Maternal antioxidant treatment prevents behavioural and neurological changes in offspring exposed to prenatal social stress [RNA-seq]

Maternal exposure to social stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. How the effects of maternal social stress are transmitted to the developing foetus is unclear. Using a rat model of maternal social stress during pregnancy, we explored the mechanisms by which maternal stress is conveyed to the foetus and the potential for targeted treatment to prevent disease in the offspring. Maternal stress induced oxidative stress in the placenta, but not in the foetal brain, which was prevented by a single administration of nanoparticle-bound antioxidant prior to the stress exposure. Moreover, this antioxidant treatment prevented prenatal stress-induced anxiety-like behaviour in juvenile male offspring, along with neurological and gene expression changes in the offspring brain. In vitro, placental conditioned medium or foetal plasma from stressed pregnancies caused changes to cultured cortical neurons, similar to those observed in the brains of juvenile offspring exposed to prenatal stress, and were found to contain altered levels of extracellular microRNAs but not corticosterone. The present study highlights the crucial role of the placenta, and molecules secreted from the placenta, in foetal brain development and provides evidence of the potential for treatment that can prevent maternal stress-induced foetal programming of neurological disease. Overall design: RNA sequencing was performed on RNA isolated form frontal cortices of gestational day 20 foetal rats. Dams had been exposed to chronic social stress during pregnancy, while control rats were left undisturbed. Stressed rats had been injected with nanoparticle-bound MitoQ (MitoQ-NP) or saline, while control rats had been injected with saline. For each of the 3 experimental conditions, samples were obtained from 4 independent foetuses (from different dams).