Reduced sperm yield from testicular biopsies of vasectomized men is due to increased apoptosis

O’Neill, D.A.; McVicar, Carmel; McClure, Neil; Maxwell, Perry; Cooke, Inez; Pogue, Katherine M.; Lewis, Sheena

doi:10.1016/j.fertnstert.2006.11.018

Cited by 31 publications

(17 citation statements)

References 62 publications

(56 reference statements)

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“…Therefore, vasectomized men undergoing TESE were used as controls, as Dohle et al (1998) confirmed normal maturation according to the Johnsen score (Johnsen, 1970) in patients with OA, normal testicular volume and serum FSH, even if PESA failed. Although the maturation process and number of Sertoli cells appear to be normal, sperm counts are reported to be reduced in vasectomized men (McVicar et al, 2005;O'Neill et al, 2007). However, the cytological diagnosis of complete spermatogenesis in three vasectomized men was confirmed by histology.…”

Section: Discussionmentioning

confidence: 85%

Cytological evaluation of spermatogenesis: a novel and simple diagnostic method to assess spermatogenesis in non-obstructive azoospermia using testicular sperm extraction specimens

et al. 2015

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SUMMARYMost of the non-obstructive azoospermia (NOA)-patients have only focal spermatogenesis which results in insufficient numbers of spermatozoa to reach the ejaculate. In 50% of these NOA-patients testicular sperm extraction (TESE) is successful and intracytoplasmic sperm injection (ICSI) is pursued. We studied whether (i) spermatogenesis can be evaluated by defining the ratios between Sertoli cells, pachytene spermatocytes and spermatozoa in a testicular cell suspension, and (ii) these ratios are associated with the outcome of fertility treatment. A retrospective cohort study was conducted between June 2007 and August 2012. In this period, 441 consecutive ICSI-TESE cycles were performed in 212 couples. For each TESE biopsy, the ratios between Sertoli cells, pachytene spermatocytes and spermatozoa were calculated. A control population of 32 vasectomized men was used to define cut-off values for complete spermatogenesis. Based on the pachytene to sperm ratio (P/Sp) and number of spermatozoa per 100 Sertoli cells (#Sp/ 100SC) groups were defined as complete spermatogenesis, hypospermatogenesis and partial maturation arrest (MA). Validation of the cytological diagnoses was performed by comparing the results of cytology to the histological evaluation of spermatogenesis in 40 cases. In 92.5%, a perfect match was observed and in the three remaining cases cytology corresponded well with the results of TESE. Couples with complete spermatogenesis have a higher ongoing pregnancy rate after the first treatment cycle compared to couples with hypospermatogenesis (34 vs. 16%; p = 0.02) and partial MA (34 vs. 19%; p = 0.11). In conclusion, pachytene spermatocytes, spermatozoa and Sertoli cells can be easily identified and counted in a cell suspension and their ratios can be successfully used to diagnose the level of spermatogenic impairment. This pilot study indicates that once successful spermatozoa retrieval is achieved, treatment outcome declines when spermatogenesis is impaired in NOA. The predictive value of cytological evaluation of spermatogenesis has to be established in a future prospective trial.

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Section: Discussionmentioning

confidence: 85%

Cytological evaluation of spermatogenesis: a novel and simple diagnostic method to assess spermatogenesis in non-obstructive azoospermia using testicular sperm extraction specimens

et al. 2015

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“…Accumulation of sperm in the epididymis following vasectomy may lead to deregulation of ROS generation, causing oxidative stress and epididymal dysfunction [McVicar et al 2005], and lead to functional and structural damage in the sperm [Suresh et al 2010]. Similarly, the observed increase in apoptotic cells in testis of vasectomized animals could be ROS mediated [Wang et al 2012] and thus reduce sperm yields during biopsy after vasectomy with increasing years [O'Neill et al 2007]. Consequently, TUNEL positive cells were more abundant in short-term as compared to long-term post vasectomy indicating reduced spermatogenesis in the latter.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, TUNEL positive cells were more abundant in short-term as compared to long-term post vasectomy indicating reduced spermatogenesis in the latter. Several pathway apoptotic mediators after vasectomy include p53-Bax [Shiraishi et al 2001], Fas-FasL mediated [O'Neill et al 2007] and survivin downregulation and Bax over expression [Al-Maghrebi et al 2011]. These will be interesting aspects to explore in vasectomized subjects.…”

Section: Discussionmentioning

confidence: 99%

Long-term study of vasectomy inMacaca radiata– histological and ultrasonographic analysis of testis and duct system

Prakash

Krishnaswamy

2014

Systems Biology in Reproductive Medicine

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This study was aimed to investigate the long-term effect of vasectomy using the bonnet monkey (Macaca radiata) as a primate animal model. Animals weighing around 6 to 8 kg were randomly chosen for bilateral, unilateral vasectomy and sham-control. The postoperative periods of six months and two years were considered as short and long-term, respectively. Sperm were collected and subjected to analysis before euthanasia. The testes and epididymides were excised from euthanized animals then embedded in paraffin. Normal histological changes were observed in sham-operated animals and short-term contralateral testes. In contrast, marked alterations were observed in the testes and epididymides of both short and long-term groups. Seminiferous epithelium was thinned out showing marked depletion of germ cells in long-term; only a thin layer of Sertoli cells, spermatogonia, and fewer spermatocytes were seen. Exfoliation of germ cells and the occurrence of multinucleated giant cells were common features in these tubules. The epididymal tubular lumens were greatly dilated with accumulated spermatozoa in short and long-term animals; significant defects were observed in the epithelium of the long-term animals. Microscopic spermatic granulomas were noticed in epididymides and the vas deferens. Large granulomas were seen in long-term vasectomized monkeys, frequently compressing the surrounding structures. These granulomas could be visualized in ultrasound, however, only at the late stage of its occurrence. Sperm collected from the unilateral vasectomized animals showed a poor motility score in the capillary mucus penetration test (CMPT). Results indicate that the changes observed after vasectomy might be due to pressure initially, whereas in the long-term the damage was supplemented by autoimmune attack. With immunoglobulin (IgG) deposition in contra-lateral unoperated testis of unilateral vasectomized animals it also showed degenerative changes and a concomitant drop in sperm quality. Although, granulomatous reactions were observed in the epididymis and vas deferens but testes were spared from such reactions even in the long-term.

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“…We sought to determine a mechanism by which this reduction in sperm yield and pregnancy rate was effected by investigating the incidence of apoptosis in the seminiferous tubules ( Figure 2) [62]. In general, apoptosis plays an important role in the testis [45,69] by eliminating 50-70% of germ cells at different stages of spermatogenesis prior to spermiogenesis [40,9,61].…”

Section: Y I E L D Smentioning

confidence: 99%

“…Sperm DNA fragmentation, an end point marker of apoptosis, increased significantly in vasectomised men compared to fertile men. [62] (provisional acceptance).…”

Section: Y I E L D Smentioning

confidence: 99%

Traitement de l’azoospermie obstructive par injection Intracytoplasmique d’un spermatozoïde

Lewis

2006

Androl.

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Intracytoplasmic sperm injection (ICSI) allows the treatment of virtually every type of male infertility. Unlike in vitro fertilization (IVF), its success does not depend on sperm concentration, motility or morphology and most of the physical barriers to fertilisation are by-passed. Since ICSl does not require strongly motile sperm, its use has now been expanded to incorporate immature sperm from the testes and epididymides. Successful fertilisation, pregnancies and healthy babies have all been reported. However, concerns about the safety of ICSl remain due to its short clinical history and the lack of testing on animal models.Male fertility potential for assisted reproduction by ICSl cannot be measured by conventional parameters. Sperm DNA integrity is increasingly recognised as a more useful indicator. Studies have shown that sperm with higher levels of DNA damage have lower fertilisation rates after IVF and ICSI. Sperm with DNA damage above a certain threshold are associated with a longer time to conceive in otherwise apparently fertile couples and a higher miscarriage rate. DNA damage has been shown to be associated with impaired embryo cleavage. Our group has shown that sperm DNA from testicular sperm is less fragmented than that from epididymal sperm and suggest its preferred use in ICSI.In addition to nuclear (n) DNA we also assessed the quality of mitochondrial (mt) DNA from testicular sperm from men with obstructive azoospermia undergoing ICSI. We observed that couples achieving a pregnancy had both less mtDNA deletions and less nDNA fragmentation. We found inverse relationships between pregnancy and sperm mtDNA deletion numbers, size and nDNA fragmentation. No relationships were observed with fertilisation rates. With this knowledge, we designed an algorithm for the prediction of pregnancy based on the quality of sperm nDNA and mtDNA.Each year 40,000 men have a vasectomy in the UK but every year 2500 request a reversal to begin a second family. For such men, vasectomy reversal has recently been replaced in part by testicular biopsy via fine-needle testicular sperm aspiration (TESA) or percutaneous epididymal sperm aspiration (PESA) performed at an outpatient clinic and subsequently used in ICSI. Since these were previously fertile men it has been assumed that they had 'fertile' sperm. However the assisted conception success rates of these mens partners has not been assessed until recently. We have shown a significant reduction in the clinical pregnancy rates in the partners of men who had had a vasectomy >10yrs previously. There is also evidence to suggest that spermatogenesis is significantly impaired in vasectomised men. Marked decreases in spermatocytes, spermatids and spermatozoa have been observed. We have found this to be associated with concomitant increases in apoptotic markers, such as Fas, FasL and Bax. The quality of the remaining sperm is also compromised. Sperm DNA from vasectomized men shows substantial damage which increases with time after surgery. This new use of ICSI will be d...

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Reduced sperm yield from testicular biopsies of vasectomized men is due to increased apoptosis

Cited by 31 publications

References 62 publications

Cytological evaluation of spermatogenesis: a novel and simple diagnostic method to assess spermatogenesis in non-obstructive azoospermia using testicular sperm extraction specimens

Cytological evaluation of spermatogenesis: a novel and simple diagnostic method to assess spermatogenesis in non-obstructive azoospermia using testicular sperm extraction specimens

Long-term study of vasectomy inMacaca radiata– histological and ultrasonographic analysis of testis and duct system

Traitement de l’azoospermie obstructive par injection Intracytoplasmique d’un spermatozoïde

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