Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA, 94143, USA.
Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA, 94143, USA.
Differentiation. 2023 May-Jun;131:1-26. doi: 10.1016/j.diff.2023.02.001. Epub 2023 Feb 10.
Female mice were treated for 35 days from birth to 60 days postnatal (P0, [birth], P5, P10, P20 and adult [∼P60]) with dihydrotestosterone (DHT). Such treatment elicited profound masculinization the female external genitalia and development of penile features (penile spines, male urogenital mating protuberance (MUMP) cartilage, corpus cavernosum glandis, corporal body, MUMP-corpora cavernosa, a large preputial space, internal preputial space, os penis). Time course studies demonstrated that DHT elicited canalization of the U-shaped clitoral lamina to create a U-shaped preputial space, preputial lining epithelium and penile epithelium adorned with spines. The effect of DHT was likely due to signaling through androgen receptors normally present postnatally in the clitoral lamina and associated mesenchyme. This study highlights a remarkable male/female difference in specification and determination of urogenital organ identity. Urogenital organ identity in male mice is irreversibly specified and determined prenatally (prostate, penis, and seminal vesicle), whereas many aspects of the female urogenital organogenesis are not irreversibly determined at birth and in the case of external genitalia are not irreversibly determined even into adulthood, the exception being positioning of the female urethra, which is determined prenatally.
从出生到产后 60 天（P0[出生]、P5、P10、P20 和成年[约 P60]），雌性小鼠接受二氢睾酮（DHT）治疗 35 天。这种治疗会使雌性外生殖器发生深刻的男性化，并发育出阴茎特征（阴茎棘、雄性泌尿生殖交配隆起（MUMP）软骨、海绵体腺、海绵体体、MUMP-海绵体、大包皮腔、内部包皮腔、阴茎骨）。时程研究表明，DHT 诱导 U 形阴蒂阴唇的管化，形成 U 形包皮腔、包皮衬里上皮和装饰有棘的阴茎上皮。DHT 的作用可能是通过雄激素受体信号传递，这些受体通常在产后存在于阴蒂阴唇和相关的间质中。这项研究强调了雌雄生殖器官身份的规范和决定存在显著的性别差异。雄性小鼠的泌尿生殖器官身份在产前（前列腺、阴茎和精囊）是不可逆地确定和决定的，而雌性泌尿生殖器官发生的许多方面在出生时并不是不可逆地确定的，在外部生殖器的情况下甚至在成年时也不是不可逆地确定的，例外是女性尿道的定位，它是在产前确定的。
