Summary: New research shows that maternal obesity before conception can set lasting epigenetic marks in egg cells that influence neurodevelopment and produce autism-related behaviors in offspring. Using an IVF and embryo transfer approach in mice to isolate pre-conception effects, scientists identified altered DNA methylation patterns that changed expression of genes such as Homer1.
In male offspring, these epigenetic changes corresponded with reduced social interaction and increased repetitive grooming—behaviors that mirror features of autism spectrum disorder (ASD). The work highlights the importance of maternal health before pregnancy and suggests the potential for interventions initiated prior to conception.
Key Facts
- Epigenetic connection: Maternal obesity prior to pregnancy altered DNA methylation in oocytes, leading to persistent changes in offspring neurodevelopmental gene expression.
- Autism-related behaviors: Male offspring displayed impaired social behavior and repetitive grooming associated with elevated expression of the short Homer1a isoform.
- Pre-conception effect isolated: An IVF and embryo transfer model confirmed these changes originate before pregnancy rather than during gestation.
Source: University of Hawaii
Overview of the study
Researchers at the University of Hawaiʻi at Mānoa, led by Dr. Alika K. Maunakea and Dr. Monika Ward from the John A. Burns School of Medicine, investigated how a mother’s metabolic state before conception can influence her offspring’s brain development. Their study demonstrates that obesity-related metabolic changes in females can create stable epigenetic alterations in oocytes. These changes are then transmitted to embryos, disrupting the regulation of genes important for synaptic function and neurodevelopment.
The team found that exposure to a high-fat diet before conception produced measurable changes in DNA methylation within oocytes. Those epigenetic marks persisted into embryonic development and altered transcriptional programs in the offspring’s brain. Among the affected genes, Homer1 stood out: an alternative promoter became hypomethylated in the hippocampus, coinciding with higher levels of the short Homer1a isoform, which is known to interfere with normal synaptic scaffolding.
Behavioral testing focused on adolescent mice and revealed sex-specific outcomes. Male offspring from mothers exposed to pre-conception obesity showed social deficits, altered vocalizations, and increased repetitive grooming—behaviors commonly used as mouse analogues for ASD features. Female offspring did not display these phenotypes, and offspring exposed only during gestation lacked the same behavioral changes, supporting the conclusion that the window of susceptibility included the pre-conception period.
To separate maternal pre-conception effects from gestational influences, researchers used IVF followed by embryo transfer into healthy surrogate mothers. This experimental design allowed the team to attribute behavioral and molecular differences to epigenetic programming that occurred before fertilization rather than to the intrauterine environment.
Cortical transcriptome analyses showed shifts in gene expression and isoform usage for several genes linked to ASD, including Homer1 and Zswim6. Whole-genome bisulfite sequencing of hippocampal tissue revealed specific hypomethylation at an alternative Homer1 promoter in mice that developed ASD-like behaviors, supporting a model in which pre-conception maternal metabolism produces targeted neuroepigenetic dysregulation.
Dr. Maunakea emphasized the study’s implication: maternal health before pregnancy can have a direct and lasting effect on a child’s neural wiring. Dr. Ward highlighted the interdisciplinary strength of their institute, which combines reproductive biology and epigenetics to address how early-life programming may affect future generations.
With both obesity and ASD on the rise worldwide, these findings point toward new preventive strategies that could begin before conception. The authors suggest future research should evaluate whether nutritional or pharmacological interventions prior to pregnancy can reverse or reduce these epigenetic changes and their behavioral outcomes.
The study has been accepted for publication in the journal Cells and represents a step forward in understanding how modifiable maternal factors can shape offspring brain development.
About this genetics, obesity, and autism research news
Author: Matthew Campbell
Source: University of Hawaii
Contact: Matthew Campbell – University of Hawaii
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Pre-Conception Maternal Obesity Confers Autism Spectrum Disorder-like Behaviors in Mice Offspring Through Neuroepigenetic Dysregulation” by Alika K. Maunakea et al. Cells. DOI: 10.3390/cells14151201
Abstract
Pre-Conception Maternal Obesity Confers Autism Spectrum Disorder-like Behaviors in Mice Offspring Through Neuroepigenetic Dysregulation
Autism spectrum disorder is a complex neurodevelopmental condition originating early in life. Although maternal obesity has been linked to elevated ASD risk, the timing and mechanisms of this vulnerability are not fully understood.
Using a mouse model that combines in vitro fertilization and embryo transfer, the investigators separated pre-conception effects from gestational influences. They found that maternal exposure to a high-fat diet before conception was sufficient to produce ASD-like behaviors in male offspring—such as altered vocalizations, reduced social interaction, and increased repetitive grooming—without accompanying anxiety-related changes.
These male-specific phenotypes were not present in female offspring or in offspring exposed to maternal obesity only during gestation. Transcriptomic profiling of the cortex revealed dysregulation and shifts in isoform usage for genes implicated in ASD, including Homer1 and Zswim6. Genome-wide bisulfite sequencing of hippocampal tissue identified hypomethylation at an alternative Homer1 promoter, correlating with increased expression of the short Homer1a isoform that can disrupt synaptic scaffolding.
Overall, these results indicate that pre-conception maternal obesity can cause durable, isoform-specific transcriptional and epigenetic changes in the offspring brain, highlighting maternal health before pregnancy as a critical, modifiable factor in ASD risk.