Restriction of placental function alters heart development in the sheep fetus. [Am J Physiol Regul Integr Comp Physiol] Journal article

Placental insufficiency, resulting in restriction of fetal substrate supply, is a major cause of intrauterine growth restriction (IUGR) and increased neonatal morbidity. Fetal adaptations to placental restriction maintain the growth of key organs including the heart, but the impact of these adaptations on individual cardiomyocytes is unknown. Placental and hence fetal growth restriction was induced in fetal sheep by removing the majority of caruncles in the ewe before mating (placental restriction, PR). Vascular surgery was performed on 13 Control and 11 PR fetuses at 110-125d gestation (term=150+/-3d). PR fetuses with a mean gestational PO2<17mmHg were defined as hypoxic. At post mortem (<135 or >135d), fetal hearts were collected, and cardiomyocytes isolated and fixed. Proliferating cardiomyocytes were counted by immunohistochemistry of Ki67 protein. Cardiomyocytes were stained with methylene blue to visualise the nuclei and the proportion of mononucleated cells, length and width of cardiomyocytes were measured. PR resulted in chronic fetal hypoxia, IUGR and elevated plasma cortisol concentrations. Although there was no difference in relative heart weights between Control and PR fetuses, there was an increase in the proportion of mononucleated cardiomyocytes in PR fetuses. Whilst mononucleated and binucleated cardiomyocytes were smaller, the relative size of cardiomyocytes when expressed relative to heart weight was larger in PR compared to Control fetuses. The increase in the relative proportion of mononucleated cardiomyocytes and the relative sparing of the growth of individual cardiomyocytes in the growth restricted fetus are adaptations which may have long term consequences for heart development in postnatal life. Key words: Fetus , hypoxia, hypertrophy, hyperplasia, cardiomyocyte.

Am J Physiol Regul Integr Comp Physiol