The maternal environment and behavior of sows differentially affect the neuro-epigenome of brain regions related to emotionality in their piglets

The environment to which females are exposed during pregnancy can modulate the neurodevelopment of her offspring, with epigenetic mechanism playing an important role in this process. In animals in captivity, stress due to confinement and living in a barren environment is among such maternal exposures that can affect the offspring's neurodevelopment, with the potential to compromise their behavior and welfare. Lack of stimulation in a confined environment prevent animals to express natural behaviors, resulting in the expression of stereotypies which are repetitive behaviors without an apparent function. Although stereotypies have been widely studied, little attention has been devoted to the postnatal effects of maternal stereotypy. Here we investigated how the maternal environment (barren or enriched) and stereotypic behavior (presence or absence) of sows affect the neuro-epigenome (methylation) of their piglets. We focused on brain regions related to emotionality, learning, memory, and stress response, namely the amygdala, frontal cortex, and hippocampus. Differentially methylated regions were investigated in these brain regions of male piglets born from sows kept in an enriched environment vs sows kept in the barren environment. Within the latter group of piglets, we compared the brain methylomes of those born from sows expressing stereotypic behavior vs sows not expressing stereotypic behavior. Our combined results emerging from significant differentially methylated regions emerging in each comparison show that while the epigenome of the hippocampus and frontal cortex of piglets is mainly affected by maternal environment, the epigenome of the amygdala is mainly affected by maternal stereotypic behavior. Additionally, we show that the molecular pathways and mechanisms triggered in the brains of piglets by maternal environment and stereotypic behavior are also different. In relation to gene function, introns are more prominently affected by maternal stereotypic behavior than environment. Although the epigenetic consequences of maternal stress in the offspring has been investigated to a large extent, the present study is the first to investigate the neuro- epigenomic effects of maternal enrichment and stereotypic behavior in mammals.