Maternal obesity before pregnancy linked to autism-like behaviours in offspring, University of Hawai‘i mice study finds
Key Takeaways:
- University of Hawai‘i researchers have shown that maternal obesity prior to conception can cause epigenetic changes in eggs that affect offspring brain development.
- Male offspring of obese mothers displayed autism-like traits, including altered social behaviour and increased repetitive actions, linked to changes in the Homer1 gene.
- The findings, obtained using an in vitro fertilisation model, may inform early interventions aimed at reducing neurodevelopmental risk before pregnancy.
Maternal health before conception found to have long-term impact on brain development
A study conducted at the University of Hawai‘i at Mānoa’s John A. Burns School of Medicine (JABSOM) has revealed a direct link between a mother’s weight before pregnancy and autism-like behaviours in her offspring.
Published in the journal Cell, the research offers new insight into how maternal health in the period before conception can influence a child’s brain development. The team, led by Professors Alika K. Maunakea and Monika Ward from JABSOM’s Department of Anatomy, Biochemistry & Physiology and the Yanagimachi Institute for Biogenesis Research (YIBR), found that maternal obesity can trigger metabolic changes which cause lasting epigenetic modifications in eggs.
These modifications are transmitted to the developing embryo, altering the expression of genes involved in brain development, including Homer1, a protein that regulates synaptic signalling, learning, memory, and responses to neural activity.
Gene changes linked to autism-like behaviours in male offspring
The researchers discovered that male offspring of obese mothers exhibited increased levels of a specific Homer1 gene isoform. This variant is known to disrupt neural connections and has been associated with behaviours linked to autism spectrum disorder (ASD).
“This work highlights how a mother’s health prior to pregnancy, not just during gestation, can shape her child’s brain development in profound ways,” said Professor Maunakea. “We were surprised to find that even without direct maternal contact after conception, these epigenetic imprints from the egg carried enough weight to alter behaviour.”
IVF and embryo transfer model used to isolate effects
To separate the effects of obesity before pregnancy from those during gestation, the team used an in vitro fertilisation (IVF) and embryo transfer model. This allowed them to examine the influence of early epigenetic programming without confounding maternal factors during pregnancy.
When the adolescent male mice were tested, behavioural assessments showed reduced social interactions and increased repetitive behaviours — characteristics that parallel features of ASD. These changes were traced to altered regulation of brain-related genes.
“This discovery exemplifies the core mission of the YIBR,” said Professor Ward. “By leveraging our institute’s expertise in developmental biology, reproductive science and epigenetics, we are beginning to understand how early-life programming can ripple through generations.”
Potential for early intervention before conception
Both obesity and ASD have been increasing worldwide, underscoring the public health importance of these findings. The researchers suggest that interventions — potentially nutritional or pharmacological — could be developed to reverse or reduce the impact of pre-pregnancy obesity on brain development.
The study highlights the importance of maternal health not only during pregnancy but also in the months and years before conception, signalling that preventive measures could have lasting benefits for the next generation.
CCH Insight:
We have to interpret this study with caution, because it was conducted with mice, so we cannot extrapolate directly to humans. However, it serves as a reminder that obesity reduces fertility, and obesity during pregnancy carries risks to mother and baby, so pre-conception should be a priority for pro-active obesity care interventions.
