Maternal obesity linked to autism-like behaviours in offspring

In a study conducted at the University of Hawaiʻi at Mānoa, researchers from the John A. Burns School of Medicine (JABSOM) have uncovered a mechanistic link between maternal obesity prior to pregnancy and autism-related behavioral outcomes in offspring.

The study, led by Professors Dr. Alika K. Maunakea and Dr. Monika Ward from the Department of Anatomy, Biochemistry & Physiology and the Yanagimachi Institute for Biogenesis Research (YIBR), sheds new light on how maternal health, even before conception, can program long-term neurodevelopmental trajectories in children. The work is published in the journal Cells.

The researchers demonstrated that obesity-induced changes in the mother's metabolic environment lead to lasting epigenetic alterations in oocytes—the precursors to eggs. These modifications, specifically changes in DNA methylation patterns, were carried into the developing embryos, ultimately disrupting the expression of critical neurodevelopmental genes such as Homer1. In male offspring, the study found increased expression of the short Homer1a isoform, known to interfere with synaptic function, resulting in behaviors consistent with 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 Dr. 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."

Utilizing an in vitro fertilization (IVF) and embryo transfer model, the team separated the effects of maternal obesity before conception from influences during pregnancy, enabling a more precise view of how early epigenetic programming unfolds. Behavioral tests in adolescent male mice revealed impaired social behaviors and repetitive grooming patterns reminiscent of ASD, correlating with altered gene regulation in the cortex and hippocampus.

"This discovery exemplifies the core mission of the YIBR," said Dr. 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."

The Yanagimachi Institute for Biogenesis Research, named after fertility pioneer Dr. Ryuzo Yanagimachi, fosters interdisciplinary collaboration in reproductive and developmental biology. This study, reflecting the synergy between Dr. Ward's expertise in reproductive science and Dr. Maunakea's research in neuroepigenetics, exemplifies the institute's commitment to translational discoveries with long-term health implications.

With rising global rates of both obesity and ASD, these findings could open new paths for early interventions—potentially even before conception. The researchers hope future studies will explore therapeutic strategies that may reverse or mitigate these effects through nutritional or pharmacological means.