In utero prednisone exposure affects genital development

Area of Science:

• Developmental biology
• Toxicology
• Urology

Background:

• The etiology of hypospadias is unknown, but maternal asthma exposure is a potential risk factor.
• Mouse and human urethral development share similarities, making mice a suitable model for studying urethral formation.
• Prednisone's effects on urethral development may involve weak androgenic activity or testosterone suppression.

Purpose of the Study:

• To investigate the effects of prednisone on urethral formation in a mouse model.
• To determine if prednisone exposure during gestation influences urethral development and the risk of hypospadias.

Main Methods:

• Timed pregnant C57/6 mice were exposed to varying doses of prednisone (100-1000 mg/kg) on gestational days 12-18.
• Genital tubercles of male and female fetuses were examined on day 19 using histology and 3D reconstruction.
• Specific focus was placed on the developing urethral seam and its fusion process.

Main Results:

• Supraphysiological prednisone doses (1000 mg/kg) arrested urethral seam formation in approximately 25% of male fetuses.
• Lower prednisone doses (100 and 200 mg/kg) accelerated urethral fold fusion and elongated the urethral tube in males.
• No significant changes in urethral formation were observed in female fetuses across all tested prednisone dosages.

Conclusions:

• Supraphysiological prednisone doses inhibit urethral fold fusion, potentially leading to hypospadias in male mouse fetuses.
• Low doses of prednisone accentuate urethra formation in males without causing hypospadias or affecting females.
• These findings suggest a dose-dependent effect of prednisone on male urethral development.