Alteration of Cytokine/Chemokine Transcript Levels in the Placenta of Humanized Mouse Models Treated Prenatally With Dexamethasone.

Abstract

BACKGROUND: Dexamethasone (DEX) is used during pregnancies at risk of early delivery or congenital adrenal hyperplasia. DEX exposure is also known to cause placental damage. Although placental cytokines/chemokines protect the fetus and regulate placental development, few studies have examined placental cytokine/chemokine transcript levels in DEX-dosed pregnant mice. METHODS: To examine this, quantitative PCR and histological analysis in humanized mice were performed. Mice were injected once daily for five consecutive days with DEX (5 mg/kg) or saline (0.9%) via the tail vein on gestation days (GDs) 10-14, respectively (n = 3-5). All mice were intravenously injected with human immunoglobulin G (2 mg/kg) on GD14. RESULTS: No statistically significant changes in maternal body weights by GD 12, absolute or relative placental weights in the dosed group were observed compared to concurrent controls. Fetal weights in the DEX-dosed group were lower than in concurrent controls, and statistically significant changes were observed on GD 18. Necrosis/apoptosis of cytotrophoblasts in the placenta's labyrinth zone was observed in the DEX-dosed dams. The placental transcript levels of interferon lambda receptor 1, interleukin 6, and C-X-C motif chemokine ligand 10 (Cxcl10) were higher in the DEX-dosed than the control group on GDs 15 and 16; the difference of Cxcl10 transcript level was statistically significant (p = 0.016) on GD 16. CONCLUSIONS: Cxcl10 is overexpressed during DEX-induced placental damage in the mouse models, suggesting it as a potential biomarker of placental damage. Further studies are needed to confirm Cxcl10 changes during placental damage induced by other placental toxicants.