BackgroundTo examine the mechanism of urethral seam formation during embryonal development of rat urethra.MethodsTime-mated Sprague-Dawley rats were killed and the genital tubercles of male pups harvested on embryonic day (ED) 15, 16, 18, and 19. External morphology was observed under scanning electron microscope. Serial transverse sections were prepared to examine dynamic changes in the urethral seam morphology with hematoxylin-eosin staining, immunohistochemistry, transmission electron microscopy, and double immunofluorescence.ResultsBilateral outgrowth of urethral swelling followed by urethral plate fusion in the midline to form urethral seam was observed from ED 16 onwards. Coexpression of epithelial and mesenchymal markers was observed in several cells at the urethral seam; a few cells with coexpression of epithelial and apoptotic markers were also observed. Mesenchymal transformation of epithelial cells and apoptotic epithelial cells was observed under transmission electron microscope.ConclusionUrethral formation occurs by tubulogenesis, which initiates proximally and progresses distally. This is the first study to demonstrate epithelial-mesenchymal transformation and epithelial cell apoptosis in the urethral seam cells of fetal rats. These findings provide new insights into the mechanisms involved in embryonal development of the urethra.