Prenatal dexamethasone exposure exerts sex-specific effect on placental oxygen and nutrient transport ascribed to the differential expression of IGF2

Background: Clinical studies have showed that dexamethasone exposure during pregnancy could cause fetal growth retardation, but the mechanism by which prenatal dexamethasone exposure influences placental nutrient transport is still unclear. This study investigated the impacts of prenatal dexamethasone on the placental oxygen and nutrient transport. Methods: Pregnant Wistar rats were subcutaneously administered with dexamethasone from day 9 to day 20 of gestation at 0.2 or 0.8 mg/kg.d. Pregnant rats were sacrificed on gestational day 20. The placental tissue was collected for analysis. Results: Prenatal dexamethasone exposure (PDE) declined the fetal weight and increased the intrauterine growth retardation (IUGR) rate in a dose-dependent manner. The total placental volume and the length, density and surface area of fetal capillaries in the labyrinth zone reduced in a dose-dependent manner. In addition, the thickness of syncytial membrane dose-dependently increased, resulting in a dose-dependent decrease in oxygen diffusion capacity. Furthermore, after PDE, the nutrient transport area and oxygen diffusion capacity of male placenta were lower than that of female placenta. The mRNA and protein expression of placental nutrient transporters including glucose transporter 1 (GLUT1), glucose transporter 3 (GLLYT3), L-type amino acid transporter 1 (LAT1), lipoprotein lipase (LPL) and scavenger receptor class B type 1 (SRB1) increased in female placenta. However, in male placenta, the expression of LAT1, LPL and SRB1 was significantly decreased and GLUT1 and GLUTS have a decrease trend. We further investigated the expression of insulin-like growth factor 1 (IGF1) and insulin-like growth factor 2 (IGF2) related to placental and fetal growth and development. Our study showed that the expression of IGFI was significantly decreased both in male and female placentas after PDE. But the expression of IGF2 was significantly increased in female placentas while significantly decreased in male placentas. Conclusions: Our study shows prenatal dexamethasone exposure exerts sex-specific influence on the placental oxygen and nutrient transport. This might be ascribed to the differential expression of IGF2 after PDE. These findings provide evidence on the dexamethasone-induced toxicity to the placenta and fetal development.