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Updated: Jun 30, 2025
A Rat Model of Mild Intrauterine Hypoperfusion with Microcoil Stenosis
Published on: January 7, 2018
Early postnatal moderate catch‑up growth in rats with nutritional intrauterine growth restriction preserves pulmonary
Lixia Ye1, Yajie Huang1, Kewei Chen1
1Department of Neonatology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, P.R. China.
Insights
Moderate postnatal catch-up growth following intrauterine growth restriction (IUGR) improves cognitive function and cardiovascular health. Rapid catch-up growth in IUGR rats led to pulmonary vascular dysfunction, while delayed growth caused brain deficits.
Area of Science:
- Developmental Biology
- Cardiovascular Physiology
- Neuroscience
Background:
- Intrauterine growth restriction (IUGR) impacts long-term health, with different postnatal growth patterns leading to distinct outcomes.
- Rapid catch-up growth is linked to adult pulmonary vascular dysfunction, while delayed growth causes cognitive deficits.
Purpose of the Study:
- To investigate the effects of moderate, rapid, and delayed postnatal catch-up growth on cognitive function and pulmonary vascular health in an IUGR rat model.
- To determine if moderate catch-up growth can mitigate adverse outcomes associated with IUGR.
Main Methods:
- An IUGR rat model was created via maternal nutritional restriction.
- Postnatal growth trajectories were manipulated by adjusting litter size.
- Cognitive function was assessed using the Y-maze test.
- Hemodynamic measurements evaluated mean pulmonary arterial pressure (mPAP).
- Pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (PVECs) were analyzed in vitro.
Main Results:
- Delayed growth in IUGR rats resulted in memory deficits linked to reduced hippocampal neural stem cell proliferation.
- Moderate catch-up growth improved memory function and maintained normal mPAP.
- Rapid catch-up growth in IUGR rats led to improved memory but elevated mPAP and pulmonary vascular remodeling.
- Excessive PASMC proliferation, migration, and anti-apoptotic activity, along with increased PVEC proliferation, were observed in the rapid catch-up group.
Conclusions:
- Moderate catch-up growth represents an optimal strategy for achieving better cognitive and cardiovascular health in adulthood after IUGR.
- Rapid catch-up growth exacerbates pulmonary vascular dysfunction, whereas delayed growth impairs cognitive function.
Abstract:
Intrauterine growth restriction (IUGR) with rapid postnatal catch-up growth is strongly associated with pulmonary vascular dysfunction in adulthood, whereas IUGR with delayed growth in early postnatal life results in long-term brain deficits. In the present study, it was hypothesized that IUGR with early moderate catch-up growth may alleviate pulmonary vascular remodeling in adulthood without affecting memory function. An IUGR model was established by restricting maternal nutrition during pregnancy. Different growth patterns were achieved by adjusting the litter size in each group during lactation. Rats meeting the weight requirement at weaning were selected for subsequent studies at three time points (3, 9 and 13 weeks). Cognitive function was evaluated using a Y-maze. Invasive hemodynamic measurements were conducted to measure the mean pulmonary arterial pressure (mPAP). In addition, primary pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (PVECs) were cultured to investigate their role in the increase in mPAP following rapid catch-up growth. The results showed that memory function deficits in the rats in the delayed growth group were associated with reduced proliferation of neural stem cells in the subgranular zone of the hippocampus. Furthermore, moderate catch-up growth at the three time points improved memory function while maintaining a normal mPAP. In adult IUGR rats experiencing rapid catch-up growth, although memory function improved, elevated mPAP and medial thickening of pulmonary arterioles were observed. Additionally, PASMCs exhibited excessive proliferation, migration and anti-apoptotic activity in the rapid catch-up group, and PVECs also displayed excessive proliferation. These results suggested that moderate catch-up growth after IUGR is a better strategy for optimal cognition and cardiovascular health in adulthood compared with rapid catch-up growth or delayed growth.
