Introduction. The vast majority of the patients with classical Klinefelter syndrome (KS) have azoospermia. However, a low number of spermatozoa may be found in the ejaculates or within the testis in a small proportion of them. The exact mechanism(s) which causes spermatogenesis failure is still unknown. Mechanisms of testicular degeneration in KS have been extensively studied and several hypotheses have been proposed. These include Leydig-cell insufficiency, impaired Sertoli cell function, a dysfunctional communication between Sertoli cells and germ cells, apoptotic mechanism. Apoptosis plays an important role for normal spermatogenesis to occur. LDOC1 gene is a known regulator of the nuclear factor-mediated pathway to apoptosis through inhibition of NF-kappaB. Furthermore, the transcription factor myeloid zinc finger gene 1 (MZF-1) interacts with LDOC1 and enhances LDOC1 activity favoring apoptosis. Aim. On this account, this study was undertaken to evaluate the expression of LDOC1 gene in KS patients. Methods. To accomplish this, LDOC1 mRNA was evaluated by qRT-PCR in blood lymphocytes from 13 KS patients and 13 age-matched controls. Their mean age was 30.9±11.4 (range 21-69) years and 30.4±11.1 (range 21-59) years, respectively. All KS patients had a 47,XXY karyotype, azoospermia and were on testosterone replacement therapy ever since diagnosis. Results. LDOC1 gene expression was higher in 9 KS patients (69.2%) compared to normal controls. Two of them had a gene expression at least four times higher compared to controls. Moreover, 2 of the 9 samples of KS patients showed an expression LDOC1 greater than 1.5 compared to the corresponding normal sample. Conclusion. These findings showed that LDOC1 gene is up-regulated in patients with KS. This overexpression may play a role in the spermatogenesis derangement observed in patients with KS as well as in the inflammatory and immune-related diseases often encountered in these patients. We speculate that LDOC1 gene expression may be regarded as a marker of the apoptotic mechanisms in KS.
GENE EXPRESSION IN MEN WITH KLINEFELTER SYNDROME
RA Condorelli;LA VIGNERA, SANDRO SALVUCCIO MARIA;
2014-01-01
Abstract
Introduction. The vast majority of the patients with classical Klinefelter syndrome (KS) have azoospermia. However, a low number of spermatozoa may be found in the ejaculates or within the testis in a small proportion of them. The exact mechanism(s) which causes spermatogenesis failure is still unknown. Mechanisms of testicular degeneration in KS have been extensively studied and several hypotheses have been proposed. These include Leydig-cell insufficiency, impaired Sertoli cell function, a dysfunctional communication between Sertoli cells and germ cells, apoptotic mechanism. Apoptosis plays an important role for normal spermatogenesis to occur. LDOC1 gene is a known regulator of the nuclear factor-mediated pathway to apoptosis through inhibition of NF-kappaB. Furthermore, the transcription factor myeloid zinc finger gene 1 (MZF-1) interacts with LDOC1 and enhances LDOC1 activity favoring apoptosis. Aim. On this account, this study was undertaken to evaluate the expression of LDOC1 gene in KS patients. Methods. To accomplish this, LDOC1 mRNA was evaluated by qRT-PCR in blood lymphocytes from 13 KS patients and 13 age-matched controls. Their mean age was 30.9±11.4 (range 21-69) years and 30.4±11.1 (range 21-59) years, respectively. All KS patients had a 47,XXY karyotype, azoospermia and were on testosterone replacement therapy ever since diagnosis. Results. LDOC1 gene expression was higher in 9 KS patients (69.2%) compared to normal controls. Two of them had a gene expression at least four times higher compared to controls. Moreover, 2 of the 9 samples of KS patients showed an expression LDOC1 greater than 1.5 compared to the corresponding normal sample. Conclusion. These findings showed that LDOC1 gene is up-regulated in patients with KS. This overexpression may play a role in the spermatogenesis derangement observed in patients with KS as well as in the inflammatory and immune-related diseases often encountered in these patients. We speculate that LDOC1 gene expression may be regarded as a marker of the apoptotic mechanisms in KS.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
