Kurzrock E A, Jegatheesan P, Cunha G R, Baskin L S
Departments of Urology and Anatomy, University of California San Francisco, San Francisco, California, USA.
J Urol. 2000 Nov;164(5):1786-92.
To determine whether the development of the rabbit phallus would be an appropriate model of human phallic development, we evaluated the formation of the fetal rabbit phallus and attempted to induce hypospadias pharmacologically.
New Zealand rabbit fetuses were obtained on gestational days 20 to 24, 26, 28 and 31. Sex was determined by gonadal morphology, and 6 fetuses were obtained at each age. The perineum was dissected, fixed, sectioned and stained with hematoxylin and eosin, and monoclonal antibodies against neuronal specific enolase. Two pregnant rabbits were treated with 10 mg./kg. finasteride orally daily between gestational days 19 and 28. The development of the external genitalia was compared in treated and untreated control rabbits.
The rabbit phallus contains 2 corpora cavernosa and dorsolateral nerves similar to the human. In male and female fetuses fusion of the urethral folds progressed in a proximal to distal sequence forming a seam at the point of ventromedial fusion. In male fetuses urethral fold and ventral preputial fusion continued more distally toward the glans compared to females. Thus, in mature males the urethral meatus and ventral prepuce extended to the tip of the phallus, whereas in females the urethral meatus opened on the proximal phallus and the prepuce was deficient ventrally forming a dorsal hood. Male offspring had a significantly larger anogenital distance postnatally than female offspring. In male fetuses exposed to finasteride urethral fusion did not extend distally and the prepuce was deficient ventrally. Also, male offspring exposed to finasteride in utero had a significantly shorter anogenital distance than females and untreated control males at all ages (p <0.05).
Fetal development of the rabbit phallus and urethra is homologous to the human. Although the gestational period is significantly shorter, the temporospatial pattern of external genitalia development is analogous in these species. Feminization of the rabbit urethra, hypospadias, can be induced by inhibiting 5alpha-reductase. Use of this animal model will allow further study of molecular mechanisms involved in urethral fusion and the evaluation of the pathophysiological processes of hypospadias.
为了确定兔阴茎的发育是否会是人类阴茎发育的合适模型，我们评估了胎兔阴茎的形成，并试图通过药理学方法诱导尿道下裂。
在妊娠第20至24天、26天、28天和31天获取新西兰兔胎儿。通过性腺形态确定性别，每个年龄段获取6只胎儿。解剖会阴，固定，切片，并用苏木精和伊红以及抗神经元特异性烯醇化酶的单克隆抗体染色。两只怀孕兔子在妊娠第19至28天期间每天口服10mg/kg非那雄胺。比较经处理和未经处理的对照兔子的外生殖器发育情况。
兔阴茎包含两条海绵体和与人类相似的背外侧神经。在雄性和雌性胎儿中，尿道褶的融合从近端向远端进行，在腹内侧融合点形成一条缝。与雌性相比，雄性胎儿的尿道褶和腹侧包皮融合在向龟头的方向上更向远端延伸。因此，在成熟雄性中，尿道口和腹侧包皮延伸到阴茎顶端，而在雌性中，尿道口在阴茎近端开口，包皮在腹侧缺失，形成一个背侧帽。雄性后代出生后的肛殖距明显大于雌性后代。在暴露于非那雄胺的雄性胎儿中，尿道融合未向远端延伸，包皮在腹侧缺失。此外，子宫内暴露于非那雄胺的雄性后代在所有年龄段的肛殖距均明显短于雌性和未经处理的对照雄性（p<0.05）。
兔阴茎和尿道的胎儿发育与人类同源。尽管妊娠期明显较短，但这些物种中外生殖器发育的时空模式相似。抑制5α-还原酶可诱导兔尿道女性化及尿道下裂。使用这种动物模型将有助于进一步研究尿道融合所涉及的分子机制，并评估尿道下裂的病理生理过程。
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