Fetal Growth Restriction Impairs Hippocampal Neurogenesis and Cognition via Tet1 in Offspring

However, the precise mechanisms remain elusive. Using dexamethasone-induced FGR and protein restriction-influenced FGR mouse models, we observed learning and memory deficits in adult FGR offspring.

FGR induces decreased hippocampal neurogenesis from the early postnatal period to adulthood by reducing the proliferation of neural stem cells (NSCs). We further found a persistent decrease of Tet1 expression in hippocampal NSCs of FGR mice. Mechanistically, Tet1 downregulation results in hypermethylation of the Dll3 and Notch1 promoters and inhibition of Notch signaling, leading to reduced NSC proliferation.