The University of Sheffield-led study, with key 3D placental structure analysis led by the University of Bristol, found that although dietary differences had no major effect on fertility, both high-fat "Western-style" diets and low-protein diets in male mouse models altered key biological processes in the placenta after fertilisation.
The study's findings add to growing evidence that paternal health and nutrition before conception may play an important role in early development. With pre-conception advice often focusing on women, these findings suggest men's health should also be part of the conversation.
As the placenta regulates the exchange of nutrients between mother and fetus, changes in its development could potentially influence later health. In addition to regulating maternal cardiovascular and metabolic health during pregnancy, poor placental development is associated with pregnancy complications such as preeclampsia.
The study focused on male mice that were fed different diets for eight weeks before mating. Some received a standard diet, while others were fed a low-protein diet or a high-fat, high-sugar "Western" diet designed to replicate poor quality diets commonly consumed by men worldwide.
Some diets were also supplemented with nutrients involved in epigenetic regulation, allowing the team to explore whether these pathways might influence the effects observed.
Although the diets did not markedly affect fertility, they were associated with important changes in the developing placenta once pregnancy was established. When the researchers examined placental tissue early in pregnancy, they observed alterations in placental metabolism and structure, particularly in the ectoplacental cone, a region important for early placenta formation.
Later in pregnancy, analysis of placental gene activity revealed changes in gene expression patterns linked to the father's diet.
One key finding was a change in sex-specific gene activity in the placenta. This matters because male and female placentas can respond differently to environmental conditions during pregnancy.
These findings suggest paternal diet can reshape the normal biological differences between male and female placentas.
Lead researcher, Dr Adam Watkins, from the University of Sheffield's School of Medicine and Population Health, said: "We've known for a long time that a mother's diet is the foundation of a healthy pregnancy, but our research suggests that fathers are far from being silent partners in this process.
"What a man eats in the period leading up to conception may do more than just affect his own health - it could play a key role in shaping the wellbeing of both his partner and the developing baby.
"While this study was conducted in mice, the fundamental biological blueprints for sperm production and placental function are remarkably similar to our own. While further research in humans is essential to map these specific mechanisms, these findings suggest paternal nutrition is a vital, and often overlooked, piece of the fertility puzzle."
Dr Augusto Coppi, Senior Lecturer in Veterinary Anatomy at the University of Bristol, who led the study's analysis of the placental structure, added: "Using Bristol-led gold-standard 3D quantitative analysis, known as design-based stereology, we were able to test whether the molecular changes were accompanied by measurable changes in placental structure.
"Interestingly, late in pregnancy we found these molecular shifts occurred without major changes in overall placental size or structure."
The study also found male mice consuming the Western-style diet produced a biologically meaningful metabolic effect, strengthening the rationale for the model, including:
- increased body fat
- elevated liver cholesterol and fatty acids
- changes in gut microbiota composition
The team now hopes to investigate whether similar mechanisms operate in humans, with the long-term aim of informing practical pre-conception guidance that recognises pregnancy preparation as a shared responsibility between both parents.
The research team would like to highlight as the study was conducted in mice, it should not be interpreted as direct clinical advice for individual couples.
Paper
'Paternal over- and under-nutrition program fetal and placental development in a sex-specific manner in mice' by Hannah L Morgan, Nader Eid, Antonio Augusto Coppi, Adam J Watkins et al. in eLife [open access]
