Molecular and genetic regulation of testis descent and external genitalia development

Abstract

Testicular descent as a prerequisite for the production of mature spermatozoa and normal external genitalia morphogenesis, and therefore facilitating copulation and internal fertilization, are essential developmental steps in reproduction of vertebrate species. Cryptorchidism, the failure of testis descent, and feminization of external genitalia in the male, usually in the form of hypospadias, in which the opening of the urethra occurs along the ventral aspect of the penis, are the most frequent pediatric complications. Thus, elucidating the molecular mechanisms involved in the regulation of testis descent and the formation of external genitalia merits a special focus. Natural and transgenic rodent models have demonstrated both morphogenic processes to be under the control of a plethora of genetic factors with complex time-, space-, and dose-restricted expression pattern. The review elucidates the molecular mechanisms involved in the regulation of testis descent and the formation of external genitalia and, wherever possible, assesses the differences between these rodent animal models and other mammalian species, including human.

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins

“…We were particularly interested in this element because gene expression and function in the limbs and face are often linked. Indeed, it has been postulated that development of the face shares many regulatory circuits in common with appendages such as the limbs and genitalia (Yamaguchi et al, 1999;Yamada et al, 2003;Klonisch et al, 2004;Cobb and Duboule, 2005). In this report, we have shown that two conserved regions of the intron work together to yield high levels of expression in the face and limbs.…”

Estrogen receptor-α mediates estrogen-inducible abnormalities in the developing penis

“…It is also known that dihydrotestosterone, a 5a-reductase reduced testosterone metabolite, is more critical than testosterone in development of those organs which are derived from the urogenital sinus, genital tubercle, and genital swelling in males, including the penis (Anderson & Clark 1990, George & Wilson 1994. Notably, the early differentiation and morphogenesis of male reproductive organs corresponds to the testosterone surge by fetal Leydig cells that occurs at about 12 weeks of gestation in humans (Williams-Ashman & Reddi 1991, George & Wilson 1994, Klonisch et al 2004 and at late gestation and early neonatal period in rodents (Ward & Weisz 1984, El-Gehani et al 1998. Alterations in androgenic activity during the critical period of differentiation, resulting from abnormalities in testosterone, 5a-reductase, or androgen receptor, cause maldevelopment of internal and external male genitalia, including hypospadias and shorter penis (Gray et al 2001, Sultan et al 2001, Kim et al 2002, Foster & Harris 2005.…”

Development of the Gubernaculum During Testicular Descent in the Rat

“…In addition, the timing of testicular descent varies, with both phases occurring prenatally in humans compared with inguinoscrotal migration occurring postnatally in rodents. The different anatomy of the gubernaculum and its contained cremaster muscle in rodents versus humans has been highlighted recently by Klonisch et al (2004). However, most of the key features of the mechanism of descent are similar, secondary to evolution with minor differences from a common ancestor.…”