Division of Clinical and Functional Anatomy, Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.
Ann Anat. 2013 Dec;195(6):586-95. doi: 10.1016/j.aanat.2013.09.004. Epub 2013 Oct 16.
The female urethra has often been neglected in previous studies on the development of the human urogenital system. Our aim has been to reach a consensus on the organogenesis of the female urethra and the vagina with respect to interactions between the epithelia with different evolutionary origins. Therefore we tried to clarify open questions on the spatiotemporal distribution of molecular markers raised against mesenchymal and epithelial structures within the developing human female urethra. Furthermore, we draw comparisons regarding gender-specific aspects in urethral development. To this effect, we used molecular markers such as different cytokeratins (CKs), p63, Ki67, uroplakin III, E-cadherin, vimentin, smooth muscle actin (SMA), cleaved caspase 3 and paired box gene 2 (PAX 2) to phenotype developmental changes. Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay was additionally performed to reveal apoptosis. We examined different gestational stages starting from week (W) 8 until W 15. Immunohistochemistry showed a distinct staining pattern for p63 and CK17, both markers for stem cells, ensuing from the urogenital sinus (UGS) proceeding into the Muellerian duct (MD). This was observed throughout development and might be a stimulus for the formation of the vaginal anlagen that derive from the MD. In the attachment area of the MD we detected a conglomeration of cells with different embryonic origins. The epithelium of the UGS became transitional at W 9 after fertilization, and the differentiation advanced in a cranial to caudal direction. The paraurethral glands showed a slightly different staining profile than the urethral epithelium, which may be able to explain why carcinomas of these structures display various histological appearances. In addition, we could show that during the development of the female urogenital system the primary incidence is the formation of the urethra. This is followed by the establishment of the vagina, which clearly depends on the proper differentiation of the UGS/urethra.
女性尿道在先前的人类泌尿生殖系统发育研究中经常被忽视。我们的目标是就具有不同进化起源的上皮细胞之间的相互作用达成女性尿道和阴道的器官发生共识。因此，我们试图阐明有关在人女性尿道发育过程中针对间充质和上皮结构的分子标记物的时空分布的悬而未决的问题。此外，我们就尿道发育的性别特异性方面进行了比较。为此，我们使用了分子标记物，例如不同的细胞角蛋白（CK）、p63、Ki67、尿路上皮蛋白 III、E-钙黏蛋白、波形蛋白、平滑肌肌动蛋白（SMA）、裂解半胱天冬酶 3 和配对盒基因 2（PAX 2）来表型发育变化。末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）测定法另外用于揭示细胞凋亡。我们检查了从第 8 周到第 15 周的不同妊娠阶段。免疫组织化学显示 p63 和 CK17 的染色模式明显不同，这两种标记物都是来自泌尿生殖窦（UGS）的干细胞标志物，随后进入苗勒管（MD）。这在整个发育过程中都观察到，可能是形成源自 MD 的阴道原基的刺激因素。在 MD 的附着区，我们检测到来自不同胚胎起源的细胞聚集。UGS 的上皮在受精后第 9 周变成过渡型，并且分化从颅向尾方向进行。尿道旁腺显示出与尿道上皮略有不同的染色模式，这可能能够解释为什么这些结构的癌显示出各种组织学表现。此外，我们能够表明，在女性泌尿生殖系统的发育过程中，原发性事件是尿道的形成。随后是阴道的建立，这显然依赖于 UGS/尿道的适当分化。
