Pregnant women at risk of preterm delivery are administered potent synthetic glucocorticoids (betamethasone, dexamethasone) to reduce neonatal mortality should preterm delivery ensue. This precedes the natural rise in endogenous glucocorticoids shortly prior to parturition. However, studies in animals and humans suggest that glucocorticoid exposure may adversely affect fetal and placental outcomes, dependent on timing. We hypothesise that in mice, dexamethasone will differentially affect fetal and placental growth and development if administered prior to the rise in endogenous fetal glucocorticoid synthesis (initiates at embryonic day [E]14.5) versus exposure at peak endogenous glucocorticoid concentration (E16.5-E17.5).
Female C57BL/6 mice were time-mated (day of plug designated E0.5) and received an IP injection of vehicle (Veh) or dexamethasone (Dex; 500μg/kg) at E13.5 or E16.5 (n=4-11/group). A control group (Con) received no injection, controlling for stress of procedure. In vivo ultrasound scanning was conducted 24h post-injection at E14.5 or E17.5, respectively, to measure umbilical arterial blood flow (a key regulator of fetal and placental growth) and fetal heart function. Dams were sacrificed immediately after the scan. Fetal and placental weights were recorded, and tissues collected. Data were analysed by ANOVA with post-hoc Tukey’s test. Mean ± SEM; #p<0.05 vs Veh; *p<0.05, ***p<0.001 vs Con.
24h treatment with dexamethasone significantly reduced fetal weight at E14.5 (Dex: 0.22±0.01g#/***, Veh: 0.25±0.01g, Con: 0.29±0.02g, n=4-11); placental weight did not differ. At E17.5, fetal weight was unaffected by dexamethasone treatment but placental weight was significantly reduced (Dex: 0.077±0.001g*, Veh: 0.083±0.003g, Con: 0.083±0.001g, n=9-11).
Dexamethasone injection differentially affected fetal and placental growth at E14.5 and E17.5 in a reciprocal manner. Analysis of ultrasound data is ongoing to determine alterations in placental hemodynamic function following dexamethasone treatment. Future experiments will analyse placental morphology and molecular pathways to develop a comprehensive understanding of how these parameters translate to function of dexamethasone exposed placentas.