What about paternal obesity? Or what is not linked to autism?
"Obesity before pregnancy, not just during, may shape a child’s brain and raise the risk of autism spectrum disorder, a new study has found. Epigenetic changes in eggs triggered gene shifts linked to autism-like behaviors, revealing a critical window for prevention. ..."
"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). ..."
From the abstract:
"Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with early-life origins. Maternal obesity has been associated with increased ASD risk, yet the mechanisms and timing of susceptibility remain unclear.
Using a mouse model combining in vitro fertilization (IVF) and embryo transfer, we separated the effects of pre-conception and gestational obesity.
We found that maternal high fat diet (HFD) exposure prior to conception alone was sufficient to induce ASD-like behaviors in male offspring—including altered vocalizations, reduced sociability, and increased repetitive grooming—without anxiety-related changes.
These phenotypes were absent in female offspring and those exposed only during gestation.
Cortical transcriptome analysis revealed dysregulation and isoform shifts in genes implicated in ASD, including Homer1 and Zswim6.
Whole-genome bisulfite sequencing of hippocampal tissue showed hypomethylation of an alternative Homer1 promoter, correlating with increased expression of the short isoform Homer1a, which is known to disrupt synaptic scaffolding.
This pattern was specific to mice with ASD-like behaviors.
Our findings show that pre-conceptional maternal obesity can lead to lasting, isoform-specific transcriptomic and epigenetic changes in the offspring’s brain. These results underscore the importance of maternal health before pregnancy as a critical and modifiable factor in ASD risk."
"... Female offspring across all experimental groups showed no differences in measures of vocalization or social interaction, which are primary ASD-relevant behaviors (Figure S2). Given this result, and to remain within the scope and statistical design of our study, we focused subsequent transcriptomic and epigenomic analyses exclusively on male offspring. ..."
JABSOM Researchers Discover Link Between Maternal Obesity and Autism-like Behaviors in Offspring (original news release)
Graphical abstract
Figure 1. Experimental design.
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