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

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.