IUGR impairs cardiomyocyte growth and maturation in fetal sheep.

Placental insufficiency causes intrauterine growth restriction (IUGR), a common complication of pregnancy. In skeletal muscle, IUGR reduces fetal myofibril size, reduces myoblast proliferation and reduces expression of genes in cell cycle regulation clusters. The myocardium is striated like skeletal muscle, and IUGR also reduces cell cycle activity and maturation in cardiomyocytes, despite cardiac output preferentially directed to the coronary circulation.

Increased fetal insulin concentrations for one week fail to improve insulin secretion or β-cell mass in fetal sheep with chronically reduced glucose supply.

Maternal undernutrition during pregnancy and placental insufficiency are characterized by impaired development of fetal pancreatic β-cells. Prolonged reduced glucose supply to the fetus is a feature of both. It is unknown if reduced glucose supply, independent of other complications of maternal undernutrition and placental insufficiency, would cause similar β-cell defects.

Chronic late-gestation hypoglycemia upregulates hepatic PEPCK associated with increased PGC1alpha mRNA and phosphorylated CREB in fetal sheep.

Hepatic glucose production is normally activated at birth but has been observed in response to experimental hypoglycemia in fetal sheep. The cellular basis for this process remains unknown. We determined the impact of 2 wk of fetal hypoglycemia during late gestation on enzymes responsible for hepatic gluconeogenesis, focusing on the insulin-signaling pathway, transcription factors, and coactivators that regulate gluconeogenesis.