Urethral seam formation and hypospadias
Urethral seam formation and hypospadias
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DOI：
10.1007/s004410000345
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发表时间：
2001-09-01
影响因子：
3.6
通讯作者：
Cunha, GR
中科院分区：
文献类型：
--
作者：
Baskin, LS;Erol, A;Cunha, GR
了解正常男性尿道的形成可以阐明尿道下裂的病因。我们描述了小鼠尿道的形成，展示了与人类尿道发育的相似性和相关性，并介绍了尿道形成过程中上皮缝形成和重塑的概念。三种机制可能解释上皮缝的形成：（1）类似于腭架融合中描述的上皮-间质转化，（2）细胞凋亡，和/或（3）通过细胞迁移的组织重塑。通过组织学、免疫组织化学和三维重建，将小鼠胚胎（妊娠 14-21 天）的尿道发育与人类胚胎标本（妊娠 8-16 周）的尿道形成进行比较。尿道是由尿道皱襞的上皮边缘融合形成的，形成中线上皮缝。上皮缝通过细胞迁移到位于尿道中央和腹侧移位的上皮细胞残余物而被重塑。上皮接缝通过在其中点附近变窄而被重塑，随后上皮迁移到尿道或阴茎皮肤中。上皮细胞被间充质细胞取代。该重塑接缝显示出与间充质细胞相对应的凋亡活性窄带（大约 30 μm 宽），而不是与上皮细胞相对应。没有证据表明细胞角蛋白和间充质标记物（肌动蛋白或波形蛋白）共表达。尿道缝形成发生在小鼠和人类身上。我们在小鼠中的数据支持这样的假设：接缝转化是通过细胞迁移而不是通过上皮间质转化或上皮细胞凋亡发生的。我们假设上皮融合、重塑和细胞迁移的破坏导致尿道下裂。
Knowledge of the formation of the normal male urethra may elucidate the etiology of hypospadias. We describe urethral formation in the mouse, show the similarities and relevance to human urethral development, and introduce the concept of the epithelial seam formation and remodeling during urethral formation. Three mechanisms may account for epithelial seam formation: (1) epithelial-mesenchymal transformation similar to that described in the fusion of the palatal shelves, (2) apoptosis, and/or (3) tissue remodeling via cellular migration. Urethral development in the embryonic mouse (14-21 days of gestation) was compared with urethral formation in embryonic human specimens (8-16 weeks of gestation) by using histology, immunohistochemistry, and three-dimensional reconstruction. The urethra forms by fusion of the epithelial edges of the urethral folds, giving a midline epithelial seam. The epithelial seam is remodeled via cellular migration into a centrally located urethra and ventrally displaced remnant of epithelial cells. The epithelial seam is remodeled by narrowing approximately at its midpoint, with subsequent epithelial migration into the urethra or penile skin. The epithelial cells are replaced by mesenchymal cells. This remodeling seam displays a narrow band (approximately 30 mum wide) of apoptotic activity corresponding to the mesenchymal cells and not to epithelial cells. No evidence was seen of the co-expression of cytokeratin and mesenchymal markers (actin or vimentin). Urethral seam formation occurs in both the mouse and the human. Our data in the mouse support the hypothesis that seam transformation occurs via cellular migration and not by epithelial mesenchymal transformation or epithelial apoptosis. We postulate that disruption of epithelial fusion, remodeling, and cellular migration leads to hypospadias.