Journal of Indian Association of Pediatric Surgeons
Journal of Indian Association of Pediatric Surgeons
                                                   Official journal of the Indian Association of Pediatric Surgeons                           
Year : 2019  |  Volume : 24  |  Issue : 2  |  Page : 97--99

Anatomical explanations of the pathogenesis of proximal hypospadias


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

Correspondence Address:
Prof. Smail Acimi
Department of Visceral Surgery, Faculty of Medicine, Children's Hospital Canastel, University of Oran, Oran
Algeria

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.



How to cite this article:
Acimi S. Anatomical explanations of the pathogenesis of proximal hypospadias.J Indian Assoc Pediatr Surg 2019;24:97-99


How to cite this URL:
Acimi S. Anatomical explanations of the pathogenesis of proximal hypospadias. J Indian Assoc Pediatr Surg [serial online] 2019 [cited 2021 Apr 18 ];24:97-99
Available from: https://www.jiaps.com/text.asp?2019/24/2/97/253340


Full Text



 Introduction



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



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



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}{Figure 2}

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}

 Discussion



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 disappearingIn 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 fibrosisIn 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 fibrosisThe 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}

 Conclusion



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

1Acimi S. What is the pathogenesis of proximal hypospadias? Turk J Urol 2018;44:357-61.
2Acimi S, Acimi MA. Can we preserve the urethral plate in proximal hypospadias repair? Ann Plast Surg 2017;79:68-72.
3Acimi 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.
4Beleza-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.
5Vaysse P, Moscovici J. Hypospadias. Epidemiology of hypospadias. 1st ed. Montpellier: Sauramps Médical. 2003. p. 24-244.
6Carmichael 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.
7North 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.
8Dulauroy 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.