Intrauterine Growth Restriction Impairs Hippocampal Neurogenesis and Cognition via Tet1/Notch signaling in Offspring

Intrauterine growth restriction (IUGR) increases the risk of cognitive impairments in offspring in later life. However, the precise mechanisms underlying this process remain elusive. Here, we used two IUGR mouse models and observed learning and memory deficits in adult IUGR offspring. IUGR induces decreased hippocampal neurogenesis from the early postnatal period to adulthood by reducing the proliferation of neural stem cells (NSCs). Mechanistically, persistently decreased Tet1 in hippocampal NSCs induces the inhibition of Notch signaling. Overexpression of Tet1 activates Notch signaling, offsets the decline in neurogenesis, and enhances learning and memory abilities in IUGR offspring, which provides potential new targets for improving the long-term cognitive outcomes of IUGR.