To better understand how the human fetal penis and clitoris grows and remodels, we undertook an investigation to define active areas of cellular proliferation and programmed cell death spatially and temporally during development of human fetal external genitalia from the indifferent stage (8 weeks) to 18 weeks of gestation. Fifty normal human fetal penile and clitoral specimens were examined using macroscopic imaging, scanning electron microscopy and immunohistochemical localization for the cellular proliferation and apoptotic markers, Ki67 and Caspase-3, respectively. A number of hot spots of cellular proliferation characterized by Ki67 localization are present in the penis and clitoris especially early in development, most notably in the corporal body, glans, remodeling glanular urethra, the urethral plate, the roof of the urethral groove and the fully formed penile urethra. The 12-fold increase in penile length over 10 weeks of growth from 8 to 18 weeks of gestation based on Ki67 labelling appears to be driven by cellular proliferation in the corporal body and glans. Throughout all ages in both the developing penis and clitoris Ki67 labeling was consistently elevated in the ventral epidermis and ventral mesenchyme relative to the dorsal counterparts. This finding is consistent with the intense morphogenetic activity/remodeling in the ventral half of the genital tubercle in both sexes involving formation of the urethral/vestibular plates, canalization of the urethral/vestibular plates and fusion of the urethral folds to form the penile urethra. Areas of reduced or absent Ki67 staining include the urethral fold epithelium that fuses to form the penile tubular urethra. In contrast, the urethral fold mesenchyme is positive for Ki67. Apoptosis was rarely noted in the developing penis and clitoris; the only area of minimal Caspase-3 localization was in the epithelium of the ventral epithelial glanular channel remodeling.

为了更好地了解人类胎儿阴茎和阴蒂如何生长和重塑，我们进行了一项调查，以定义人类胎儿外生殖器从无差异期（8周）到18周的发育过程中，在空间和时间上定义细胞增殖的活跃区域和程序性的细胞死亡。妊娠 使用宏观成像，扫描电子显微镜和免疫组织化学定位检查了五十个正常人胎儿的阴茎和阴蒂标本，以分别检测细胞增殖和凋亡标记物Ki67和Caspase-3。在阴茎和阴蒂中，尤其是在发育的早期，存在着许多以Ki67定位为特征的细胞增殖热点，最明显的是在身体，龟头，重塑肾小管，尿道板，尿道沟的顶部和完全形成的阴茎尿道。基于Ki67标记，从妊娠8周到18周，在10个星期的生长中，阴茎长度增加了12倍，这似乎是由体液和龟头中的细胞增殖驱动的。在发育中的阴茎和阴蒂的所有年龄段中，相对于背侧对应者，腹侧表皮和腹侧间充质的Ki67标记一直持续升高。这一发现与两性在生殖器结节的腹侧中强烈的形态发生活性/重塑是一致的，涉及形成尿道/膀胱板，尿道/膀胱板的导管化以及尿道皱褶融合形成阴茎尿道。Ki67染色减少或不存在的区域包括融合形成阴茎管状尿道的尿道折叠上皮。相反，尿道折叠间充质对于Ki67呈阳性。发育中的阴茎和阴蒂很少出现细胞凋亡。Caspase-3最小定位的唯一区域是在腹侧上皮肾小球通道重塑的上皮中。