Uda Akiko, Kojima Yoshiyuki, Hayashi Yutaro, Mizuno Kentaro, Asai Nobuaki, Kohri Kenjiro
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
J Urol. 2004 Mar;171(3):1362-6. doi: 10.1097/01.ju.0000100140.42618.54.
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.
我们三维观察了实验性尿道下裂大鼠模型中外生殖器的形成过程。
从妊娠第14天至20天，每天给自然受孕的雌性Sprague-Dawley大鼠腹腔注射7.5毫克氟他胺（一种雄激素受体阻滞剂），以建立尿道下裂大鼠模型。对照组由未接触氟他胺的雄性后代组成。在妊娠第17.5、19.5和21.5天获取胎儿阴茎。我们通过扫描电子显微镜观察它们。
在17.5天大的胚胎中，对照大鼠阴茎腹侧从阴茎基部到冠状沟可见突起。这一发现表明尿道从阴茎基部向冠状沟发育。另一方面，尿道下裂大鼠未观察到这种突起，阴茎腹侧也未见尿道。在19.5天大的胚胎中，对照大鼠阴茎近端出现腹侧包皮闭合，而尿道下裂大鼠未出现。在对照大鼠中，阴囊在会阴处可辨认，并被一条中隔褶（阴囊缝）分开。阴囊缝延伸至阴茎基部，与覆盖尿道的包皮褶相连。另一方面，尿道下裂大鼠没有阴囊缝，阴茎基部的凹陷似乎形成了未来的尿道开口。在21.5天大的胚胎中，对照大鼠的包皮完全包裹阴茎远端，而尿道下裂大鼠的包皮背侧呈帽状，腹侧有裂隙，外观类似于人类阴茎阴囊型尿道下裂的形态。
该尿道下裂大鼠模型对于进一步研究阴茎生长和分化以及尿道下裂中外生殖器形成的分子机制具有重要价值。
