"AC Blaine","year":"2013","unstructured":"Blaine, A. C. et al. Uptake of perfluoroalkyl acids into edible crops via land applied biosolids: field and greenhouse studies. Environ. Sci. Technol. 47, 14062\u201314069 (2013).","journal-title":"Environ. Sci. Technol."},{"key":"8865_CR13","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1289\/ehp.0800379","volume":"117","author":"SJ Frisbee","year":"2009","unstructured":"Frisbee, S. J. et al. The C8 health project: design, methods, and participants. Environ. Health Perspect. 117, 1873\u20131882 (2009).","journal-title":"Environ. Health Perspect."},{"key":"8865_CR14","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.envint.2017.06.007","volume":"106","author":"RR Worley","year":"2017","unstructured":"Worley, R. R. et al. Per- and polyfluoroalkyl substances in human serum and urine samples from a residentially exposed community. Environ. Int. 106, 135\u2013143 (2017).","journal-title":"Environ. Int."},{"key":"8865_CR15","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1080\/10408444.2016.1182117","volume":"46","author":"CC Bach","year":"2016","unstructured":"Bach, C. C. et al. Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: a systematic review. Crit. Rev. Toxicol. 46, 735\u2013755 (2016).","journal-title":"Crit. Rev. Toxicol."},{"key":"8865_CR16","doi-asserted-by":"publisher","first-page":"799043","DOI":"10.3389\/fendo.2021.799043","volume":"12","author":"L Calvert","year":"2022","unstructured":"Calvert, L. et al. Assessment of the emerging threat posed by perfluoroalkyl and polyfluoroalkyl substances to male reproduction in humans. Front. Endocrinol. 12, 799043 (2022).","journal-title":"Front. Endocrinol."},{"key":"8865_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2020.152565","volume":"443","author":"BE Blake","year":"2020","unstructured":"Blake, B. E. & Fenton, S. E. Early life exposure to per- and polyfluoroalkyl substances (PFAS) and latent health outcomes: a review including the placenta as a target tissue and possible driver of peri- and postnatal effects. Toxicology 443, 152565 (2020).","journal-title":"Toxicology"},{"key":"8865_CR18","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1289\/ehp.1306615","volume":"121","author":"V Barry","year":"2013","unstructured":"Barry, V., Winquist, A. & Steenland, K. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ. Health Perspect. 121, 1313\u20131318 (2013).","journal-title":"Environ. Health Perspect."},{"key":"8865_CR19","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1289\/ehp.1307621","volume":"123","author":"GM Louis","year":"2015","unstructured":"Louis, G. M. et al. Perfluorochemicals and human semen quality: the LIFE study. Environ. Health Perspect. 123, 57\u201363 (2015).","journal-title":"Environ. Health Perspect."},{"key":"8865_CR20","doi-asserted-by":"publisher","DOI":"10.1289\/EHP4431","volume":"127","author":"Y Pan","year":"2019","unstructured":"Pan, Y. et al. Profiles of emerging and legacy per-\/polyfluoroalkyl substances in matched serum and semen samples: new implications for human semen quality. Environ. Health Perspect. 127, 127005 (2019).","journal-title":"Environ. Health Perspect."},{"key":"8865_CR21","doi-asserted-by":"publisher","first-page":"2532","DOI":"10.1093\/humrep\/des185","volume":"27","author":"G Toft","year":"2012","unstructured":"Toft, G. et al. Exposure to perfluorinated compounds and human semen quality in arctic and European populations. Hum. Reprod. 27, 2532\u20132540 (2012).","journal-title":"Hum. Reprod."},{"key":"8865_CR22","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1093\/humrep\/des425","volume":"28","author":"UN Joensen","year":"2013","unstructured":"Joensen, U. N. et al. PFOS (perfluorooctanesulfonate) in serum is negatively associated with testosterone levels, but not with semen quality, in healthy men. Hum. Reprod. 28, 599\u2013608 (2013).","journal-title":"Hum. Reprod."},{"key":"8865_CR23","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.reprotox.2011.05.024","volume":"33","author":"JH Raymer","year":"2012","unstructured":"Raymer, J. H. et al. Concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and their associations with human semen quality measurements. Reprod. Toxicol. 33, 419\u2013427 (2012).","journal-title":"Reprod. Toxicol."},{"key":"8865_CR24","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1289\/ehp.0800517","volume":"117","author":"UN Joensen","year":"2009","unstructured":"Joensen, U. N. et al. Do perfluoroalkyl compounds impair human semen quality? Environ. Health Perspect. 117, 923\u2013927 (2009).","journal-title":"Environ. Health Perspect."},{"key":"8865_CR25","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1007\/s10529-009-0065-7","volume":"31","author":"T Yamamoto","year":"2009","unstructured":"Yamamoto, T. et al. Classification of FABP isoforms and tissues based on quantitative evaluation of transcript levels of these isoforms in various rat tissues. Biotechnol. Lett. 31, 1695\u20131701 (2009).","journal-title":"Biotechnol. Lett."},{"key":"8865_CR26","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1002\/etc.199","volume":"29","author":"MW Woodcroft","year":"2010","unstructured":"Woodcroft, M. W. et al. Experimental characterization of the mechanism of perfluorocarboxylic acids\u2019 liver protein bioaccumulation: the key role of the neutral species. Environ. Toxicol. Chem. 29, 1669\u20131677 (2010).","journal-title":"Environ. Toxicol. Chem."},{"key":"8865_CR27","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/s41585-022-00640-y","volume":"19","author":"ND Burke","year":"2022","unstructured":"Burke, N. D. et al. Male infertility and somatic health - insights into lipid damage as a mechanistic link. Nat. Rev. Urol. 19, 727\u2013750 (2022).","journal-title":"Nat. Rev. Urol."},{"key":"8865_CR28","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.chemosphere.2019.04.139","volume":"229","author":"BD Turner","year":"2019","unstructured":"Turner, B. D., Sloan, S. W. & Currell, G. R. Novel remediation of per-and polyfluoroalkyl substances (PFASs) from contaminated groundwater using Cannabis Sativa L.(hemp) protein powder. Chemosphere 229, 22\u201331 (2019).","journal-title":"Chemosphere"},{"key":"8865_CR29","doi-asserted-by":"crossref","unstructured":"Calvert, L. et al. Assessment of the impact of direct in vitro PFAS treatment on mouse spermatozoa. Reprod. Fertil. 5, e230087 (2024).","DOI":"10.1530\/RAF-23-0087"},{"key":"8865_CR30","unstructured":"NHMRC. NHMRC Review of PFAS in Australian drinking water. National Medical Research Council. Available from https:\/\/www.nhmrc.gov.au\/health-advice\/environmental-health\/water\/PFAS-review (2025)."},{"key":"8865_CR31","unstructured":"EPA. US Environmental Protection Agency, Final PFAS National Primary Drinking Water Regulation. Available from https:\/\/www.epa.gov\/sdwa\/and-polyfluoroalkyl-substances-pfas (2024)."},{"key":"8865_CR32","unstructured":"EU. European Union Directive (EU) 2020\/2184 of the European Parliament and of the Council of 16 December 2020 on the quality of water intended for human consumption (recast). Available from https:\/\/eur-lex.europa.eu\/eli\/dir\/2020\/2184\/oj (2020)."},{"key":"8865_CR33","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1242\/jcs.02704","volume":"119","author":"L Cotton","year":"2006","unstructured":"Cotton, L. et al. FGFR-1 signaling is involved in spermiogenesis and sperm capacitation. J. Cell Sci. 119, 75\u201384 (2006).","journal-title":"J. Cell Sci."},{"key":"8865_CR34","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1530\/jrf.0.0540103","volume":"54","author":"GW Robb","year":"1978","unstructured":"Robb, G. W., Amann, R. P. & Killian, G. J. Daily sperm production and epididymal sperm reserves of pubertal and adult rats. Reproduction 54, 103\u2013107 (1978).","journal-title":"Reproduction"},{"key":"8865_CR35","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.devcel.2018.06.024","volume":"46","author":"CC Conine","year":"2018","unstructured":"Conine, C. C., Sun, F., Song, L., Rivera-P\u00e9rez, J. A. & Rando, O. J. Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice. Dev. Cell 46, 470\u201380.e3 (2018).","journal-title":"Dev. Cell"},{"key":"8865_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109787","volume":"37","author":"NA Trigg","year":"2021","unstructured":"Trigg, N. A. et al. Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development. Cell Rep. 37, 109787 (2021).","journal-title":"Cell Rep."},{"key":"8865_CR37","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","volume":"120","author":"BP Lewis","year":"2005","unstructured":"Lewis, B. P., Burge, C. B. & Bartel, D. P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15\u201320 (2005).","journal-title":"Cell"},{"key":"8865_CR38","doi-asserted-by":"publisher","first-page":"e05005","DOI":"10.7554\/eLife.05005","volume":"4","author":"V Agarwal","year":"2015","unstructured":"Agarwal, V., Bell, G. W., Nam, J. W. & Bartel, D. P. Predicting effective microRNA target sites in mammalian mRNAs. Elife 4, e05005 (2015).","journal-title":"Elife"},{"key":"8865_CR39","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.reprotox.2012.02.008","volume":"33","author":"IO Specht","year":"2012","unstructured":"Specht, I. O. et al. Sperm DNA integrity in relation to exposure to environmental perfluoroalkyl substances - a study of spouses of pregnant women in three geographical regions. Reprod. Toxicol. 33, 577\u2013583 (2012).","journal-title":"Reprod. Toxicol."},{"key":"8865_CR40","doi-asserted-by":"crossref","DOI":"10.2903\/j.efsa.2021.e190101","volume":"19","author":"S More","year":"2021","unstructured":"More, S. et al. Opinion on the impact of non-monotonic dose responses on EFSA\u2019s human health risk assessments. EFSA J. 19, e06877 (2021).","journal-title":"EFSA J."},{"key":"8865_CR41","doi-asserted-by":"publisher","DOI":"10.1186\/1476-069X-14-13","volume":"14","author":"F Lagarde","year":"2015","unstructured":"Lagarde, F. et al. Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment. Environ. Health 14, 13 (2015).","journal-title":"Environ. Health"},{"key":"8865_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2020.110346","volume":"192","author":"SK Park","year":"2021","unstructured":"Park, S. K., Ding, N. & Han, D. Perfluoroalkyl substances and cognitive function in older adults: should we consider non-monotonic dose-responses and chronic kidney disease? Environ. Res. 192, 110346 (2021).","journal-title":"Environ. Res."},{"key":"8865_CR43","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/s41370-023-00529-x","volume":"33","author":"L Dunder","year":"2023","unstructured":"Dunder, L., Salihovic, S., Elmst\u00e5hl, S., Lind, P. M. & Lind, L. Associations between per- and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden. J. Expo. Sci. Environ. Epidemiol. 33, 748\u2013756 (2023).","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"8865_CR44","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41370-022-00464-3","volume":"33","author":"SY Gui","year":"2023","unstructured":"Gui, S. Y. et al. Association between per- and polyfluoroalkyl substances exposure and risk of diabetes: a systematic review and meta-analysis. J. Expo. Sci. Environ. Epidemiol. 33, 40\u201355 (2023).","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"8865_CR45","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.etap.2014.07.003","volume":"38","author":"Y Wang","year":"2014","unstructured":"Wang, Y. et al. Investigation on the relationship between bioconcentration factor and distribution coefficient based on class-based compounds: the factors that affect bioconcentration. Environ. Toxicol. Pharmacol. 38, 388\u2013396 (2014).","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"8865_CR46","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/0041-008X(92)90116-A","volume":"113","author":"JC Cook","year":"1992","unstructured":"Cook, J. C., Murray, S. M., Frame, S. R. & Hurtt, M. E. Induction of Leydig cell adenomas by ammonium perfluorooctanoate: a possible endocrine-related mechanism. Toxicol. Appl. Pharm. 113, 209\u2013217 (1992).","journal-title":"Toxicol. Appl. Pharm."},{"key":"8865_CR47","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.envres.2014.07.006","volume":"134","author":"S L\u00f3pez-Doval","year":"2014","unstructured":"L\u00f3pez-Doval, S., Salgado, R., Pereiro, N., Moyano, R. & Lafuente, A. Perfluorooctane sulfonate effects on the reproductive axis in adult male rats. Environ. Res. 134, 158\u2013168 (2014).","journal-title":"Environ. Res."},{"key":"8865_CR48","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1095\/biolreprod.110.089219","volume":"84","author":"HT Wan","year":"2011","unstructured":"Wan, H. T. et al. Testicular signaling is the potential target of perfluorooctanesulfonate-mediated subfertility in male mice. Biol. Reprod. 84, 1016\u20131023 (2011).","journal-title":"Biol. Reprod."},{"key":"8865_CR49","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.etap.2016.05.025","volume":"45","author":"J-H Qu","year":"2016","unstructured":"Qu, J.-H. et al. Perfluorooctane sulfonate-induced testicular toxicity and differential testicular expression of estrogen receptor in male mice. Environ. Toxicol. Pharmacol. 45, 150\u2013157 (2016).","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"8865_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2020.115330","volume":"266","author":"Q Cui","year":"2020","unstructured":"Cui, Q. et al. Exposure to per- and polyfluoroalkyl substances (PFASs) in serum versus semen and their association with male reproductive hormones. Environ. Pollut. 266, 115330 (2020).","journal-title":"Environ. Pollut."},{"key":"8865_CR51","doi-asserted-by":"publisher","first-page":"4226","DOI":"10.1096\/fj.12-224048","volume":"27","author":"T Fullston","year":"2013","unstructured":"Fullston, T. et al. Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB J. 27, 4226\u20134243 (2013).","journal-title":"FASEB J."},{"key":"8865_CR52","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/s41586-024-07472-3","volume":"630","author":"A Tomar","year":"2024","unstructured":"Tomar, A. et al. Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs. Nature 630, 720\u2013727 (2024).","journal-title":"Nature"},{"key":"8865_CR53","doi-asserted-by":"publisher","first-page":"9003","DOI":"10.1523\/JNEUROSCI.0914-13.2013","volume":"33","author":"AB Rodgers","year":"2013","unstructured":"Rodgers, A. B., Morgan, C. P., Bronson, S. L., Revello, S. & Bale, T. L. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J. Neurosci. 33, 9003\u20139012 (2013).","journal-title":"J. Neurosci."},{"key":"8865_CR54","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nn.3695","volume":"17","author":"K Gapp","year":"2014","unstructured":"Gapp, K. et al. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat. Neurosci. 17, 667\u2013669 (2014).","journal-title":"Nat. Neurosci."},{"key":"8865_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.82","volume":"7","author":"AK Short","year":"2017","unstructured":"Short, A. K. et al. Exercise alters mouse sperm small noncoding RNAs and induces a transgenerational modification of male offspring conditioned fear and anxiety. Transl. Psychiatry 7, e1114-e (2017).","journal-title":"Transl. Psychiatry"},{"key":"8865_CR56","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2409790121","volume":"121","author":"N Trigg","year":"2024","unstructured":"Trigg, N. et al. Subchronic elevation in ambient temperature drives alterations to the sperm epigenome and accelerates early embryonic development in mice. Proc. Natl. Acad. Sci. USA 121, e2409790121 (2024).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8865_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2023.107769","volume":"172","author":"J Liu","year":"2023","unstructured":"Liu, J. et al. Paternal phthalate exposure-elicited offspring metabolic disorders are associated with altered sperm small RNAs in mice. Environ. Int. 172, 107769 (2023).","journal-title":"Environ. Int."},{"key":"8865_CR58","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s13578-023-01121-4","volume":"13","author":"Y Xue","year":"2023","unstructured":"Xue, Y. et al. Sex differences in paternal arsenic-induced intergenerational metabolic effects are mediated by estrogen. Cell Biosci. 13, 165 (2023).","journal-title":"Cell Biosci."},{"key":"8865_CR59","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1073\/pnas.1110368109","volume":"109","author":"W-M Liu","year":"2012","unstructured":"Liu, W.-M. et al. Sperm-borne microRNA-34c is required for the first cleavage division in mouse. Proc. Natl. Acad. Sci. USA 109, 490\u2013494 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8865_CR60","first-page":"635","volume":"143","author":"S Yuan","year":"2015","unstructured":"Yuan, S. et al. Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development. Development 143, 635\u2013647 (2015).","journal-title":"Development"},{"key":"8865_CR61","doi-asserted-by":"publisher","first-page":"67394","DOI":"10.18632\/oncotarget.18672","volume":"8","author":"L Guo","year":"2017","unstructured":"Guo, L. et al. Sperm-carried RNAs play critical roles in mouse embryonic development. Oncotarget 8, 67394\u201367405 (2017).","journal-title":"Oncotarget"},{"key":"8865_CR62","doi-asserted-by":"crossref","unstructured":"Trigg, N. A. et al. Subchronic elevation in ambient temperature drives alterations to the sperm epigenome and accelerates early embryonic development in mice. In Proceedings of the National Academy of Sciences of the United States of America. 121, e2409790121 (2024).","DOI":"10.1073\/pnas.2409790121"},{"key":"8865_CR63","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1001\/archpediatrics.2010.163","volume":"164","author":"SJ Frisbee","year":"2010","unstructured":"Frisbee, S. J. et al. Perfluorooctanoic acid, perfluorooctanesulfonate, and serum lipids in children and adolescents: results from the C8 Health Project. Arch. Pediatr. Adolesc. Med. 164, 860\u2013869 (2010).","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"8865_CR64","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1289\/ehp.1307893","volume":"122","author":"PI Johnson","year":"2014","unstructured":"Johnson, P. I. et al. The Navigation Guide - evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth. Environ. Health Perspect. 122, 1028\u20131039 (2014).","journal-title":"Environ. Health Perspect."},{"key":"8865_CR65","unstructured":"Biggers, J. D., Whitten, W. K., Whittingham, D. G. The culture of mouse embryos in vitro. in Methods in Mammalian Embryology 86\u2013116 (Freeman, 1971)."},{"key":"8865_CR66","unstructured":"Defence, Do. PFAS Investigation & Management Program, RAAF Base Williamtown: Australian Government Defence. Available from https:\/\/defence.gov.au\/Environment\/PFAS\/williamtown\/publications.asp (2022)."},{"key":"8865_CR67","unstructured":"CDC. National Health and Nutrition Examination Survey (NHANES): Centre for Diseases Control and Prevention. Available from https:\/\/www.cdc.gov\/nchs\/nhanes\/ (2023)."},{"key":"8865_CR68","doi-asserted-by":"publisher","first-page":"532","DOI":"10.30802\/AALAS-JAALAS-18-000129","volume":"58","author":"AS Mallien","year":"2019","unstructured":"Mallien, A. S. et al. Effects of soy in laboratory rodent diets on the basal, affective, and cognitive behavior of C57BL\/6 Mice. J. Am. Assoc. Lab Anim. Sci. 58, 532\u2013541 (2019).","journal-title":"J. Am. Assoc. Lab Anim. Sci."},{"key":"8865_CR69","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.clinms.2018.12.003","volume":"11","author":"R Desai","year":"2019","unstructured":"Desai, R., Harwood, D. T. & Handelsman, D. J. Simultaneous measurement of 18 steroids in human and mouse serum by liquid chromatography-mass spectrometry without derivatization to profile the classical and alternate pathways of androgen synthesis and metabolism. Clin. Mass Spectrom. 11, 42\u201351 (2019).","journal-title":"Clin. Mass Spectrom."},{"key":"8865_CR70","unstructured":"Hans J. Hedrich G. R. B., P. Petrusz. The Laboratory Mouse. 2nd (ed. Gillian R. Bullock P. P.) (Academic Press Inc., 2012)."},{"key":"8865_CR71","unstructured":"Institute of Medicine. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. 638 (The National Academies Press 2005)."},{"key":"8865_CR72","unstructured":"Australian Bureau of Statistics. National Health Survey: first results, body mass index, waist circumference, height and weight - Australia. Available from https:\/\/www.abs.gov.au\/statistics\/health\/health-conditions-and-risks\/national-health-survey\/latest-release (2022)."},{"key":"8865_CR73","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.freeradbiomed.2013.05.021","volume":"65","author":"TB Smith","year":"2013","unstructured":"Smith, T. B., Baker, M. A., Connaughton, H. S., Habenicht, U. & Aitken, R. J. Functional deletion of Txndc2 and Txndc3 increases the susceptibility of spermatozoa to age-related oxidative stress. Free Radic. Biol. Med. 65, 872\u2013881 (2013).","journal-title":"Free Radic. Biol. Med."},{"key":"8865_CR74","doi-asserted-by":"publisher","first-page":"3645","DOI":"10.1242\/jcs.01214","volume":"117","author":"KL Asquith","year":"2004","unstructured":"Asquith, K. L., Baleato, R. M., McLaughlin, E. A., Nixon, B. & Aitken, R. J. Tyrosine phosphorylation activates surface chaperones facilitating sperm-zona recognition. J. Cell Sci. 117, 3645\u20133657 (2004).","journal-title":"J. Cell Sci."},{"key":"8865_CR75","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/978-1-62703-038-0_14","volume":"927","author":"DP Evenson","year":"2013","unstructured":"Evenson, D. P. Sperm chromatin structure assay (SCSA\u00ae). Methods Mol. Biol. 927, 147\u2013164 (2013).","journal-title":"Methods Mol. Biol."},{"key":"8865_CR76","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1093\/biolre\/ioz008","volume":"100","author":"JH Martin","year":"2019","unstructured":"Martin, J. H. et al. Investigation into the presence and functional significance of proinsulin C-peptide in the female germline\u2020. Biol. Reprod. 100, 1275\u20131289 (2019).","journal-title":"Biol. Reprod."},{"key":"8865_CR77","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.ydbio.2016.06.035","volume":"417","author":"JH Martin","year":"2016","unstructured":"Martin, J. H., Nixon, B., Lord, T., Bromfield, E. G. & Aitken, R. J. Identification of a key role for permeability glycoprotein in enhancing the cellular defense mechanisms of fertilized oocytes. Dev. Biol. 417, 63\u201376 (2016).","journal-title":"Dev. Biol."},{"key":"8865_CR78","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1016\/j.dib.2016.07.046","volume":"8","author":"JH Martin","year":"2016","unstructured":"Martin, J. H., Bromfield, E. G., Aitken, R. J., Lord, T. & Nixon, B. Data on the concentrations of etoposide, PSC833, BAPTA-AM, and cycloheximide that do not compromise the vitality of mature mouse oocytes, parthenogencially activated and fertilized embryos. Data Brief. 8, 1215\u20131220 (2016).","journal-title":"Data Brief."},{"key":"8865_CR79","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1093\/biolre\/ioy009","volume":"98","author":"BJ Houston","year":"2018","unstructured":"Houston, B. J. et al. Heat exposure induces oxidative stress and DNA damage in the male germ line. Biol. Reprod. 98, 593\u2013606 (2018).","journal-title":"Biol. Reprod."},{"key":"8865_CR80","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1095\/biolreprod.114.122820","volume":"92","author":"T Lord","year":"2015","unstructured":"Lord, T., Martin, J. H. & Aitken, R. J. Accumulation of electrophilic aldehydes during postovulatory aging of mouse oocytes causes reduced fertility, oxidative stress, and apoptosis. Biol. Reprod. 92, 33 (2015).","journal-title":"Biol. Reprod."},{"key":"8865_CR81","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27892-2","volume":"8","author":"JH Martin","year":"2018","unstructured":"Martin, J. H., Bromfield, E. G., Aitken, R. J., Lord, T. & Nixon, B. Double strand break DNA repair occurs via non-homologous end-joining in mouse MII oocytes. Sci. Rep. 8, 9685 (2018).","journal-title":"Sci. Rep."},{"key":"8865_CR82","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1126\/science.aad6780","volume":"351","author":"U Sharma","year":"2016","unstructured":"Sharma, U. et al. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science 351, 391\u2013396 (2016).","journal-title":"Science"},{"key":"8865_CR83","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-020-6714-x","volume":"21","author":"O Yukselen","year":"2020","unstructured":"Yukselen, O., Turkyilmaz, O., Ozturk, A. R., Garber, M. & Kucukural, A. DolphinNext: a distributed data processing platform for high throughput genomics. BMC Genom. 21, 310 (2020).","journal-title":"BMC Genom."},{"key":"8865_CR84","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08865-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08865-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08865-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:04:03Z","timestamp":1761645843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08865-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":84,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8865"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08865-4","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,28]]},"assertion":[{"value":"10 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1487"}}