Abstract
The present study aimed to investigate abnormal fetal cardiac pathological injury with exposure to a hypoxic environment during pregnancy. Pregnant hypoxia sheep models were prepared using artificial cabins. Sixteen pregnant sheep were randomly divided into three groups: normal group (NG), mild hypoxia group (MHG), and severe hypoxia group (SHG). The degree of SpO2, SaO2, breathing and heart rate, CO, and MDA were determined. HE staining, SEM, and TEM were used to evaluate the pathological changes of fetal myocardium. iTRAQ-based quantitative proteomics was employed to identify differentially expressed proteins. At day 30 and 90, the levels of SpO2 and SaO2 in SHG and MHG sheep met the diagnostic criteria. Ninety days after modeling, a dramatic reduction of breathing rate and increase of heart rate was observed in MHG and SHG comparing with that in NG (P < 0.05). At day 120, CO and MDA increased significantly in SHG and MHG than those in NG (P < 0.05), also in SHG compared with that in MHG (P < 0.05). HE staining and electron microscopy scanning showed that the myocardium in SHG and MHG had different levels of tissue edema and abnormal distribution of mitochondrion compared to NG. Eighty differentially expressed proteins were identified in fetal cardiac tissues. In conclusion, different degrees of pregnant hypoxia sheep models were successfully established. Prenatal hypoxia can cause serious damage to heart development of fetal sheep, as well as lead to the significant changes of hypoxia-associated proteins expression, which may be used to the further investigation for clinical applications.