Apoptotic Frequency Is Increased in Spermatogenic Maturation Arrest and Hypospermatogenic States

Lin, Weigan; Lamb, Dolores J.; Wheeler, Thomas M.; Abrams, Jacki; Lipshultz, Larry I.; Kim, Edward D.

doi:10.1016/s0022-5347(01)64130-2

Cited by 55 publications

(44 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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“…However, excessive cell death may result in subsequent impairment of spermatogenic differentiation (Li et al 2011b). Similarly, apoptotic frequency is increased in spermatogenic maturation arrest and hypospermatogenic states of both experimental rodents and human patients (Lin et al 1997). Therefore, multifactorial mechanisms are warranted in pachytene spermatocytes to ensure the maintenance of proper balance of apoptosis upon stress conditions.…”

Section: Role Of Egf In Testicular Ischemia-reperfusion Injurymentioning

confidence: 99%

Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury

Zhang

Zeng

et al. 2013

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Administration of exogenous epidermal growth factor (EGF) improves testicular injury after acute ischemia-reperfusion (IR) stress, but the molecular basis is poorly understood. The role of endogenous EGF in testicular recovery and the underlying intracellular signaling pathways involved were herein investigated. In mice, testicular IR injury significantly enhanced the expression level of endogenous Egf at the very beginning of reperfusion. Expression of EGF receptor (Egfr (ErbB1)) was accordingly upregulated 3 h after reperfusion. Deprivation of majority of circulated EGF by sialoadenectomy aggravated testicular detriment (especially in pachytene spermatocytes), enhanced germ cell apoptosis, and thereafter resulted in impaired meiotic differentiation after IR insult. Mechanistically, endogenous EGF signaling appeared to be indispensable for the proper maintenance of Sertoli germ cells anchoring junction dynamics during the early testicular recovery. We also provided the in vitro evidences in a well-established rat Sertoli germ cell co-cultures model that the pro-survival effect of endogenous EGF on germ cells in response to testicular IR insult is mediated, at least in part, via the phosphatidylinositol 3-kinase/pAkt pathway. Collectively, our results suggest that the augment of endogenous EGF during the early testicular recovery may act on top of an endocrinous cascade orchestrating the intimate interactions between Sertoli cells and germ cells and may operate as indispensable defensive mechanism in response to testicular IR stress. Future studies in this field would shed light on this complicated pathogenesis.

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“…Later in life, apoptosis is involved in the removal of germ cells that are damaged as a result of exposure to environmental toxicants, chemotherapeutic agents, or heat (Wang et al 2007). A role of apoptosis in the etiology of spontaneous male infertility has also been suggested by virtue of the excessively high numbers of apoptotic germ cells observed in the testes of some infertile males (Lin et al 1997). In addition, apoptotic markers including caspase activation and phophotidylserine exteriorization have been discovered in the mature spermatozoa of male infertility patients (Barroso et al 2000, Paasch et al 2004, Almeida et al 2009, Grunewald et al 2009, Aitken & Curry 2011.…”

Section: Apoptosis In the Testesmentioning

confidence: 99%

Apoptosis in the germ line

Aitken¹,

Findlay²,

Hutt³

et al. 2011

Reproduction

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102

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Apoptosis is a critical process for regulating both the size and the quality of the male and female germ lines. In this review, we examine the importance of this process during embryonic development in establishing the pool of spermatogonial stem cells and primordial follicles that will ultimately define male and female fertility. We also consider the importance of apoptosis in controlling the number and quality of germ cells that eventually determine reproductive success. The biochemical details of the apoptotic process as it affects germ cells in the mature gonad still await resolution, as do the stimuli that persuade these cells to commit to a pathway that leads to cell death. Our ability to understand and ultimately control the reproductive potential of male and female mammals depends upon a deeper understanding of these fundamental processes.

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Apoptotic Frequency Is Increased in Spermatogenic Maturation Arrest and Hypospermatogenic States

Abstract: Increased apoptosis in maturation arrest and hypospermatogenesis states compared to normal but obstructed spermatogenesis and Sertoli cell only were observed, indicating a prominent role for this form of programmed cell death in human male infertility.

Cited by 55 publications

References 20 publications

Caspase signalling pathways in human spermatogenesis

Caspase signalling pathways in human spermatogenesis

Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury

Apoptosis in the germ line

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