Status of the executioner step of apoptosis in human with normal spermatogenesis and azoospermia.
OBJECTIVE
To localize the different proteins involved in the executioner step of apoptosis in the human testicular tissue: effector caspases (3, 6, and 7), caspase inhibitors called inhibitor of apoptosis proteins (IAPs, such as XIAP), and IAP inhibitors such as Smac/DIABLO and to investigate XIAP and Smac expression and activation of caspase-3 in azoospermia.


METHODS
Retrospective study.


METHODS
The Biology of Reproduction Center of Poissy and Inserm U407, France.


METHODS
Twenty-five patients diagnosed as azoospermic and 4 patients with normal testicular histology.


METHODS
Testicular biopsies for histopathological assessment.


METHODS
Localization of proteins by immunohistochemistry.


RESULTS
Effector caspase-7 seemed to be absent from normal human testes, whereas procaspase-3 and procaspase-6 were detected in both somatic and germ cells. XIAP was mainly expressed in Sertoli cells, whereas its inhibitor Smac was detected in pachytene spermatocytes. On the other hand, although few apoptotic germ cells were detected in biopsies from patients with obstructive azoospermia, increased levels of apoptotic germ cells were detected in spermatogenetic arrest. This increase in apoptotic germ cells was associated with increased levels of active caspase-3 in patients with spermatogenetic arrest, whereas the expression of XIAP and Smac/DIABLO was at similar levels in all groups.


CONCLUSIONS
Active caspase-3 might be important in the apoptotic process observed in spermatogenetic arrest.
Bozec
Aline
A
Faculté de Médecine Lyon Sud, Inserm, U407, Oullins, Université de Lyon, Lyon, Université Lyon1, France.
Amara
Souheila
S
Guarmit
Basma
B
Selva
Jacqueline
J
Albert
Martine
M
Rollet
Jacques
J
El Sirkasi
Mohamed
M
Vialard
Francois
F
Bailly
Marc
M
Benahmed
Mohamed
M
Mauduit
Claire
C
D000328:Adult; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis* / Q000235:genetics; D053713:Azoospermia / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D053148:Caspase 3 / Q000032:analysis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008297:Male; D024101:Mitochondrial Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D012708:Sertoli Cells / Q000737:chemistry / Q000473:pathology; D013091:Spermatogenesis; D013094:Spermatozoa / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D013737:Testis / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000032:analysis; D055815:Young Adult
D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C505407:CASP3 protein, human; D053148:Caspase 3