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Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice

Watkins, Adam J.; Dias, Irundika; Tsuro, Heather; Allen, Danielle; Emes, Richard D.; Moreton, Joanna; Wilson, Ray; Ingram, Richard J. M.; Sinclair, Kevin D.


Irundika Dias

Heather Tsuro

Danielle Allen

Richard D. Emes

Joanna Moreton

Ray Wilson

Richard J. M. Ingram

Professor of Developmental Biology


© 2018 National Academy of Sciences. All rights reserved. The association between poor paternal diet, perturbed embryonic development, and adult offspring ill health represents a new focus for the Developmental Origins of Health and Disease hypothesis. However, our understanding of the underlying mechanisms remains ill-defined. We have developed a mouse paternal low-protein diet (LPD) model to determine its impact on semen quality, maternal uterine physiology, and adult offspring health. We observed that sperm from LPD-fed male mice displayed global hypomethylation associated with reduced testicular expression of DNA methylation and folate-cycle regulators compared with normal protein diet (NPD) fed males. Furthermore, females mated with LPD males display blunted preimplantation uterine immunological, cell signaling, and vascular remodeling responses compared to controls. These data indicate paternal diet impacts on offspring health through both sperm genomic (epigenetic) and seminal plasma (maternal uterine environment) mechanisms. Extending our model, we defined spermand seminal plasma-specific effects on offspring health by combining artificial insemination with vasectomized male mating of dietarymanipulated males. All offspring derived from LPD sperm and/or seminal plasma became heavier with increased adiposity, glucose intolerance, perturbed hepatic gene expression symptomatic of nonalcoholic fatty liver disease, and altered gut bacterial profiles. These data provide insight into programming mechanisms linking poor paternal diet with semen quality and offspring health.


Watkins, A. J., Dias, I., Tsuro, H., Allen, D., Emes, R. D., Moreton, J., …Sinclair, K. D. (2018). Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice. Proceedings of the National Academy of Sciences, 115(40), 10064-10069.

Journal Article Type Article
Acceptance Date Jul 26, 2018
Online Publication Date Aug 27, 2018
Publication Date Oct 2, 2018
Deposit Date Oct 5, 2018
Publicly Available Date Oct 5, 2018
Journal Proceedings of the National Academy of Sciences
Print ISSN 0027-8424
Electronic ISSN 1091-6490
Publisher National Academy of Sciences
Peer Reviewed Peer Reviewed
Volume 115
Issue 40
Pages 10064-10069
Keywords developmental programming; maternal responses; metabolic disorder; paternal diet; semen quality
Public URL
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