Submitted on April 27, 2008
Revised on March 16, 2009
Accepted on March 16, 2009
Hypoxia during pregnancy in rats leads to early morphologic changes of atherosclerosis in adult offspring
Zhenhua Wang1, Ziyang Huang1*, Guorong Lu1, Ling Lin1, and Markus Ferrari2
1 Second Affiliated Hospital of Fujian Medical University
2 University of Jena
* To whom correspondence should be addressed. E-mail: huagzy{at}gmail.com.
Exposure to an adverse intrauterine environment increases the risk of cardiovascular disease later in adult life. However, the time-course relationship between prenatal hypoxia and the onset of atherosclerosis in offspring remains unknown. The purpose of this study is to evaluate the role of reduced fetal oxygen supply on early development of atherogenesis in the adult offspring and further assess its susceptibility to gender-, hyperlipidemia-, and postnatal hypoxemia -related differences. Based on a 4x2 full factorial design consisting of four factors of maternal hypoxia, gender, hyperlipidemia and postnatal hypoxemia, characteristics of growth were determined, and histopathological observation and morphometric analysis of the thoracic aortas were performed in Sprague-Dawley rats offspring. Intrauterine growth restriction, altered body shape at birth and accelerated postnatal weight gain occurred in the maternal hypoxia group, but did not occur in the control group. In 16-mo maternal hypoxia offspring, the thoracic aortas exhibited lesions similar to early events in atherosclerosis that involved impaired endothelial cells, thickening and fibration of intimas, infiltration of inflammatory cells to the subendothelial space, migration and proliferation of vascular smooth muscle cells to the intima. In contrast, no detectable pathological changes were observed in the offspring without maternal hypoxia exposure. Morphometric analysis further demonstrated that prenatal hypoxia caused a significant thickening of intima (P <0.001) with a main effect of 5.5 µm, approximately 2 fold increase compared to controls. In addition, there was a positive additive relationship between prenatal hypoxia and hyperlipidemia on the intimal thickness (P <0.05). There were no other main effects or interaction among these four factors. In summary, our results indicate that maternal hypoxia during pregnancy leads to early pathological appearances of atherogenesis in adult offspring. This effect was enhanced with hyperlipemia, but was unaffected by postnatal hypoxia or gender.
