Reversion of the differentiated phenotype and maturation block in Sertoli cells in pathological human testis.
To study the relationship between abnormal Sertoli cell differentiation and spermatogenic impairment, we examined the expression of Sertoli cell markers normally lost at puberty, cytokeratin 18 (CK18), anti-Müllerian hormone (AMH) and M2A antigen, in three children (aged 1-2 years), 50 adults (aged 19-45 years) with obstructive or non-obstructive azoospermia or oligozoospermia, and six patients (aged 1-18 years) with 5 alpha-reductase deficiency. There was CK18 and/or AMH expression, but never M2A antigen expression, associated with spermatogonial arrest or Sertoli cell-only (SCO) syndrome in infertile men. Loss of M2A antigen suggests the transition of Sertoli cells to an adult phenotype, while CK18 and/or AMH expression may be a manifestation of de-differentiation of Sertoli cells. In 5 alpha-reductase deficiency, there was a sequential loss of CK18, M2A antigen and AMH around puberty, associated with partial spermatogenesis. The persistence of immature Sertoli cells expressing M2A antigen was associated with prepubertal seminiferous cords and SCO syndrome. Therefore, 5 alpha-reductase deficiency may prevent the maturation of Sertoli cells, resulting in impairment of spermatogenesis, and loss of M2A antigen expression coincides with a critical step in the Sertoli cell maturation. High follicle stimulating hormone concentrations due to failure of normal Sertoli cell differentiation indicate a normal development pattern of the hypothalamic-pituitary-gonadal axis.
Steger
K
K
Institute of Anatomy and Cell Biology, University of Halle, Saale, Germany.
Rey
R
R
Louis
F
F
Kliesch
S
S
Behre
H M
HM
Nieschlag
E
E
Hoepffner
W
W
Bailey
D
D
Marks
A
A
Bergmann
M
M
D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone; D000951:Antigens, Neoplasm / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D042944:Cholestenone 5 alpha-Reductase; D002828:Choristoma / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D007223:Infant; D007248:Infertility, Male / Q000378:metabolism / Q000473:pathology*; D007633:Keratins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000378:metabolism / Q000473:pathology; D010088:Oxidoreductases / Q000172:deficiency; D010641:Phenotype; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology*; D013577:Syndrome; D013735:Testicular Hormones / Q000378:metabolism; D013737:Testis / Q000473:pathology*
D000951:Antigens, Neoplasm; D006023:Glycoproteins; D006131:Growth Inhibitors; D013735:Testicular Hormones; C031192:oncofetal antigens; D007633:Keratins; D054304:Anti-Mullerian Hormone; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase