Obesity before pregnancy led to autism-like behaviors in male offspring of mice. Digest
Obesity in mothers has been linked to autism risk in children, but it's still unclear whether that risk begins during pregnancy or even earlier.
Using a controlled assisted reproduction model, a new study separated the effects of obesity before conception from those during pregnancy. Female mice were fed either a high-fat diet (45 percent fat) that induced obesity or a normal-fat diet (10 percent fat) that maintained normal weight. Their eggs were collected, fertilized in the lab, and implanted into either lean or obese surrogate mothers. After birth, all pups were raised by lean foster mothers on a normal diet to ensure conditions were as similar as possible during nursing and early care.
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Autism-related behaviors and changes in brain gene activity appeared only in a subset of male offspring from obese egg donors carried by normal-weight mothers:
- These mice made more calls at postnatal day 8 and fewer by day 10. This pattern is reminiscent of delayed vocal development observed in autism.
- They showed reduced interest in social interaction and preferred to spend time alone when given a choice.
- Grooming behavior was altered in frequency but not duration, suggesting subtle shifts in repetitive behavior.
- The gene Homer1, which helps organize synaptic connections, showed altered activity in affected mice. Its short isoform, Homer1a, which can disrupt these connections and modify signaling, was elevated in those with autism-like traits.
Obesity before pregnancy, even without any exposure during gestation, may trigger long-lasting changes in the developing brain of the offspring. This may alter how brain circuits form, especially in males, and result in behaviors resembling autism. These lasting effects were linked to epigenetic changes, chemical modifications that influence when and how genes are active. Such changes may start in the mother's eggs before conception and later shape how genes function as the brain develops.
While the research was done in mice, it adds to growing evidence that maternal health before pregnancy can shape brain development in offspring. Larger studies are needed to explore whether similar patterns occur in humans and whether early interventions could reduce neurodevelopmental risk. Discover effective strategies to combat obesity in this clip featuring Dr. Layne Norton.