FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges

Kilcoyne, Karen; Mitchell, Rod

doi:10.1530/rep-18-0533

Cited by 24 publications

(21 citation statements)

References 77 publications

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“…Current strategies to preserve fertility in prepubertal boys involve cryopreservation of testicular material [8,21]. However, the future success of this process to restore fertility later in life is dependent on the preservation of germ cells with stem cell capability of cryopreserved tissues [22]. It is conceivable that some of the surviving (MAGEA4 + /UTF1 − ) germ cells in these patients may retain, or acquire, SSC capabilities following gonadotoxic therapy, as has been demonstrated in mouse models of testicular regeneration and repair following exposure to busulphan, a chemotherapeutic belonging to the highly gonadotoxic group of alkylating agents [23].…”

Section: Discussionmentioning

confidence: 99%

Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer

Tharmalingam

Matilionyte

Wallace

et al. 2020

BMC Med

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Background Clinical studies indicate chemotherapy agents used in childhood cancer treatment regimens may impact future fertility. However, effects of individual agents on prepubertal human testis, necessary to identify later risk, have not been determined. The study aimed to investigate the impact of cisplatin, commonly used in childhood cancer, on immature (foetal and prepubertal) human testicular tissues. Comparison was made with carboplatin, which is used as an alternative to cisplatin in order to reduce toxicity in healthy tissues. Methods We developed an organotypic culture system combined with xenografting to determine the effect of clinically-relevant exposure to platinum-based chemotherapeutics on human testis. Human foetal and prepubertal testicular tissues were cultured and exposed to cisplatin, carboplatin or vehicle for 24 h, followed by 24–240 h in culture or long-term xenografting. Survival, proliferation and apoptosis of prepubertal germ stem cell populations (gonocytes and spermatogonia), critical for sperm production in adulthood, were quantified. Results Cisplatin exposure resulted in a significant reduction in the total number of germ cells (− 44%, p < 0.0001) in human foetal testis, which involved an initial loss of gonocytes followed by a significant reduction in spermatogonia. This coincided with a reduction (− 70%, p < 0.05) in germ cell proliferation. Cisplatin exposure resulted in similar effects on total germ cell number (including spermatogonial stem cells) in prepubertal human testicular tissues, demonstrating direct relevance to childhood cancer patients. Xenografting of cisplatin-exposed human foetal testicular tissue demonstrated that germ cell loss (− 42%, p < 0.01) persisted at 12 weeks. Comparison between exposures to human-relevant concentrations of cisplatin and carboplatin revealed a very similar degree of germ cell loss at 240 h post-exposure. Conclusions This is the first demonstration of direct effects of chemotherapy exposure on germ cell populations in human foetal and prepubertal testis, demonstrating platinum-induced loss of all germ cell populations, and similar effects of cisplatin or carboplatin. Furthermore, these experimental approaches can be used to determine the effects of established and novel cancer therapies on the developing testis that will inform fertility counselling and development of strategies to preserve fertility in children with cancer.

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Section: Discussionmentioning

confidence: 99%

Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer

Tharmalingam

Matilionyte

Wallace

et al. 2020

BMC Med

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“…Future studies should consider strategies to achieve further improvements in the efficiency of SSC transplantation and reductions in SSC loss[ 84 ]. Increasing research results support the potential use of SSCs to restore fertility in clinical applications[ 85 ]. At present, it is generally believed that providing a good microenvironment for SSCs can achieve the goal of using these cells for fertility preservation.…”

Section: Spermatogonial Stem Cells and Their Nichementioning

confidence: 99%

Stem cell-based therapies for fertility preservation in males: Current status and future prospects

Liu¹,

Xie²,

Deng³

et al. 2020

WJSC

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With the decline in male fertility in recent years, strategies for male fertility preservation have received increasing attention. In this study, by reviewing current treatments and recent publications, we describe research progress in and the future directions of stem cell-based therapies for male fertility preservation, focusing on the use of spermatogonial stem cells (SSCs), SSC niches, SSC-based testicular organoids, other stem cell types such as mesenchymal stem cells, and stem cell-derived extracellular vesicles. In conclusion, a more comprehensive understanding of the germ cell microenvironment, stem cell-derived extracellular vesicles, and testicular organoids will play an important role in achieving male fertility preservation.

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“…Cryopreservation of testicular tissue before gonadotoxic treatment is increasingly used for fertility preservation in prepubertal boys, in whom spermatogonia are the only germ cell type present (19).…”

Section: Testicular Tissue Cryopreservationmentioning

confidence: 99%

“…However, this approach is still regarded as an experimental procedure and for the majority of centres it is conducted as a part of an ethically approved clinical research study (19,20).…”

Section: Testicular Tissue Cryopreservationmentioning

confidence: 99%

Yardimci Üreme Tekni̇kleri̇ Ve Ferti̇li̇te Prezervasyonunda Kri̇yoprezervason

Kahyaoğlu

Take

2020

Jinekoloji-Obstetrik Ve Neonatoloji Tıp Dergisi

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Cryopreservation is the technique of keeping living cells or tissues at ultralow temperature that no metabolic or biochemical activity can ocur. The use of cryopreservation techniques is highly attractive and has been increasingly applied worldwide. Cryopreservation of sperm, oocytes and embryos have been central to improvements in the assisted reproduction treatment success with many potential applications. Embryo cryopreservation is an established procedure and has been increasingly used due to novel indications as freeze-all strategy to reduce complications of assisted reproduction as ovarian hyperstimulation syndrome, pre-implantation genetic screening or single embryo transfer and cryopreservation of the remaining embryos to minimize the risk of multiple pregnancies. Sperm and oocyte cryopreservation has permitted the long term storage of gametes for patients with anticipated fertility decline. Ovarian and testicular tissue cryopreservation is the treatment options for prepubertal girls and boys requiring fertility preservation. Although they are relatively new techniques compared to gamete or embryo cryopreservation, they are both very promising and expected to be more widely implemented into the clinic in the near future.

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FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges

Cited by 24 publications

References 77 publications

Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer

Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer

Stem cell-based therapies for fertility preservation in males: Current status and future prospects

Yardimci Üreme Tekni̇kleri̇ Ve Ferti̇li̇te Prezervasyonunda Kri̇yoprezervason

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