The Effects Of Maternal Hypoxia On The Heart Development In Fetal And Neonatal Rats

Fetal hypoxia leads to progressive cardiac remodeling in the rat offspring. Our objective is to determine the effects of hypoxia on heart remodeling in fetus and neonates. Pregnant rats were treated with normoxia or hypoxia (10.5% O2) from day 15 to 21 of gestation. Hearts were isolated from 21‐day fetuses (E21) and 7‐day‐old pups (PD7). The fibrillar collagen was examined by scanning electron microscopy (SEM). The expression of matrix metalloproteinases (MMP) 1, 2, 9 & 13, tissue inhibitors of metalloproteinases (TIMP) 1, 2, 3 and collagen 1 & 3 in the heart was measured by Western blots. Maternal hypoxia caused a significant decrease in the body weight of the pups at both E21 and PD7. The heart weight was decreased at PD7, but not in E21. SEM indicated less amount of fibrillar collagen at E21 but greater amount of collagen at PD7 in the heart of hypoxic pups, as compared with those of control animals. Myocardium wall thickness was decreased by hypoxia in both E21 and PD7. Hypoxia also reduced collagen‐1 and MMP‐1 in fetuses, while increased collagen‐1 and MMP‐1 in neonates. MMP‐13 was enhanced in fetuses but reduced in neonates, while TIMP‐3 level was increased in both developmental stages. There was no change in MMP‐2 & 9, TIMP‐1 & 2 and collagen‐3. Maternal hypoxia results in differential remodeling of fibrillar collagen in fetal and neonatal hearts, which may be mediated by the altered expression patterns of MMPs and TIMPs.