Caesarean section and offspring's emotional development: Sex differences and the role of key neurotransmitters.

Increasing caesarean section (CS) rates are of global concern not only for health care providers but also from a more general public health point of view. Growing concern on the association between CS and offspring's neurodevelopmental outcomes have been raised in recent years, but the effect of CS on offspring's emotional development is rarely reported. By using mice models, we have set up two groups, ie. offspring born via CS and in-fostered by dams with vaginal delivery (VD), and offspring born via VD and in-fostered by their non-biological mothers. Depression-like behavioral was evaluated by sucrose preference test and forced swimming test, and anxiety-like behavioral was evaluated by open-field test and elevated plus maze test, respectively during offspring's adolescence and adulthood. Offspring's prefrontal cortex was collected for HE staining and assessment for DA, HVA, 5-HT, 5-HIAA. It was found that offspring born of CS have anxiety-like and depression-like behaviors in adolescence and adulthood. Male offspring was sensitive to be depressive and female offspring tended to be anxious. Although no significant sex difference was observed, there existed edema and nuclear retraction of neurons in the prefrontal cortex in offspring via CS during adolescence and adulthood. Compared with offspring born via VD, offspring through CS had shown higher DA and HVA levels while lower 5-HT and 5-HIAA levels in adolescence and adulthood, and this difference was observed in female offspring. The findings highlight the sex-specific effect of CS on offspring's emotional development. Variations in key neurotransmitters in the prefrontal cortex may partly explain the association between CS and offspring's emotional symptoms.