In situ end-labeling of human testicular tissue demonstrates increased apoptosis in conditions of abnormal spermatogenesis

Lin, Weigan; Lamb, Dolores J.; Lipshultz, Larry I.; Kim, Edward D.

doi:10.1016/s0015-0282(97)00372-5

Cited by 112 publications

(48 citation statements)

References 20 publications

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“…However, sometimes the adverse conditions are not overcome and this equilibrium is not reached. Increased rates of apoptosis have already been described in cases of azoospermia [17,18]. However, the apoptotic mechanisms involved are still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Caspase signalling pathways in human spermatogenesis

Almeida

Correia

Rocha

et al. 2013

J Assist Reprod Genet

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Purpose Little is known about the apoptotic mechanisms involved in abnormal spermatogenesis. In order to describe the significance of apoptosis in azoospermia, testicular tissue from abnormal spermatogenesis was analysed. Methods Testicular treatment biopsies were obtained from 27 men. Five presented oligozoospermia, 9 obstructive azoospermia (4 congenital bilateral absence of the vas deferens; 5 secondary azoospermia) and 13 nonobstructive azoospermia (5 hypospermatogenis; 3 maturation arrest; 5 Sertoli-cell-only syndrome). Immunohistochemical staining was performed for active caspases-3, −8 and −9. The presence of active caspases in Sertoli cells and germ cells was analyzed using stereological tools. Results Increased active caspase-3 was found in Sertoli-cellonly syndrome. No significant differences were found in maturation arrest. In hypospermatogenesis, primary spermatocytes were the germ cells with higher active caspases. Oligozoospermia and secondary obstruction showed significant differences among germ cells for the presence of all active caspases. In oligozoospermia, spermatogonia presented significant increased active caspase-9 in relation to active caspase-8. In primary obstruction and hypospermatogenesis, germ cells presented significant increased active caspases-3 and −9. Conclusions Results suggest that increased active caspase-3 might be involved in Sertoli-cell-only syndrome etiology. In cases of hypospermatogenesis, intrinsic lesions at the meiotic stage seem to be related to the pathology. In secondary obstruction apoptosis is suggested to be initiated due to extrinsic and intrinsic lesions, whereas in primary obstruction only the intrinsic apoptotic pathway seems to be present. Finally, in oligozoospermic patients spermatogonia death by mitochondrial damage additionally to meiosis malfunctioning, might be on the origin of the decreased sperm output.

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Section: Discussionmentioning

confidence: 99%

Caspase signalling pathways in human spermatogenesis

Almeida

Correia

Rocha

et al. 2013

J Assist Reprod Genet

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“…It also plays an essential role in gamete maturation and embryogenesis, contributing to appropriate formation of various organs and structures. In fact, many studies in animal models have demonstrated that apoptosis is the underlying mechanism of germ cell death during normal spermatogenesis [2], which has also been reported in humans [3].On the other hand, deregulations of this biological process, which is closely associated with male infertility, have been found, and both men with azoospermia and men with severe oligozoospermia have an increased frequency of apoptotic germ cells in their testicular tissues compared with patients having normal spermatogenesis [2,4,5]. In addition, a certain degree of spontaneous apoptosis and relatively high rates of apoptosis have been detected using an in situ end-labelling (TUNEL) assay in testicular biopsies of infertile patients with testicular insufficiency [6,7].…”

mentioning

confidence: 86%

“…On the other hand, deregulations of this biological process, which is closely associated with male infertility, have been found, and both men with azoospermia and men with severe oligozoospermia have an increased frequency of apoptotic germ cells in their testicular tissues compared with patients having normal spermatogenesis [2,4,5]. In addition, a certain degree of spontaneous apoptosis and relatively high rates of apoptosis have been detected using an in situ end-labelling (TUNEL) assay in testicular biopsies of infertile patients with testicular insufficiency [6,7].…”

mentioning

confidence: 99%

Relationship between Caspase Activity and Apoptotic Markers in Human Sperm in Response to Hydrogen Peroxide and Progesterone

et al. 2009

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Abstract. Apoptosis plays an essential role in normal spermatogenesis, but deregulations of this biological process, which is closely associated with male infertility, have been found. Whereas calcium homeostasis is a key regulator of cell survival, sustained elevation of intracellular calcium plays a role in apoptosis. The aim of this research was to determine the role of two different calcium mobilizing agents, hydrogen peroxide (H2O2) and the physiological agonist progesterone, on the apoptosis process of human ejaculated spermatozoa. Translocation of membrane phosphatidylserine was examined with an annexin V binding assay, DNA damage was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL assay) and caspase-3 activity was assessed using a fluorometric assay. After incubation of spermatozoa for 1 h with either 10 μM H2O2 or 20 μM of progesterone, there was a significant increase in both caspase-3 activity and the percentage of annexin V-positive cells. Similarly, the TUNEL results were significantly higher 1 h after incubation with either 10 μM H2O2 or 20 μM of progesterone. In fact, progesterone-treated cells showed a three-fold increase (from 17.6 to 52.9%) of TUNEL-positive cells compared to untreated cells, while H2O2-treated cells exhibited a two-fold increase (from 17.6 to 37.9%). In sum, our results suggest that spermatozoa treated with calcium mobilizing agents, such as H2O2 and progesterone, seem to undergo an apoptosis process that is dependent on caspase-3 activation. Key words: Apoptosis, Caspases, Phosphatidylserine exposure, Spermatozoa, TUNEL (J. Reprod. Dev. 55: [615][616][617][618][619][620][621] 2009) poptosis is a distinctive form of cell death characterized by a series of morphological and biochemical changes that plays a critical role in many physiological processes such as development, tissue homeostasis, inflammatory responses and disease [1]. It also plays an essential role in gamete maturation and embryogenesis, contributing to appropriate formation of various organs and structures. In fact, many studies in animal models have demonstrated that apoptosis is the underlying mechanism of germ cell death during normal spermatogenesis [2], which has also been reported in humans [3].On the other hand, deregulations of this biological process, which is closely associated with male infertility, have been found, and both men with azoospermia and men with severe oligozoospermia have an increased frequency of apoptotic germ cells in their testicular tissues compared with patients having normal spermatogenesis [2,4,5]. In addition, a certain degree of spontaneous apoptosis and relatively high rates of apoptosis have been detected using an in situ end-labelling (TUNEL) assay in testicular biopsies of infertile patients with testicular insufficiency [6,7]. Similarly, disturbance of cell membrane symmetry with translocation of phospatidylserine residues to the outer layer of the plasma membrane has been observed in germ cells from patients with complete spermi...

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“…Apoptosis is an active phenomenon resulting in cell death, and is crucial in maintaining the integrity of an organ [3]. Apoptosis is a common phenomenon during spermatogenesis, and its dysregulation has been associated with male infertility.…”

Section: Introductionmentioning

confidence: 99%

Caspase-3 and VEGF immunopositivity in seminiferous tubule germ cells in cases of obstructive and non-obstructive azoospermia in smokers versus non-smokers

Kılıç¹,

Lortlar²,

Bardakçı³

et al. 2008

J Assist Reprod Genet

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Purpose To investigate immunostaining pattern of caspase-3, an apoptosis marker, and vascular endothelial growth factor (VEGF), an hypoxia marker in testis biopsy specimens collected either from smoking or non-smoking patients with azoospermia. Methods Testis biopsy specimens were obtained from thirty seven non-smoker and thirty eight smoker patients. Using immunochemistry technique, caspase-3 and VEGF were evaluated in all intratubular spermatogenic and interstitial Leydig cells.Result(s) Caspase-3 expression was significantly increased in germ cells in maturation arrest specimens in smoker azoospermic patients. No statistically significant difference was present between smokers and non-smokers for caspase-3 expression in Sertoli cell. However, the VEGF immunopositive Leydig cells were statistically higher in smokers. There were no differences between groups in terms of germ cell immunopositivity. Conclusion Our results support the hypothesis that increased apoptosis contributes significantly to impaired spermatogenesis. We conjecture that germ cell apoptosis

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In situ end-labeling of human testicular tissue demonstrates increased apoptosis in conditions of abnormal spermatogenesis

Cited by 112 publications

References 20 publications

Caspase signalling pathways in human spermatogenesis

Caspase signalling pathways in human spermatogenesis

Relationship between Caspase Activity and Apoptotic Markers in Human Sperm in Response to Hydrogen Peroxide and Progesterone

Caspase-3 and VEGF immunopositivity in seminiferous tubule germ cells in cases of obstructive and non-obstructive azoospermia in smokers versus non-smokers

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