DOI: 10.1098/rspb.2026.0535 ISSN: 1471-2954

Paternal dietary macronutrients affect the seminal vesicle fluid proteome and fetal development: a geometric framework for nutrition study in mice

Erin L. Macartney, Alistair M. Senior, Lewin Small, Angela J. Crean, Taylor Pini, Tamara J. Pulpitel, Marcelo A. Nobrega, Romain Barrès, Stephen J. Simpson

Abstract

Seminal plasma can have wide-ranging effects on reproductive fitness—from affecting sperm fertilization capacity and female reproductive physiology to influencing offspring viability and health. Seminal plasma can also change in response to environmental conditions including diet, which of itself is known to affect reproductive traits and fitness outcomes. However, an understanding of how paternal diet alters seminal plasma composition and how these effects relate to fetal development remains elusive. Here, we applied the geometric framework for nutrition to systematically manipulate dietary macronutrient balance in male mice and determine dietary effects on the seminal vesicle fluid (SVF; comprising much of the seminal plasma) proteome, as well as relate differences in the proteome to aspects of fetal development. We (i) identified the largest number of proteins in the mouse SVF proteome to date, (ii) determined a set of proteins that were significantly affected by dietary macronutrients, (iii) showed that differences in a protein related to lipid mobilization and metabolism (APOA4) were correlated with fetal development, and (iv) detected dietary effects on aspects of fetal development that were unrelated to SVF protein abundance. This study provides a comprehensive characterization of the male SVF proteome across nutritional space and highlights potential functional ways in which male diet and the seminal plasma may mediate fitness.

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