Researchers at the University of Hawaiʻi at Mānoa John A. Burns School of Medicine (JABSOM) have uncovered a connection between a mother's weight before pregnancy and autism-like behaviors in her offspring.
Published in Cell , the study marks a significant advance in understanding how early life factors influence brain development.
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), the research shows that maternal obesity triggers metabolic shifts that cause lasting epigenetic changes in a mother's eggs. These changes are passed on to the developing embryo and affect genes involved in brain development, including Homer1, a protein important for regulating synaptic signaling, learning, memory and response to neural activity.
In male offspring, researchers identified increased levels of a specific Homer1 gene isoform that is known to interfere with neural connections and is associated with behaviors 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 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 behavior."
Clearer understanding through IVF model
To isolate the effects of pre-pregnancy obesity from those during gestation, the researchers used an in vitro fertilization (IVF) and embryo transfer model. This approach allowed them to study early epigenetic programming more precisely.
Behavioral assessments of adolescent male mice revealed impaired social interactions and repetitive behaviors. These traits, which mirror characteristics of ASD, were linked to altered gene regulation in the brain.
"This discovery exemplifies the core mission of the YIBR," said 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."
With both obesity and ASD rates increasing worldwide, the findings may lead to early interventions, potentially even before conception. Future research may explore nutritional or pharmacological strategies to reverse or reduce these effects.
