# Probing the Influence of Paternal Diet on Offspring Neuroanatomy With Mouse MRI

**Authors:** Emma G. W. McKnight, Gail Lee, Cheryl Chong, Jane A. Foster, Tie‐yuan Zhang, Jason P. Lerch, Brian J. Nieman, Mark R. Palmert

PMC · DOI: 10.1002/brb3.71195 · Brain and Behavior · 2026-01-28

## TL;DR

This study investigates whether a father's high-fat diet affects his offspring's brain structure, finding no significant impact.

## Contribution

The study demonstrates that paternal diet alone does not alter offspring brain structure volumes in mice.

## Key findings

- Paternal HF/HSS diet caused significant weight gain in fathers but not in offspring.
- Offspring brain structure volumes were not significantly affected by paternal diet alone.
- Maternal diet appears necessary for observed brain structure changes in offspring.

## Abstract

Previous studies have established that parental consumption of a diet high in fat and simple sugar (HF/HSS) leads to long‐term effects on offspring brain development. However, most studies have focused on the effects of maternal diets or the combined effects of both parents’ diets. As literature suggests that fathers’ environmental factors can also impact offspring brain development, we aimed to explore the impact of isolated paternal consumption of an HF/HSS diet on offspring brain structure.

C57Bl/6J male mice were acclimated to an HF/HSS diet for eight weeks prior to mating with females who consumed standard chow (control diet, CD). A matching paternal control group was fed the CD during the acclimation period. Throughout gestation and lactation all dams and offspring were fed the CD; all pups were weaned at postnatal day 21 (P21) and stayed on the CD. At P42 offspring brains were prepared for ex vivo magnetic resonance imaging (MRI). Brain MR images were then segmented for volumetric structural analysis.

HF/HSS‐fed sires gained more weight during acclimation than CD sires (p < 0.001). However, offspring weights at weaning (P21) and at endpoint (P42) were not significantly affected by paternal diet. Offspring brain morphology, as assessed by volume measurements of 185 brain structures, was not significantly affected by sire HF/HSS diet alone.

While small structural changes cannot be ruled out, the results suggest that previously observed changes in offspring brain structure attributed to parental consumption of HF/HSS diet (selected to mimic some aspects of the human “Western Diet”) require maternal consumption.

This study aimed to determine if paternal consumption of a high‐fat/high‐simple‐sugar (HF/HSS) diet prior to conception recapitulates the offspring brain structure volume changes seen with parental preconception consumption of an HF/HSS diet. Using C57Bl6/J mice and MRI, we established that there were no significant effects of paternal HF/HSS eating habits on their offspring's brain structure volumes despite significant effects on paternal weight.

## Linked entities

- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** neuropsychiatric disorders (MESH:D001523), obese (MESH:D009765), schizophrenia (MESH:D012559), NDD (MESH:D002658), ASD (MESH:D000067877), ADHD (MESH:D001289), type 2 diabetes (MESH:D003924), cancers (MESH:D009369), cardiovascular diseases (MESH:D002318), overweight (MESH:D050177), diabetes (MESH:D003920), depression (MESH:D003866), kidney disease (MESH:D007674), anxiety (MESH:D001007), weight gain (MESH:D015430), inflammation (MESH:D007249), mammary and other solid tumors (MESH:D015674)
- **Chemicals:** sugar (MESH:D000073893), ProHance (MESH:C062402), heparin (MESH:D006493), fat (MESH:D005223), omega-3 fatty acids (MESH:D015525), HF (MESH:D006195), CD (-), simple sugar (MESH:D009005), sucrose (MESH:D013395), carbohydrates (MESH:D002241), sodium azide (MESH:D019810), PFA (MESH:C003043), water (MESH:D014867), isoflurane (MESH:D007530), alcohol (MESH:D000438)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), C57Bl/6J — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0192)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12848517/full.md

## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12848517/full.md

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Source: https://tomesphere.com/paper/PMC12848517