Abstract
Elective caesarean delivery (CD) is an atypical early-life stressful event towards infants. It can pose a long-term effect to children's development by programming hypothalamus-pituitary-adrenal axis. However, the effect of elective CD on offspring's long-term cognitive function and the potential molecular mechanism remains unknown. In this study, by establishing CD mice model, we found that mice born with CD had lower corticosterone level at birth compared with those born by vaginal delivery (VD). Impairment in learning and memory was observed in CD offspring in adolescence, while the effect did not persist in the adulthood. In hippocampus, the expression of glucocorticoid receptor gene (Nr3c1) and FK506 binding protein gene 5 (Fkbp5) was higher in CD offspring in all postnatal time points. In hippocampus, the average methylation level at nerve growth factor-inducible protein A (NGFI-A) binding sites in exon 17 of Nr3c1, and the methylation in intron 1, intron 5 of Fkbp5 were all lower in CD offspring at infancy. Our data implicated that elective CD will cause delayed but non-permanent cognitive impairment in offspring. Insufficient glucocorticoid function caused by elective CD may bridge the association between this operative delivery mode and offspring's cognitive impairment. Methylation alterations in key regions of glucocorticoid signaling genes may partially explain the function of glucocorticoid related with elective CD.