Cryoprotective Effect of Pentoxifylline on Spermatogonial Stem Cell During Transplantation into Azoospermic Torsion Mouse Model

Malekzadeh, Mehrnoush; Takzaree, Nasrin; Toolee, Heidar; Kazemzadeh, Shokoofeh; Khanmohammadi, Nasrin; Solhjoo, Somayeh; Sadeghiani, Ghazaleh; Shabani, Maryam; Rastegar, Tayebeh

doi:10.1007/s43032-021-00729-6

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…The high expression for these three markers (PLZF, Thy-1 and α-6 integrin) in SSCs indicated the primary phases of the evolvement of the spermatogenic lineage in isolated SSCs whose differentiation process had not yet initiated and confirmed that SSCs collected after digestion enzymatic were in the undifferentiated stage. The high expression of SSC identification markers in this study was consistent with other studies [ 35 – 37 ].…”

Section: Discussionsupporting

confidence: 93%

“…Increased expression of Stra8 and SCP3 was considerable in the freeze + Mel group compared to the freeze group. Malekzadeh et al found that adding pentoxifylline to the freezing medium improved the recovery of post-thaw SSCs and increased the expression of proliferation (ID4 and Ddx4) and differentiation (SCP3 and C-Kit) proteins compared to frozen–thawed SSCs in the basic freezing medium after transplantation into azoospermic mice [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

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Melatonin in cryopreservation media improves transplantation efficiency of frozen–thawed spermatogonial stem cells into testes of azoospermic mice

et al. 2022

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Background Cryostorage of spermatogonial stem cells (SSCs) is an appropriate procedure for long-term storage of SSCs for fertility preservation. However, it causes damage to cellular structures through overproduction of ROS and oxidative stress. In this study, we examined the protective effect of melatonin as a potent antioxidant in the basic freezing medium to establish an optimal cryopreservation method for SSCs. Methods SSCs were obtained from the testes of neonatal male mice aged 3–6 days. Then, 100 μM melatonin was added to the basic freezing medium containing DMSO for cryopreservation of SSCs. Viability, apoptosis-related markers (BAX and BCL2), and intracellular ROS generation level were measured in frozen–thawed SSCs before transplantation using the MTT assay, immunocytochemistry, and flow cytometry, respectively. In addition, Western blotting and immunofluorescence were used to evaluate the expression of proliferation (PLZF and GFRα1) and differentiation (Stra8 and SCP3) proteins in frozen–thawed SSCs after transplantation into recipient testes. Results The data showed that adding melatonin to the cryopreservation medium markedly increased the viability and reduced intracellular ROS generation and apoptosis (by decreasing BAX and increasing BCL2) in the frozen–thawed SSCs (p < 0.05). The expression levels of proliferation (PLZF and GFRα1) and differentiation (Stra8 and SCP3) proteins and resumption of spermatogenesis from frozen–thawed SSCs followed the same pattern after transplantation. Conclusions The results of this study revealed that adding melatonin as an antioxidant to the cryopreservation medium containing DMSO could be a promising strategy for cryopreservation of SSCs to maintain fertility in prepubertal male children who suffer from cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Melatonin in cryopreservation media improves transplantation efficiency of frozen–thawed spermatogonial stem cells into testes of azoospermic mice

et al. 2022

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“…However, Schramm et al reported that the maximum PTX concentration in seminal plasma was only 75 ng/ml (0.3 μM) ( Schramm and Hinze, 1980 ). Recent two in vitro studies demonstrated the protective impact of PTX on spermatogenesis in mice models with both concentration levels higher than 0.3 μM ( Dhulqarnain et al, 2021 ; Malekzadeh et al, 2021 ). 3) Increased blood perfusion and reduced blood viscosity in testes and epididymis: Pozor and his colleagues confirmed that PTX-treated stallions had significantly higher total arterial blood flow rate than controls, delaying the seasonal decrease of testicular perfusion, without sperm quality and total sperm volume improved ( Pozor et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Poor Sperm Quality and Erectile Dysfunction With Oral Pentoxifylline: A Systematic Review

Lü

Zhang

et al. 2022

Front. Pharmacol.

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Background: Pentoxifylline (PTX) is a member of methylxanthine chemicals and a type of non-selective phosphodiesterase-5 inhibitors, which has been used in male infertility treatment to improve sperm quality and erectile dysfunction (ED) treatment. Mutually tight associations existed between ED and male infertility. Using PTX might kill two birds with one stone by improving sperm quality and erectile function in infertile men with ED.Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched by October 2021. Based on available evidence from observational studies and randomized-controlled trials (RCTs), we conducted a systematic review to summarize the efficacy and safety of PTX in treating ED and male infertility. The protocol of the article was registered and updated in PROSPERO (CRD42021291396).Results: From 202 records, eight studies (7 RCTs) evaluating the role of PTX in ED and three studies (2 RCTs) assessing the efficacy of PTX in male infertility were included in the systematic review. Three studies (100.00%) and two studies (100.00%) reported the beneficial role of PTX in improving sperm progressive motility and normal sperm morphology rate, respectively. In contrast, only one study (33.33%) indicated the favorable role of PTX in enhancing sperm concentration. As for ED, three (60.00%) studies supported the treatment role of PTX alone in ED, and two studies (66.67%) favored the combination use of PTX and selective PDE5Is compared with selective PDE5Is alone. Safety analysis showed that PTX was a well-tolerated drug in ED and male infertility treatment.Conclusion: Given the association between ED and male infertility and satisfying findings from available evidence, PTX administration for the simultaneous treatment of poor sperm quality and mild ED in infertile men will highly enhance the treatment compliance. However, the finding should be treated carefully until validated by further studies.

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“…This is in agreement with results showing that cryopreservation of testicular tissue by slow-freezing in 5% DMSO does not seem to affect the long-term culture of human testicular cells with regard to the presence of germ cell and somatic cell populations ( 32 ). Further optimization and possible addition of novel cryoprotectants, such as the antioxidant pentoxifylline ( 33 ) to the freezing medium may further improve the preservation of human SSC viability. Our research group cryopreserved testicular tissues obtained from orchiectomies of two adult patients with prostate cancer using various protocols in a pilot study.…”

Section: Cryopreservationmentioning

confidence: 99%

Spermatogonial Stem Cell-Based Therapies: Taking Preclinical Research to the Next Level

et al. 2022

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Fertility preservation via biobanking of testicular tissue retrieved from testicular biopsies is now generally recommended for boys who need to undergo gonadotoxic treatment prior to the onset of puberty, as a source of spermatogonial stem cells (SSCs). SSCs have the potential of forming spermatids and may be used for therapeutic fertility approaches later in life. Although in the past 30 years many milestones have been reached to work towards SSC-based fertility restoration therapies, including transplantation of SSCs, grafting of testicular tissue and various in vitro and ex vivo spermatogenesis approaches, unfortunately, all these fertility therapies are still in a preclinical phase and not yet available for patients who have become infertile because of their treatment during childhood. Therefore, it is now time to take the preclinical research towards SSC-based therapy to the next level to resolve major issues that impede clinical implementation. This review gives an outline of the state of the art of the effectiveness and safety of fertility preservation and SSC-based therapies and addresses the hurdles that need to be taken for optimal progression towards actual clinical implementation of safe and effective SSC-based fertility treatments in the near future.

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Cryoprotective Effect of Pentoxifylline on Spermatogonial Stem Cell During Transplantation into Azoospermic Torsion Mouse Model

Cited by 7 publications

References 37 publications

Melatonin in cryopreservation media improves transplantation efficiency of frozen–thawed spermatogonial stem cells into testes of azoospermic mice

Melatonin in cryopreservation media improves transplantation efficiency of frozen–thawed spermatogonial stem cells into testes of azoospermic mice

Treatment of Poor Sperm Quality and Erectile Dysfunction With Oral Pentoxifylline: A Systematic Review

Spermatogonial Stem Cell-Based Therapies: Taking Preclinical Research to the Next Level

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