INVESTIGATIVE UROLOGY

The impact of prenatal androgens on vaginal and urogenital sinus development in the female mouse
Yucel S, Cavalcanti AG, Wang Z, Baskin LS
From the Department of Urology and Pediatrics, University of California-San Francisco Children’s Medical Center, University of California-San Francisco, San Francisco, California, USA
J Urol. 2003; 170: 1432-36

• 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.
  
  
• Editorial Comment
  It is well known that the development of the male and female internal and external genitalia is dependent on a complex interaction of specific androgenic and nonandrogenic hormones. In this elegant experimental morphological study, the authors analyzed whether the level of the vaginal confluence with the urogenital sinus moves proximal from perineum to bladder neck as a function of prenatal androgen exposure in a mouse model.
  The authors found that prenatal exposure to increasing levels of androgen causes a dose dependent change in the confluence of the urogenital sinus and vagina. They observed in this mouse model, a distal elongation of the common urogenital sinus and proximal migration of the bladder neck in respect to the fixed bony structures of the pubic arch. Although the molecular basis of urogenital sinus elongation and migration remains unexplained, the authors speculated that the complex hormonal environment found in patients with congenital adrenal hyperplasia or other abnormalities leading to androgen excess can result in wide spectrum anatomical variations of the vaginal confluence in the urogenital sinus.

Dr. Francisco J.B. Sampaio
Full-Professor and Chief, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil