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Comparative teratogenicity of selected glucocorticoids applied ocularly in mice
Abstract:
Three glucocorticoids (dexamethasone, hydrocortisone, and prednisolone), were ocularly applied to pregnant CD-1 mice on days 10-13 of gestation. The drug concentrations were various multiples of the common therapeutic dose levels and were applied to both eyes in 1 microliter drops five times a day. Eighteen-day fetuses were examined for malformations. A significant increase in the incidence of cleft palate was observed in fetuses treated with each of these glucocorticoids. There appeared to be a dose related effect on cleft palate width among fetuses from both dexamethasone and prednisolone treated dams. The incidence of sex organ anomalies, although lower than the incidence of cleft palate, also showed a positive dose relationship. Analysis of variance was used to compare the teratogenic effects of these glucocorticoids ocularly applied in equipotent anti-inflammatory concentrations. Our results indicate that dexamethasone produces a higher incidence of cleft palate, than either of the other two drugs when given in equipotent concentrations. It appears that the teratogenic potency of these ocularly applied glucocorticoids cannot be predicted on the basis of anti-inflammatory potency.
Insights
Ocular glucocorticoid exposure during pregnancy, including dexamethasone, hydrocortisone, and prednisolone, significantly increased cleft palate incidence in mouse fetuses. Dexamethasone showed the highest teratogenic potency, suggesting anti-inflammatory potency does not predict teratogenic effects.
Area of Science:
- Pharmacology
- Developmental Toxicology
- Teratology
Background:
- Glucocorticoids are widely used medications with known anti-inflammatory and immunosuppressive properties.
- Concerns exist regarding potential teratogenic effects of glucocorticoids, particularly with ocular exposure during critical developmental periods.
- Understanding the comparative teratogenic potential of different glucocorticoids is crucial for risk assessment in pregnant individuals.
Purpose of the Study:
- To investigate and compare the teratogenic effects of three commonly used glucocorticoids: dexamethasone, hydrocortisone, and prednisolone.
- To determine if ocular application of these drugs during gestation leads to fetal malformations, specifically cleft palate and sex organ anomalies.
- To assess the dose-response relationship and compare the teratogenic potency of equipotent anti-inflammatory concentrations of these glucocorticoids.
Main Methods:
- Pregnant CD-1 mice were administered ocular drops of dexamethasone, hydrocortisone, and prednisolone at varying multiples of therapeutic doses on days 10-13 of gestation.
- Eighteen-day fetuses were examined for external and internal malformations, with a focus on cleft palate and sex organ anomalies.
- Statistical analysis, including analysis of variance, was employed to compare the incidence and severity of teratogenic effects.
Main Results:
- All three tested glucocorticoids significantly increased the incidence of cleft palate in the exposed fetuses.
- A positive dose-related effect was observed for cleft palate width and sex organ anomalies with dexamethasone and prednisolone.
- Dexamethasone demonstrated a higher incidence of cleft palate compared to hydrocortisone and prednisolone when administered at equipotent anti-inflammatory concentrations.
Conclusions:
- Ocular application of dexamethasone, hydrocortisone, and prednisolone during critical periods of mouse gestation can induce teratogenic effects, notably cleft palate.
- The teratogenic potency of these ocularly applied glucocorticoids does not correlate with their anti-inflammatory potency.
- Dexamethasone exhibits a stronger teratogenic effect on palate development than hydrocortisone and prednisolone at equivalent anti-inflammatory doses, highlighting the need for careful consideration of glucocorticoid choice during pregnancy.