Testicular histological and immunohistochemical aspects in a post-pubertal patient with 5 alpha-reductase type 2 deficiency: case report and review of the literature in a perspective of evaluation of potential fertility of these patients

Abstract

BackgroundTesticular morphology and immunohistochemical studies have never been reported in genetically documented adult patients with 5 alpha-reductase type 2 deficiency (5α-R2 deficiency).Case presentationWe describe the testicular histopathology of a 17-year-old XY subject with 5α-R2 deficiency caused by the recurrent homozygous Gly115Asp loss of function mutation of the SRD5A2 gene.We also performed an immunohistochemical analysis in order to further study the relationship between seminiferous tubules structure, Sertoli cell differentiation and androgenic signaling impairment in this case. We thus evaluated the testicular expression of the anti-Müllerian hormone (AMH), androgen receptor (AR) and 3β-hydroxysteroid dehydrogenase (3βHSD). Histological analysis revealed a heterogeneous aspect with a majority (92%) of seminiferous tubules (ST) presenting a mature aspect but containing only Sertoli cells and devoid of germ cells and spermatogenesis. Focal areas of immature ST (8%) were also found. Testicular AR and 3βHSD expression were detected in adult male control, 5α-R2 deficiency and CAIS subjects. However, AMH expression was heterogeneous (detectable only in few AR negative prepubertal ST, but otherwise repressed) in the 5α-R2 deficiency, conversely to normal adult testis in which AMH was uniformly repressed and to an adult CAIS testis in which AMH was uniformly and strongly expressed.ConclusionIntratesticular testosterone can repress AMH by itself, independently of its metabolism into dihydrotestosterone. We also compare our results to the few post pubertal cases of 5α-R2 deficiency with available histological testicular description, reported in the literature. We will discuss these histological findings, in the more general context of evaluating the fertility potential of these patients if they were raised as males and were azoospermic.

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature

“…Case Report M-A Burckhardt and others Histology of HSD3B2 deficiency 173:5 K8 Table 4 (8,9,12,13,14,16,23,24,25,26,27,28,29,30,31,32,33,34,35,36). For spermatogenesis and thus fertility, the few data available suggest that it varies between different androgen biosynthetic defects as well as between individuals carrying defects in the same gene.…”

Immunophenotyping of Rabbit Testicular Germ and Sertoli Cells Across Maturational Stages

“…21,54,55,57 AMH is absent in normal adult testes but can be reexpressed in pathological conditions such as testicular atrophy, androgen insensitive syndromes, 5α-reductase type 2 deficiency, and SC tumors. 20,27,58 As far as the rabbit species is concerned, previous studies have demonstrated the immunohistochemical expression of AMH in fetal testes. 26,55 In the present study, AMH was detected in neonatal and prepubertal testes, its expression decreased with age, and it was totally absent in adult testes.…”

Importance of Serum Testicular Protein Hormone Measurement in the Assessment of Disorders of Sex Development

“…Because intratesticular androgen concentration and androgen receptor expression are normal and FSH is not elevated, serum AMH is not increased in these patients [Stuchi-Perez et al, 2005;Vija et al, 2014].…”