Involvement of the Fas–Fas ligand system and active caspase-3 in abnormal apoptosis in human testes with maturation arrest and Sertoli cell–only syndrome

Abstract

To provide evidence that the Fas-mediated apoptotic process may participate in developing hypospermatogenesis, such as maturation arrest (MA) and Sertoli cell-only syndrome (SCO). Prospective clinical and descriptive study. Hospital-based infertility research laboratory and university laboratory. Twenty-two testicular biopsy specimens were obtained for routine clinical purposes from 12 men with nonobstructive azoospermia and from 10 men with obstructive azoospermia. In situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used for detection of apoptosis. Reverse transcription-polymerase chain reaction and immunohistochemical analyses were used for detection of testicular expressions of Fas, Fas ligand (FasL), and caspase-3. Apoptotic indices and testicular expressions of apoptosis regulators. Increased apoptosis of germ cells and Sertoli cells was observed in MA and SCO compared with normal spermatogenesis. In testes with MA, increased immunostaining for FasL was observed in the Sertoli cells and Leydig cells, while intense immunostaining of Fas was observed in primary degenerating spermatocytes. Active caspase-3 immunostaining was detected in the cytoplasm of both Sertoli cells and germ cells. In cases of SCO, expression of Fas, FasL, and active caspase-3 was detected both in Sertoli cells and in hyperplastic interstitial cells. The current study demonstrates that the expression of FasL is upregulated in the testes of patients with SCO and MA, which suggests that it may be associated with apoptotic elimination or altered maturation of Fas-expressing germ cells through the activation of caspase-3.