Prenatal administration of dexamethasone during early pregnancy negatively affects placental development and function in mice1

Abstract

Prenatal treatment of dexamethasone, a synthetic stress hormone, leads to low birth weight and affects adult pathophysiology. Because fetal growth and survival are critically dependent on successful placental development, we aimed to investigate the effects of prenatal dexamethasone exposure on placental growth and function, particularly focusing on issues surrounding the time of stress exposure in a developmental context. Dexamethasone was administered at a dosage of 1 mg/kg BW (DEX1) or 10 mg/kg BW (DEX10) intraperitoneally at gestational d 7.5, 8.5, and 9.5 in pregnant mice. Placentas were then dissected at gestational d 11.5 and 18.5. Placental size and weight were reduced at d 11.5 in a dose-dependent manner (P = 0.11 for saline vs. DEX1 and P < 0.001 for DEX1 vs. DEX10 in size; P = 0.34 for saline vs. DEX1 and P < 0.01 for DEX1 vs. DEX10 in weight). In contrast, a considerable heterogeneity was shown at d 18.5, especially in DEX10-treated mice. Some placentas were small and malformed whereas some were enlarged with structural abnormalities in spongiotrophoblasts and labyrinth layers. Although placental overgrowth under such condition seemed to compromise fetal demand for nutrient supply, disorganized cell structure with reduced fetal vasculature observed in large placentas suggests that prenatal stress exposure during the early gestational period negatively affects placental development and efficiency.