How do lifestyle and environmental factors influence the sperm epigenome? Effects on sperm fertilising ability, embryo development, and offspring health
Akhatova A. Jones C. Coward K. Yeste M.
December 2025BioMed Central Ltd
Clinical Epigenetics
2025#17Issue 1
Recent studies support the influence of paternal lifestyle and diet before conception on the health of the offspring via epigenetic inheritance through sperm DNA methylation, histone modification, and small non-coding RNA (sncRNA) expression and regulation. Smoking may induce DNA hypermethylation in genes related to anti-oxidation and insulin resistance. Paternal diet and obesity are associated with greater risks of metabolic dysfunction in offspring via epigenetic alterations in the sperm. Metabolic changes, such as high blood glucose levels and increased body weight, are commonly observed in the offspring of fathers subjected to chronic stress, in addition to an enhanced risk of depressive-like behaviour and increased sensitivity to stress in both the F0 and F1 generations. DNA methylation is correlated with alterations in sperm quality and the ability to fertilise oocytes, possibly via a differentially regulated MAKP81IP3 signalling pathway. Paternal exposure to toxic endocrine-disrupting chemicals (EDCs) is also linked to the transgenerational transmission of increased predisposition to disease, infertility, testicular disorders, obesity, and polycystic ovarian syndrome (PCOS) in females through epigenetic changes during gametogenesis. As the success of assisted reproductive technology (ART) is also affected by paternal diet, BMI, and alcohol consumption, its outcomes could be improved by modifying factors that are dependent on male lifestyle choices and environmental factors. This review discusses the importance of epigenetic signatures in sperm—including DNA methylation, histone retention, and sncRNA—for sperm functionality, early embryo development, and offspring health. We also discuss the mechanisms by which paternal lifestyle and environmental factors (obesity, smoking, EDCs, and stress) may impact the sperm epigenome.
Environmental factors , Epigenetics , Lifestyle , Offspring health , Sperm
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Nuffield Department of Women’s and Reproductive Health, Level 3, Women’s Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, United Kingdom
School of Medicine, Nazarbayev University, Zhanybek-Kerey Khan Street 5/1, Astana, 010000, Kazakhstan
Biotechnology of Animal and Human Reproduction (TechnoSperm), Institute of Food and Agricultural Technology, University of Girona, Girona, 17003, Spain
Unit of Cell Biology, Department of Biology, Faculty of Sciences, University of Girona, Girona, 17003, Spain
Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, 08010, Spain
Nuffield Department of Women’s and Reproductive Health
School of Medicine
Biotechnology of Animal and Human Reproduction (TechnoSperm)
Unit of Cell Biology
Catalan Institution for Research and Advanced Studies (ICREA)
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