Abstract
Concomitant with the rupture of the cloacal membrane in the 6th week of development, the intermediate layer of the perineal-skin epithelium thickens. We investigated its distribution and the development of the corresponding subcutaneous compartments in serial sections of female human embryos and foetuses and prepared 3D reconstructions to establish topographic relations. The thick-skin area becomes restricted to the outlets of the genital and intestinal tracts. The clitoris and labia majora become identifiable at ~7 weeks. The mesenchymal mass inside the clitoris soon divides into the glans and the cavernous bodies. The clitoral hood forms between 10 and 14 weeks as a fold of tissue that extends from proximal to distal over the glans. Due to the caudal bending of the clitoral shaft, the labia majora gradually cover the clitoris after ~14 weeks. The labia minora form at ~8 weeks from the ridges of thick-skin epithelium that flank the genital exit. They are continuous ventrolaterally with the clitoral hood and ventromedially with the apex of the cavernous body. Dorsally, their dense subcutaneous mesenchymal core extends to the anal canal. Between 8 and 14 weeks, the urethra lengthens axially, while the vaginal vestibule extends ventrally. In this period, the urethral plate of female embryos is mitotically active but does not increase in volume, which suggests that it contributes to vestibular growth. In conclusion, we observed a temporal correlation between the development of the thick-skin epithelium and that of the external genitals, with a distribution that is reminiscent of the dihydrotestosterone-sensitive skin.