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

Journal article

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

Authors: McKnight, EGW; Lee, G; Chong, C; Foster, JA; Zhang, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Brain and Behavior
• Volume: 16
• Issue: 2
• Article number: e71195
• Publication date: 2026-01-28
• Acceptance date: 2025-12-26
• DOI: 10.1002/brb3.71195
• EISSN: 2162-3279
• ISSN: 2162-3279
• Language: English
• Keywords: paternal diet; MRI; neurodevelopment; high‐fat/high‐simple sugar