Morphological Features of External Genitalia in Hypospadiac Rat Model: 3-Dimensional Analysis

Abstract

We examined 3-dimensionally the process of external genitalia formation in the experimental hypospadiac rat model. We administered 7.5 mg flutamide daily, a blocker of androgen receptor, into the abdomen of naturally pregnant female Sprague-Dawley rats from gestational days 14 to 20 to produce a hypospadiac rat model. The control group consisted of male offspring not exposed to flutamide. The fetal phallus was obtained at gestational days 17.5, 19.5 and 21.5. We observed them by scanning electron microscopy. In the 17.5-day-old embryo the projection on the ventral side of the phallus was observed from the base of the phallus to the coronary sulcus in the control rat. This finding demonstrated that the urethra develops from the base of the phallus to the coronary sulcus. On the other hand, this projection was not observed in the hypospadiac rat and the urethra was not seen on the ventral side of the phallus. In the 19.5-day-old embryo the ventral preputial closure appeared in the proximal phallus of the control rat but not of the hypospadiac rat. In the control rat the scrotum was discerned in the perineum and divided by a median fold (the raphe). The raphe reached the base of the phallus, where it was concurrent with the preputial fold that covers the urethra. On the other hand, the hypospadiac rat did not have a raphe and the hollow at the base of the phallus appeared to give rise to the future orifice of the urethra. In the 21.5-day-old embryo the control rat prepuce completely surrounded the distal phallus, whereas that of the hypospadiac rat was dorsally hooded with a ventral cleft and the external appearance resembled the morphology of human penoscrotal hypospadias. This hypospadiac rat model is considered valuable for further studying penile growth and differentiation, and the molecular mechanisms in external genitalia formation in hypospadias.