Effects of stress during pregnancy on hepatic glucogenic capacity in rat dams and their fetuses.

Stress during pregnancy is associated with metabolic dysfunction in the adult offspring in human and other animals. However, little is known about the metabolic effects of pregnancy stress on the mothers and fetuses during pregnancy itself. This study aimed to determine the consequences of the common experimental procedures of injection and single housing in pregnant rats on fetal and maternal hepatic glucogenic capacities. On day (D) 20 of pregnancy, feto-placental weights and the glycogen content and activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) of fetal and maternal liver were measured in rats pair or single housed from D1 with or without saline injection from D15 to D19. Housing and saline injection both affected hepatic glucogenic capacity. In maternal liver, saline injection but not housing reduced glycogen content and raised G6Pase activity, whereas housing but not treatment increased PEPCK activity. In fetuses, housing and injection interacted in regulating PEPCK activity and reducing hepatic glycogen content and placental weight. Body weight was decreased and hepatic G6Pase increased by injection but not housing in the fetuses. Single-housed dams ate less than those pair-housed near term while saline injection elevated maternal plasma corticosterone concentrations. Thus, single housing and saline injection are both stresses during rat pregnancy that alter feto-placental weight and hepatic glucogenic capacity of the fetuses and dams near term. Routine experimental procedures per se may, therefore, have consequences for offspring hepatic phenotype as well as modifying the outcomes of dietary and other environmental challenges during pregnancy.

Role of leptin in the regulation of growth and carbohydrate metabolism in the ovine fetus during late gestation.

Leptin is an important regulator of appetite and energy expenditure in adulthood, although its role as a nutritional signal in the control of growth and metabolism before birth is poorly understood. This study investigated the effects of leptin on growth, carbohydrate metabolism and insulin signalling in fetal sheep. Crown-rump length-measuring devices and vascular catheters were implanted in 12 sheep fetuses at 105-110 days of gestation (term 145 +/- 2 days). The fetuses were infused i.v. either with saline (0.9% NaCl; n = 6) or recombinant ovine leptin (0.5-1.0 mg kg(-1) day(-1); n = 6) for 5 days from 125 to 130 days when they were humanely killed and tissues collected. Leptin receptor mRNA and protein were expressed in fetal liver, skeletal muscle and perirenal adipose tissue. Throughout infusion, plasma leptin in the leptin-infused fetuses was 3- to 5-fold higher than in the saline-infused fetuses, although plasma concentrations of insulin, glucose, lactate, cortisol, catecholamines and thyroid hormones did not differ between the groups. Leptin infusion did not affect linear skeletal growth or body, placental and organ weights in utero. Hepatic glycogen content and activities of the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the leptin-infused fetuses were lower than in the saline-infused fetuses by 44, 48 and 36%, respectively; however, there were no differences in hepatic glycogen synthase activity or insulin signalling protein levels. Therefore, before birth, leptin may inhibit endogenous glucose production by the fetal liver when adipose energy stores and transplacental nutrient delivery are sufficient for the metabolic needs of the fetus. These actions of leptin in utero may contribute to the development of neonatal hypoglycaemia in macrosomic babies of diabetic mothers.