The development of the male genitourinary system: II. The origin and formation of the urethral plate

Hynes, Patrick; Fraher, John

doi:10.1016/j.bjps.2003.08.018

Cited by 51 publications

(40 citation statements)

References 16 publications

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“…21 By contrast, in mice the urethral plate appears to canalize directly to form most of the penile urethra. [32][33][34] nonetheless, a subtle ventral penile raphe is evident in the adult mouse penis (Figure 4a). raphes are adult manifestations of fetal fusion events; however, the exact origin and importance of the mouse ventral penile raphe has yet to be explained.…”

Section: 31mentioning

confidence: 99%

“…Prenatally, the penile urethra develops within the genital tubercle, presumably via canalization of the urethral plate to form most of the penile urethra. [32][33][34] Postnatally, the urethral meatus forms via fusion of elements that constitute the urethral meatus. 35,36 this fusion process is inferred from raphes, midline clefts and processes that define the adult mouse urethral meatus (Figures 4a and 5a-c).…”

Section: 31mentioning

confidence: 99%

“…Postnatal formation of the mouse urethral meatus appears to involve multiple epithelial fusion events and, therefore, differs substantially from prenatal urethral development within the shaft of the glans. [32][33][34] in adulthood the mouse urethral meatus is located distally, where the MuMP joins the MuMP ridge ( Figures 3 and 7a, b). thus, the mouse urethral meatus forms post natally via fusion of the MuMP with the MuMP ridge (Figures 5a, b).…”

Section: 31mentioning

confidence: 99%

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Current understanding of hypospadias: relevance of animal models

et al. 2015

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| Hypospadias is a congenital abnormality of the penile urethra with an incidence of approximately 1:200-1:300 male births, which has doubled over the past three decades. The aetiology of the overwhelming majority of hypospadias remains unknown but appears to be a combination of genetic susceptibility and prenatal exposure to endocrine disruptors. Reliable animal models of hypospadias are required for better understanding of the mechanisms of normal penile urethral formation and hence hypospadias. Mice and/ or rats are generally used for experimental modelling of hypospadias, however these do not fully reflect the human condition. To use these models successfully, researchers must understand the similarities and differences between mouse, rat and human penile anatomy as well as the normal morphogenetic mechanisms of penile development in these species. Despite some important differences, numerous features of animal and human hypospadias are shared: the prevalence of distal penile malformations; disruption of the urethral meatus; disruption of urethra-associated erectile bodies; and a common mechanism of impaired epithelial fusion events. Rat and mouse models of hypospadias are crucial to our understanding of hypospadias to ultimately reduce its incidence through better preventive strategies.

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Section: 31mentioning

confidence: 99%

Section: 31mentioning

confidence: 99%

Section: 31mentioning

confidence: 99%

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Current understanding of hypospadias: relevance of animal models

et al. 2015

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“…Cavitation of the bilaminar urethral plate epithelium progresses from proximal to distal, resulting in a cylindrical urethral tube (Van Der Werff et al, 2000;Hynes and Fraher, 2004;Cohn, 2011). Our finding that Fgfr2 EndoΔ mutants fail to develop a penile urethral lumen suggests that cavitation requires endodermal Fgfr2 activity.…”

Section: Discussionmentioning

confidence: 78%

Tissue-specific roles of Fgfr2 in development of the external genitalia

2015

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Congenital anomalies frequently occur in organs that undergo tubulogenesis. Hypospadias is a urethral tube defect defined by mislocalized, oversized, or multiple openings of the penile urethra. Deletion of Fgfr2 or its ligand Fgf10 results in severe hypospadias in mice, in which the entire urethral plate is open along the ventral side of the penis. In the genital tubercle, the embryonic precursor of the penis and clitoris, Fgfr2 is expressed in two epithelial populations: the endodermally derived urethral epithelium and the ectodermally derived surface epithelium. Here, we investigate the tissue-specific roles of Fgfr2 in external genital development by generating conditional deletions of Fgfr2 in each of these cell types. Conditional deletion of Fgfr2 results in two distinct phenotypes: endodermal Fgfr2 deletion causes mild hypospadias and inhibits maturation of a complex urethral epithelium, whereas loss of ectodermal Fgfr2 results in severe hypospadias and absence of the ventral prepuce. Although these cell type-specific mutants exhibit distinctive genital anomalies, cellular analysis reveals that Fgfr2 regulates epithelial maturation and cell cycle progression in the urethral endoderm and in the surface ectoderm. The unexpected finding that ectodermal deletion of Fgfr2 results in the most severe hypospadias highlights a major role for Fgfr2 in the developing genital surface epithelium, where epithelial maturation is required for maintenance of a closed urethral tube. These results demonstrate that urethral tubulogenesis, prepuce morphogenesis, and sexually dimorphic patterning of the lower urethra are controlled by discrete regions of Fgfr2 activity.

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“…17 Incomplete fusion of the embryonic urethral folds and failure of canalization of the glandular urethra have been believed for a long time to be the only explanation for the occurrence of hypospadias in man. [18][19][20] Recently, this urethral anomaly has been attributed to defective development of a complex of fascial and vascular tissues proximal to the urethral orifice. This tissuecomplex normally proliferates to form the ventrum of the penile shaft and to push the urethral orifice distally.…”

Section: Pathoembryology Of Hypospadias and Chordeementioning

confidence: 99%

Pathoembryology of Hypospadias and Chordee

Haroun¹

2018

MOJAP

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Hypospadias is one of the most common congenital anomalies in childhood. It refers to displacement of the external urethral meatus toward the undersurface of penis, the scrotum or the perineum. Congenital abnormal curvature of the penis is termed as "chordee" and it may be dorsal or ventral and of varying degree. Genetic as well as environmental antiandrogenic and estrogenic factors are blamed for the etiology of congenital penile malformations. Morphological patterns of prepuce and of dartos tissue are described. In some instances, preoperative treatment with testosterone is indicated. Different surgeries are mentioned for the repair of hypospadias, penile torsion and chordee.

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The development of the male genitourinary system: II. The origin and formation of the urethral plate

Cited by 51 publications

References 16 publications

Current understanding of hypospadias: relevance of animal models

Current understanding of hypospadias: relevance of animal models

Tissue-specific roles of Fgfr2 in development of the external genitalia

Pathoembryology of Hypospadias and Chordee

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