Abstract

BackgroundHypospadias are among the most common genital malformations. Langerhans Cells (LCs) play a pivotal role in HIV and HPV infection. The migration of LC precursors to skin coincides with the embryonic period of hypospadias development and genetic alterations leading to the formation of hypospadias impact the development of ectodermally derived tissues. We hypothesized that this might be associated with a difference in frequency or morphology of epidermal and dermal LCs in hypospadias patients.MethodsA total of 43 patients from two centers were prospectively included into this study after parental consent and ethics approval. Epidermal and dermal sheets were prepared from skin samples of 26 patients with hypospadias, 13 patients without penile malformations and 4 patients with penile malformations other than hypospadias. Immunofluorescence staining of sheets was performed with anti-HLA-DR-FITC and anti-CD207/Langerin-A594 antibodies. Skin sections from 11 patients without penile malformation and 11 patients with hypospadias were stained for Langerin. Frequencies as well as morphology and distribution of epidermal and dermal LCs on sheets and sections were microscopically evaluated. Cell counts were compared by unpaired t-tests.ResultsThere was no difference in frequency of epidermal LCs, Neither on sheets (873 ± 61 vs. 940 ± 84LCs/mm2, p = 0.522) nor on sections (32 ± 3 vs. 30 ± 2LCs/mm2, p = 0.697). Likewise, the frequency of dermal LCs (5,9 ± 0,9 vs. 7.5 ± 1.3LCs/mm2, p = 0.329) was comparable between patients with hypospadias and without penile malformation. No differences became apparent in subgroup analyses, comparing distal to proximal hypospadias (p = 0.949), younger and older boys (p = 0.818) or considering topical dihydrotestosterone treatment prior to surgery (p = 0.08). The morphology of the LCs was not different comparing hypospadias patients with boys without penile malformations.ConclusionsLCs are present in similar frequencies and with a comparable morphology and distribution in patients with hypospadias as compared to children without penile malformations. This suggests that patients with hypospadias are not different from patients with normal penile development considering this particular compartment of their skin immunity.

Highlights

  • Hypospadias are among the most common genital malformations

  • Sheets Interpretable staining without signs of inflammation could be achieved in samples from 12 patients (92.3% of all included patients) without penile malformations, 14 (87.5%) with distal hypospadias, 7 (70%) with proximal hypospadias, one with buried penis (50%) and one with epispadias (50%) translating into a total of 81.4% of all epidermal sheets prepared being amenable for analysis

  • The mean frequency of epidermal Human Leucocyte Antigen (HLA)-DR/CD207 double positive cells per mm2 accounted to 873.4 ± 61.6 in patients with hypospadias (n = 21) as compared to 940.2 ± 84.2 in patients without penile malformation (n = 12, p = 0.522, t-test)

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Summary

Introduction

Hypospadias are among the most common genital malformations. The migration of LC precursors to skin coincides with the embryonic period of hypospadias development and genetic alterations leading to the formation of hypospadias impact the development of ectodermally derived tissues. We hypothesized that this might be associated with a difference in frequency or morphology of epidermal and dermal LCs in hypospadias patients. The events related to the formation of hypospadias happen in very early phases of the genital tubercle outgrow starting in gestational week 8; differentiation of the urethral epithelium is determined by mesenchymal signaling [2]. Thereby, the organogenesis of the urethra is defined and prepuce morphogenesis and surface epithelia of ectodermal origin are influenced [3, 4].

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