Background: In Androgen insensitivity syndrome (AIS) is a hereditary disease in which AR mutations in 46,XY patients present with partial (PAIS) or complete (CAIS) defects in virilisation.
Objective and hypotheses: The aim was to analyze the effect of lack of androgen action in germ cell (GC) health and survival along postnatal development, previous to Sertoli cell (SC) pubertal maturation.
Method: The histological features and quantity of GC in testes of AIS patients were compared to controls (C). Fourteen gonads of 10 AIS patients (median age 9.55, range 1.823 y) were studied. Three prepubetal (PP) and 4 pubertal (PUB) were CAIS and 3 PP were PAIS. Clinical diagnosis was confirmed by hormonal and molecular studies. Testes of C were collected at necropsy or biopsy from 11 PP and 4 PUB patients without endocrine disorders. A written consent was obtained. The Ethical Committee approved the study. GCs were identified using anti MAGE-A4 antibody.
Results: PP AIS testes showed abundant gonocytes, huge GCs, calcifications, thickened basal membrane and/or fibrous interstitium. In PUB AIS testes signs of dysgenesis as Leydig cell hyperplasia, PP-like seminiferous cords with vacuolated SCs, scarce or none GCs and absence of meiotic spermatocytes were found. PPC and PUBC showed normal testicular parenchyma according to age. MAGE-A4 expression correlates with the presence of GC. AIS testes show a drastically loss of GC after 4.4 y (r=0.558, P=0.038). As the staining decreases, foci of positive cords were found. No difference between PAIS and CAIS was observed. In contrast, C shows an increase of MAGE-A4 expression as a function of age (r=0.595, P=0.019) and the staining pattern was homogeneous.
Conclusion: Disturbed androgen action delayed the GC maturation rate during fetal and early postnatal life. Our results demonstrated that in an androgen deprived niche, GC number rapidly declined during childhood.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology