The impact of prenatal androgens on vaginal and urogenital sinus development in the female mouse.

PURPOSE

In females abnormal urogenital virilization can occur secondary to prenatal exposure to exogenous or endogenous androgens. We studied the effects of different doses of prenatal androgens on urogenital sinus development and the location of the vaginal confluence in a mouse model.

MATERIALS AND METHODS

Timed pregnant C57/6 mice were exposed to 2, 5 and 10 mg testosterone propionate on gestational days 14 through 18. On gestational day 19 the genital tubercles and internal genitalia were examined grossly and histologically for the presence of virilization. Three-dimensional computer reconstruction was done and plastic cast injection molds of the urogenital sinus were made in select specimens.

RESULTS

Microscopic analysis confirmed the spectrum of virilization, which occurred in 98% of testosterone propionate treated female fetuses. Plastic cast injection showed that affected females had a longer urogenital sinus, more proximal confluence and shorter vagina in a dose dependent manner. Histological sections and 3-dimensional reconstruction revealed that the bladder neck moved proximal under the pubic bone, also in a dose dependent manner.

CONCLUSIONS

Prenatal exposure to increasing levels of androgen causes urogenital sinus elongation in a female mouse fetus. In the mouse model the confluence area moves proximally together with the bladder neck in a dose dependent manner.