PLACEBO-CONTROLLED, BLINDED COMPARISON OF ANTENATAL BETAMETHASONE ON MOUSE LIVER DEVELOPMENT

Abstract

The objective of this investigation was to evaluate, in a placebo-controlled manner, the developing mouse liver after antenatal exposure either to a single dose or to a multidose of betamethasone. Ninety gravid CD-1 mice were randomly divided into three groups (n = 30/group) to receive either saline (0.25 mL sc) or betamethasone (0.10 mg sc) as a single dose on gestational day (GD) 14 of a 19-day gestation or as a 0.10 mg dose given twice daily on GD 14 and on GD 15 (4 doses). GD 0 is defined by the presence of a copulatory plug. These exposures of betamethasone cause fetal mouse lung maturation as would be observed in premature humans at 24–34 weeks of gestation. The livers were removed either from the fetuses on GD 16.5 or from the offspring on postnatal day 1, 3, 5, and 120. Special stains were used to evaluate hepatocyte architecture, glycoprotein and glycogen content, extramedullary hematopoiesis and iron storage. Hepatocyte intranuclear DNA content, cell size, and cell shape were measured by image analysis (CAS 200). At GD 16.5, betamethasone produced a significant decrease in the liver/body weight ratio that, when compared with the placebo group, was greater with the multidose (p < 0.01) than with the single dose (p < 0.05). 16.5 GD single dose hepatocytes were smaller in size as compared to placebo without impact on intranuclear DNA (p < 0.01). Single dose PND 1 hepatocytes demonstrated an increase in intranuclear DNA as compared to placebo but without change in cell size (p < 0.001). The prenatal reduced liver weight recovered in the newborn period. No difference in microscopic architecture of the hepatocytes or histologic differences between either of the three treatment groups was found in glycogen deposition, extramedullary hematopoiesis or iron metabolism at GD 16.5 and postnatally. It was concluded antenatal betamethasone can cause a decrease in the liver/body weight ratio in the fetal mouse that recovers eventually without any functional impact as assessed histologically.