A physiological increase in maternal cortisol alters uteroplacental metabolism in the pregnant ewe

摘要

Fetal nutrition is determined by maternal availability, placental transport and uteroplacental metabolism of carbohydrates. Cortisol affects maternal and fetal metabolism, but whether maternal cortisol concentrations within the physiological range regulate uteroplacental carbohydrate metabolism remains unknown. This study determined the effect of maternal cortisol infusion (1.2mgkg(-1)day(-1) i.v. for 5days, n=20) on fetal glucose, lactate and oxygen supplies in pregnant ewes on day approximate to 130 of pregnancy (term=145days). Compared to saline infusion (n=21), cortisol infusion increased maternal, but not fetal, plasma cortisol (P<0.05). Cortisol infusion also raised maternal insulin, glucose and lactate concentrations, and blood pH, PCO2 and HCO3- concentration. Although total uterine glucose uptake determined by Fick's principle was unaffected, a greater proportion was consumed by the uteroplacental tissues, so net fetal glucose uptake was 29% lower in cortisol-infused than control ewes (P<0.05). Concomitantly, uteroplacental lactate production was >2-fold greater in cortisol- than saline-treated ewes (P<0.05), although uteroplacental O-2 consumption was unaffected by maternal treatment. Materno-fetal clearance of non-metabolizable [H-3]methyl-d-glucose and placental SLC2A8 (glucose transporter 8) gene expression were also greater with cortisol treatment. Fetal plasma glucose, lactate or -amino nitrogen concentrations were unaffected by treatment although fetal plasma fructose and hepatic lactate dehydrogenase activity were greater in cortisol- than saline-treated ewes (P<0.05). Fetal plasma insulin levels and body weight were also unaffected by maternal treatment. During stress, cortisol-dependent regulation of uteroplacental glycolysis may allow increased maternal control over fetal nutrition and metabolism. However, when maternal cortisol concentrations are raised chronically, prolonged elevation of uteroplacental lactate production may compromise fetal wellbeing.