Embryonic development of mouse external genitalia: insights into a unique mode of organogenesis

Abstract

The mammalian external genitalia are specialized appendages for efficient copulation, internal fertilization and display marked morphological variation among species. In this paper, we described the embryonic development of mouse genital tubercle (GT), an anlage of the external genitalia utilizing the scanning electron microscope (SEM) analysis. It has been shown that the Distal Urethral Epithelium (DUE) may fulfill an essential role in the outgrowth control of the GT. Our present SEM analysis revealed a small distal protrusion at the tip of the GT of normal embryos as well as some morphological differences between male and female embryonic external genitalia. Previous analysis shows that the teratogenic dose of Retinoic Acid (RA) induces a drastic marformation of the urethral plate, but not gross abnormalities for GT outgrowth. Interestingly, a small distal protrusion at the tip of GT was clearly observed also after RA treatement. Furthermore, we showed that treatment with anti-androgen flutamide resulted in the demasculinization of the GT in males. The unique character of GT development and the sexual dimorphism are discussed.

Regulation of outgrowth and apoptosis for the terminal appendage:external genitalia: development by concerted actions of BMP signaling

“…GT initiates from the cloaca region forming as a bud-anlage from 10.5 dpc and continues to differentiate throughout the perinatal period (Suzuki et al, 2002;Yamada et al, 2003). A coordinated mode of development of the caudal embryonic region including the cloaca, tail gut and VER (ventral ectodermal ridge) has been reported previously (Goldman et al, 2000;Miller and Briglin, 1996).…”

“…The first morphological alteration indicative of GT outgrowth occurs at 10.5 days post coitum (dpc) in the mouse and continues throughout the perinatal period (Suzuki et al, 2002). Several growth factors, including FGF proteins, sonic hedgehog (SHH) and WNT have been implicated in the control of external genitalia development in mice (Haraguchi et al, 2000;Haraguchi et al, 2001;Perriton et al, 2002;Yamaguchi et al, 1999).…”

Molecular genetic cascades for external genitalia formation: An emerging organogenesis program

“…Evidence supporting the crucial role of androgen is based on pharmacological and genetic data. Androgen antagonists (Silversides et al, 1995;Suzuki et al, 2002) or inhibitors of its synthesis (Imperato-McGinley et al, 1985;Clark et al, 1990) interfere with testicular function and external genitalia development. Mutations in androgen receptor gene (Murakami, 1987;Yeh et al, 2002;Sato et al, 2003) or for androgen synthetic enzymes (Andersson et al, 1991;Wilson, 1992) result in abnormalities in male sexual differentiation and development.…”

Comparative analysis of genes downstream of the Hoxd cluster in developing digits and external genitalia

“…WISH using embryos fixed in 4% paraformaldehyde was performed according to standard procedures. Because sex-specific differences in external genitalia only begin to appear at E16.5 (Suzuki et al, 2002), the sex of embryos was not routinely determined. Nevertheless, in some cases the gender of embryos was determined by PCR as described (Lavrovsky et al, 1998) to confirm that the expression patterns were not sex-dependent.…”