Early moderate catch-up growth after birth helps IUGR rats achieve good pulmonary vascular and cognitive function in adulthood

Background: and aims: Intrauterine growth restriction (IUGR) with postnatal catch-up growth is strongly associated with pulmonary vascular dysfunction in adulthood, and postnatal nutrient restriction leads to long-term brain deficits. In this study, we hypothesize that early moderate catch-up growth can alleviate pulmonary vascular remodeling without affecting their memory function. Additionally, we investigated whether pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (PVECs) were involved in pulmonary hypertension caused by rapid catch-up growth. Methods: and results: We established an IUGR model by limiting maternal nutrition during pregnancy, and created different growth patterns by adjusting the number of offspring in each group during lactation. Three different time points from infancy to adulthood (3w, 9w, and 13w) were chosen for subsequent studies. The Y-maze was used to evaluate the rats’ cognitive function. The results showed that deficits in memory function due to delayed growth were associated with reduced proliferation of neural stem cells in the subgranular zone (SGZ) of the hippocampus. Furthermore, moderate catch-up growth improved memory function without affecting mPAP, while rapid catch-up growth increased susceptibility to cardiovascular diseases in adulthood. Higher mPAP, thickened pulmonary artery media, narrowed vessel lumen, and increased pulmonary small vessel muscularization confirmed this. PASMCs in the adult rats that underwent rapid catch-up growth exhibited excessive proliferation, migration, and anti-apoptotic activity, while PVECs also exhibited excessive proliferation. Conclusion: The results suggest that moderate catch-up growth after IUGR is better for optimal cognition and cardiovascular health in adulthood than rapid catch-up growth or delayed growth.