Embryology of the Penis




(1)
Pediatric Surgery, Al Azher University, Cairo, Egypt

 



Abstract

Understanding normal human genital and urethral development is the first step in unraveling both rare and common congenital penile anomalies, and to draw a proper plan of reconstruction.

Despite the high incidence of congenital malformations of the anorectal and urogenital systems in humans, the mechanisms that govern normal anogenital development are still poorly understood.


Keywords
Genital tubercleLabioscrotal swellingCloacaUrogenital sinusUrethral foldsOptical projection tomography


In both male and female human embryos, development of the external genitalia begins with the emergence of the paired genital swellings immediately above the cloaca, as a very low conical eminence between the umbilical cord and the base of the tail in the 9 mm embryo (7 weeks gestation). These swellings fuse medially and give rise to the bipotential genital tubercle, which can be masculinized to form the penis or feminized to form the clitoris. As the genital tubercle grows out, the ventral side of the cloacal endoderm forms a bilaminar urethral plate that extends into the genital tubercle, and this structure later cavitates in a proximal to distal direction to form the urethral tube.

The lower urinary tract LUT and genital tubercle GT have distinct embryological origins, as the LUT develops from the endodermal cloaca, which becomes separated into the urogenital sinus and rectum by the downgrowth of the urorectal septum (Fig. 1.1).

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Fig. 1.1
Progression of the urorectal fold to divide the cloaca into urogenital sinus and rectum

The urogenital sinus gives rise to the internal urethra and bladder, while both become lined with a water-tight urothelial layer, these two regions differentiate into distinct structures with respect to musculature, stroma, epithelial layers and innervation. GT gives rise to the male and female external genitalia (penis, clitoris and foreskin) and represents the intersection between the reproductive and urinary tracts. A second set of swellings, the labioscrotal swellings, arise later in development and give rise to the scrotum and labia majora in males and females, respectively. The LUT and GT physically intersect as the urethra passes through the GT, which proposed to be derived from all three germ layers. UP is derived from urethral endoderm (Fig. 1.2).

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Fig. 1.2
Indifferent external genitalia in a 48 days fertilization age, GL glandular portion, CO corporal portion of the former genital tubercle, UR urethral groove originated from the urethral plate, LS labioscrotal swelling. The external opening of the urogenital sinus is marked with an arrow

The GT surface other than the urethral plate is derived from surface ectoderm and the core of the extending appendage is derived from lateral plate mesoderm. Without a urethral plate, the GT will fail to form, as we can see in most cases of aphallia where usually there is no urethra or even a urinary meatus (Chap. 8). The urethral epithelium of the GT does not grow out from the urethra but forms in situ along the GT itself. GT development involves an early androgen-independent phase and a later androgen-dependent phase, after which sexual dimorphism is evident [1].

Male accessory organs, such as the prostate and the bulbourethral glands, originate from endodermal buds of the urogenital sinus growing into a specific urogenital mesenchyme.

The genital tubercle develops as an out-budding appendage, hence it has been proposed that there is congruence in the genetic basis of GT patterning with other out-budding appendages, including the limb and craniofacial prominences, and this could explain coexistence of multiple genitourinary anomalies with limb and extremities anomalies in different syndromes [2].


1.1 Penile Development


Several signaling cascades control reproductive organogenesis and this is a versatile system to study how hormones regulate organ growth and differentiation. Some molecular pathways have been identified in initial anlagen formation as well as later hormone driven development. These include fibroblast growth factor (FGF), hedgehog (HH), Wnt, transforming growth factor (TGF) signals and other “effector” genes [3].

Between the 4th and 7th weeks of gestation, the mesodermal mesenchyme migrates to the cranial aspect of the cloacal membrane to form the genital tubercle. The cloacal membrane itself is composed of two layers: endoderm and ectoderm. The caudal portion of the cloacal membrane develops into urogenital folds. These structures are the precursors for external genitalia in both males and females. The Y chromosome initiates male differentiation through the SRY gene and other genes, which triggers testicular development, through signaling the differentiation of primitive sex cords into testes by first signaling the development of Sertoli cells, these cells then aid in the development of germ cells and Leydig cells within the testes. Leydig cells produce testosterone, which is converted to dihydrotestosterone by the enzyme 5α-reductase, to induce external genitalia development through androgen receptors. Under the influence of androgens produced by the testes, external genitalia then develop into the penis and scrotum. Any disruption of androgen function at this stage will results in defective development of urethra to be presented as a divergent forms of hypospadias, or defective penile development, with feminine external genitalia, as in cases of Androgen Insensitivity Syndrome [4].

The genital tubercle becomes longer and out of it forms the penis. The urethral folds also lengthen ventrally, between these extends the urogenital sinus and forms the urethral groove, which is lined with endoderm. The floor of this sulcus thickens through epithelial proliferation and forms the urethral plate that temporarily fills it out (Fig. 1.3).
Jun 30, 2017 | Posted by in UROLOGY | Comments Off on Embryology of the Penis

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