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ORIGINAL ARTICLE
Year : 2019  |  Volume : 24  |  Issue : 2  |  Page : 97-99
 

Anatomical explanations of the pathogenesis of proximal hypospadias


Department of Visceral Surgery, Faculty of Medicine, Children's Hospital Canastel, University of Oran, Oran, Algeria

Date of Web Publication1-Mar-2019

Correspondence Address:
Prof. Smail Acimi
Department of Visceral Surgery, Faculty of Medicine, Children's Hospital Canastel, University of Oran, Oran
Algeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaps.JIAPS_247_17

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   Abstract 


Aims: The aim of this study was to try to explain the pathogenesis of proximal hypospadias based on anatomical and histological findings.
Methods: During 9 years, we performed systematic biopsies (in the lateral areas of the urethral plate, as well as under this plate) in 81 patients treated for proximal hypospadias. The histological study was performed by routine coloring, hematoxylin and eosin, and Masson's trichrome, which colors the collagen fibers in blue, and monoclonal antibody against alpha-smooth muscle actin.
Results: There is a fibrosis tissue abnormally present on the ventral side of the penis. This tissue consists of a mixture of fibrous connective tissue, nerve nets, short vessels, and smooth muscle fibers. The penis' dartos does not contain smooth muscle fibers. These fibers can come from a blood vessel or spongy tissue which existed during the neonatal period in the distal part of the penis before disappearing.
Conclusions: The proximal hypospadias is due presumably to avascular necrosis of the distal part poorly vascularized of the corpus spongiosum.


Keywords: Chordee, curvature, etiology, hypospadias, pathogenesis, proximal hypospadias


How to cite this article:
Acimi S. Anatomical explanations of the pathogenesis of proximal hypospadias. J Indian Assoc Pediatr Surg 2019;24:97-9

How to cite this URL:
Acimi S. Anatomical explanations of the pathogenesis of proximal hypospadias. J Indian Assoc Pediatr Surg [serial online] 2019 [cited 2019 May 27];24:97-9. Available from: http://www.jiaps.com/text.asp?2019/24/2/97/253340





   Introduction Top


The term hypospadias is a Greek word composed of two words: hypo (νπο) which mean under and spathe (σπαδη) which mean sword.[1] It is due to the defect of distal corpus spongiosum and urethra. Thus, hypospadias is characterized by ectopia of the urethral meatus, a meatus located on the ventral side of the penis or on the scrotal area.

Hypospadias represents the most common urogenital malformation in boys. Its proximal forms represent approximately one-third of cases and are very often associated with curvature.[2] The essential factor responsible for this curvature is the fibrosis tissue present on the ventral side of the penis.[3] However, when the initial curvature is >90°, a short urethral plate becomes the main cause of this curvature.[2]

The pathogenesis of proximal hypospadias associated with curvature remains unknown.

The present study tries to explain the pathogenesis of proximal hypospadias, associated with curvature, based on anatomical and histological findings encountered in patients treated for this urogenital malformation.


   Methods Top


From January 2009 to December 2017, we have performed biopsies (in the lateral areas of the urethral plate, as well as under this plate) in 81 patients treated for proximal hypospadias associated with curvature. These biopsies were made during the different steps of the curvature correction. The histological studies of these biopsies were performed in only one laboratory by routine coloring, hematoxylin and eosin (H and E: HE, HE1, and HE2), and Masson's trichrome, which colors the collagen fibers in blue, and monoclonal antibody against alpha-smooth muscle actin.

In all patients, we have performed on the ventral face of the penis from 4 to 6 removals of tissue for a histological study. These biopsies were made in three distinct areas: in the lateral area of the urethral plate, under the urethral plate, and in the proximal region of the urethral plate and upstream from the meatus. These removals of tissue for biopsies followed the different stages of the correction of curvature: the first removals of tissue were realized after the releasing of the skin and dartos fascia and the second under urethral plate after its possible mobilization.[2]

The age of the patients who underwent the surgery ranged from 9 to 56 months (mean 29 months).


   Results Top


The biopsies revealed an abnormal presence of the fibrous tissue in the ventral side of the penis. This tissue consists of a mixture of fibrous connective tissue, nerve nets, short vessels, and smooth muscle fibers. Thus, the routine coloring by H and E (HE, HE1, and HE2) shows the smooth muscle bundles, clearly visible, within the fibrous tissue [Figure 1]. The presence of fibrous tissue was confirmed with Masson's trichrome which colors the collagen fibers in blue [Figure 2].
Figure 1: Biopsy made on the ventral side of the penis (in the lateral areas of the urethral plate). The routine coloring by hematoxylin and eosin shows the fibrous tissue with (collagen fibrosis) with some fibroblast cells and smooth muscle fibers (H and E, ×100)

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Figure 2: The use of Masson's trichrome shows collagen fibers in blue

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The use of a monoclonal antibody against alpha-smooth muscle actin revealed the presence of the smooth muscle in 47 patients (58% of cases). These smooth muscle fibers take a brown color [Figure 3].
Figure 3: (a and b) The use of a monoclonal antibody against alpha-smooth muscle actin revealed the presence of the smooth muscle fibers (which shows the smooth muscle fibers in brown) (a, ×100 and b, ×400)

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   Discussion Top


Several etiologies of hypospadias have been suggested: genetic etiology by abnormalities of genes which regulate the secretion of androgens and fibroblast growth factor genes (FGF8 gene, FGF10 gene, and FGF2 gene);[4] endocrine etiology of maternal origin (especially progestin and estrogens[5] and corticosteroids); and toxic etiology by substances which interfere with the endocrine system of the fetus such as dioxins, organochlorine pesticides,[6] and phytoestrogens in vegetarian women.[7] However, the pathogenesis of hypospadias remains unknown.

Some factors lead us to believe that the proximal hypospadias and curvature are due to avascular necrosis of the distal part poorly vascularized of the corpus spongiosum, immediately after its individualization from the rest of mesenchymal tissue (between 4th and 5th month of pregnancy). This necrosis is probably the cause of the disorderly development of the single artery of this body (during the transition from a state of two arteries to only one):

  • The presence of the smooth muscle fibers into fibrosis tissue abnormally presents on the ventral side of the penis. In contrast to the dartos' scrotum, the penis' dartos does not contain smooth muscle fibers. These smooth muscle fibers can come from a blood vessel or spongy tissue which existed during the neonatal period in the distal part of the penis before disappearing
  • In case of ischemic necrosis of a delimited area in a solid organ by obstruction of a terminal artery, the tissue of this area is gradually transformed into fibrosis with the retraction of the lesion area. Thus, the formation of this fibrosis on the ventral side of the penis of a fetus in rapid growth is at the origin of a curvature of the penis whose degree will depend on the precocity of the appearance of this fibrosis
  • In addition, French researchers have discovered pathological fibroblasts, responsible for an overproduction collagens, and thus of significant scar tissue.[8] This type of fibroblast only exists in the fetus, which assumes that the cicatrization in a fetus is always complicated by fibrosis
  • The virilization of the external genitalia occurs using dihydrotestosterone between the 12th and 14th weeks of gestation: The genital tubercle elongates considerably, the labioscrotal folds merge in the midline to form the scrotum, and the urethral gutter is closed from behind by a phenomenon of endodermal tubulization. After the 14th week, the fusion of the labioscrotal folds cannot occur even under intense androgenic stimulation. Although the phallic growth can be induced, the penile urethra completely formed at the 14th week has a blind end and reaches the base of the glans, while the balanic part of the urethra is formed secondarily by ectodermal intussusceptions in the 4th month. At the same time that the penile urethra forms, the mesenchymal tissue which surrounds it becomes denser and forms the roughing of the corpus spongiosum; however, the transformation of the mesenchymal tissue to erectile tissue occurs only secondarily, between the 4th and 5th month of pregnancy. However, in some cases of hypospadias, the presence upstream of the urethral meatus, of a bifurcation of corpus spongiosum into two branches [Figure 4]. This supposes that the corpus spongiosum is formed by fusion around the urethra of two mesenchymal bodies. In addition, the final arterial system is formed before the 9th week of gestation; this assumes that the arterial supply of this purely masculine formation (corpus spongiosum) originates from a new vascularization probably developed under androgens secretion (angiogenic substances in target tissues).
Figure 4: The corpus spongiosum divided into two branches

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   Conclusion Top


The presence of the smooth muscle fibers in fibrosis tissue, abnormally present on the ventral side of the penis, in patients treated for proximal hypospadias associated with curvature supposes that the proximal form of hypospadias is due to avascular necrosis of the distal part of the corpus spongiosum.

Acknowledgment

I would like to thank Dr. M. Laghouati, who performed the histological study of biopsies, Pathology Laboratory, Dar el Beida, Oran, Algeria.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Acimi S. What is the pathogenesis of proximal hypospadias? Turk J Urol 2018;44:357-61.  Back to cited text no. 1
    
2.
Acimi S, Acimi MA. Can we preserve the urethral plate in proximal hypospadias repair? Ann Plast Surg 2017;79:68-72.  Back to cited text no. 2
    
3.
Acimi S, Boukli-Hacene A. Interest of mobilization of the urethral plate in the release of chordee related to posterior hypospadias. Prog Urol 2005;15:59-62.  Back to cited text no. 3
    
4.
Beleza-Meireles A, Lundberg F, Lagerstedt K, Zhou X, Omrani D, Frisén L, et al. FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias. Eur J Hum Genet 2007;15:405-10.  Back to cited text no. 4
    
5.
Vaysse P, Moscovici J. Hypospadias. Epidemiology of hypospadias. 1st ed. Montpellier: Sauramps Médical. 2003. p. 24-244.  Back to cited text no. 5
    
6.
Carmichael SL, Ma C, Werler MM, Olney RS, Shaw GM; National Birth Defects Prevention Study. Maternal corticosteroid use and hypospadias. J Pediatr 2009;155:39-44, 44.e1.  Back to cited text no. 6
    
7.
North K, Golding J. A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC study team. Avon longitudinal study of pregnancy and childhood. BJU Int 2000;85:107-13.  Back to cited text no. 7
    
8.
Dulauroy S, Di Carlo SE, Langa F, Eberl G, Peduto L. Lineage tracing and genetic ablation of ADAM12(+) perivascular cells identify a major source of profibrotic cells during acute tissue injury. Nat Med 2012;18:1262-70.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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