Wang Shanshan, Shi Mingxin, Zhu Dongqing, Mathews Ranjiv, Zheng Zhengui
Department of Physiology, School of Medicine, Southern Illinois University Carbondale, Carbondale, IL.
Department of Physiology, School of Medicine, Southern Illinois University Carbondale, Carbondale, IL; Department of Pharmacy, Jiangsu Food & Pharmaceutical Science College, Huai'an, Jiangsu Province, China.
Urology. 2018 Mar;113:179-186. doi: 10.1016/j.urology.2017.11.002. Epub 2017 Nov 16.
To determine whether the guinea pig phallus would be an appropriate model of human penile development, we characterized the embryology and sexual differentiation of guinea pig external genitalia and attended to induce hypospadias in males and tubular urethra formation in females pharmacologically.
The external genitalia of guinea pig were collected from genital swelling initiation to newborn stages, and scanning electronic microscopy and histology were performed to visualize the morphology and structure. Immunohistochemistry was used to determine the androgen receptor localization. Bicalutamide and methyltestosterone were given to pregnant dams to reveal the role and timing of androgen in guinea pig penile masculinization.
Canalization and dorsal-to-ventral movement of the urethral canal develops the urethral groove in both sexes, and then the males perform distal-opening-proximal-closing to form tubular urethra. More nuclear-localized androgen receptor is found in proximal genital tubercles of males than in females at (E) 29. Antiandrogen treatment at E26-E30 can cause hypospadias, and methyltestosterone administration at E27-E31 can induce tubular urethra formation in females.
Fetal development of the guinea pig phallus is homologous to that of humans. Although guinea pig has structures similar to mouse, the urethral groove and the tubular urethra formation are more similar to humans. Antiandrogen treatment causes hypospadias in males and additional androgen induces tubular urethra formation in females. Thus, guinea pig is an appropriate model for further study of cellular and molecular mechanisms involved in distal-opening-proximal-closing in tubular urethra formation and the evaluation of the pathophysiological processes of hypospadias.
为了确定豚鼠阴茎是否为人类阴茎发育的合适模型，我们对豚鼠外生殖器的胚胎学和性分化进行了特征描述，并试图通过药理学方法诱导雄性尿道下裂和雌性管状尿道形成。
收集豚鼠从生殖器肿胀开始到新生阶段的外生殖器，进行扫描电子显微镜检查和组织学检查以观察形态和结构。采用免疫组织化学法确定雄激素受体的定位。给怀孕的母鼠注射比卡鲁胺和甲基睾酮，以揭示雄激素在豚鼠阴茎男性化中的作用和时机。
两性尿道管的管道化和从背侧到腹侧的移动形成了尿道沟，然后雄性进行远端开口近端闭合以形成管状尿道。在胚胎期第29天，雄性近端生殖结节中发现的核定位雄激素受体比雌性更多。在胚胎期第26 - 30天进行抗雄激素治疗可导致尿道下裂，在胚胎期第27 - 31天给予甲基睾酮可诱导雌性形成管状尿道。
豚鼠阴茎的胎儿发育与人类同源。虽然豚鼠具有与小鼠相似的结构，但尿道沟和管状尿道的形成与人类更相似。抗雄激素治疗导致雄性尿道下裂，额外的雄激素诱导雌性形成管状尿道。因此，豚鼠是进一步研究管状尿道形成中远端开口近端闭合所涉及的细胞和分子机制以及评估尿道下裂病理生理过程的合适模型。
