Prenatal exposure to maternal low protein diet suppresses replicative potential of myocardial cells

Abstract

Background and aims We have previously shown that a maternal low protein (LP) diet during pregnancy results in severe depression of neonatal heart contractility due, in part, to an increase in apoptotic loss of cardiomyocytes. The aim of this study was to examine if maternal LP diet would alter replicative potential of neonatal myocardial cells. Methods and results We determined the effect of maternal LP and normal diet (90 and 180 g/casein/kg respectively) on relative numbers of mitotic myocardial cells in male offspring at birth and at 7–28 days post-partum. Myocardial cells undergoing mitosis were identified by dual-immunofluorescence of cardiac sections for cardiac muscle myosin and phosphorylated histone 3, whereas cells within the cell cycle were identified by immunoreactivity for Ki67 at 14–28 days post-partum. Neonates from control dams displayed the expected gradual decline in mitotic cells from birth to 28 days post-partum. Hearts from LP offspring had lower numbers of mitotic cells at birth, compared to controls, suggestive of subnormal muscle cell numbers at that stage. When placed in normal diet, LP offspring developed increased myocardial mitosis at 7 days compared to controls, which normalized to control levels at 21–28 days post-partum. An increase in Ki67-positive myocardial cells was also observed in the LP exposed group at 28 days of age. Conclusion Maternal LP diet suppresses myocardial replicative potential and this likely contributes to reduced cell numbers at birth. This suppression is lifted by a protein-replete diet which stimulates post-natal replication of myocardial cells and likely results in a catching-up in cell numbers.