title: 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: BACKGROUND
  Testicular morphology and immunohistochemical studies have never been reported in genetically documented adult patients with 5 alpha-reductase type 2 deficiency (5α-R2 deficiency).
  
  
  METHODS
  We 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.
  
  
  CONCLUSIONS
  Intratesticular 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.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Vija
authors.forename: Sophie
authors.initials: S
authors.lastname: Ferlicot
authors.forename: Diana
authors.initials: D
authors.lastname: Paun
authors.forename: Hélène
authors.initials: H
authors.lastname: Bry-Gauillard
authors.forename: Gabriela
authors.initials: G
authors.lastname: Berdan
authors.forename: Issam
authors.initials: I
authors.lastname: Abd-Alsamad
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
authors.affiliation: Faculté de Médecine Paris-Sud, Univ Paris-Sud, UMR-S693, Le Kremlin-Bicêtre F-94276, France. jacques.young@bct.aphp.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D013196:Dihydrotestosterone / Q000378:metabolism; D005298:Fertility; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D011627:Puberty / Q000502:physiology*; D011944:Receptors, Androgen / Q000378:metabolism; D012671:Seminiferous Tubules / Q000378:metabolism / Q000473:pathology*; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology*; D013737:Testis / Q000378:metabolism / Q000473:pathology*; D013739:Testosterone / Q000378:metabolism
chemical_list: C410798:AR protein, human; D008565:Membrane Proteins; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human