Mouse germ cells go through typical epigenetic modifications after intratesticular tissue grafting

Goossens, Ellen; Bilgec, T.; Saen, Dorien Van; Tournaye, Herman

doi:10.1093/humrep/der334

Cited by 37 publications

(36 citation statements)

References 37 publications

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“…After SSCT and TTG with fresh samples, neither numerical chromosomal alterations, nor epigenetic modifications were detected in spermatozoa (Goossens et al ., 2009, 2010, 2011). Extended cell manipulation and exposition to digestive and cryoprotective solutions, plus the hurdle of cryopreservation itself, may induce modifications in the germ line cells, e.g.…”

Section: Resultsmentioning

confidence: 99%

“…changes in DNA methylation, or chromosomal abnormalities. Indeed, the disruption of SSCs from their niche might influence the establishment of correct epigenetic patterns and thus the development of spermatozoa arising from the possibly altered SSC (Goossens et al ., 2011). Oocytes fertilized by spermatozoa arising from epigenetically altered SSCs develop abnormally.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Cryopreservation of testicular tissue or testicular cell suspensions: a pivotal step in fertility preservation

Onofre

Baert

Faes

et al. 2016

Hum. Reprod. Update

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153

116

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BACKGROUNDGerm cell depletion caused by chemical or physical toxicity, disease or genetic predisposition can occur at any age. Although semen cryopreservation is the first reflex for preserving male fertility, this cannot help out prepubertal boys. Yet, these boys do have spermatogonial stem cells (SSCs) that able to produce sperm at the start of puberty, which allows them to safeguard their fertility through testicular tissue (TT) cryopreservation. SSC transplantation (SSCT), TT grafting and recent advances in in vitro spermatogenesis have opened new possibilities to restore fertility in humans. However, these techniques are still at a research stage and their efficiency depends on the amount of SSCs available for fertility restoration. Therefore, maintaining the number of SSCs is a critical step in human fertility preservation. Standardizing a successful cryopreservation method for TT and testicular cell suspensions (TCSs) is most important before any clinical application of fertility restoration could be successful.OBJECTIVE AND RATIONALEThis review gives an overview of existing cryopreservation protocols used in different animal models and humans. Cell recovery, cell viability, tissue integrity and functional assays are taken into account. Additionally, biosafety and current perspectives in male fertility preservation are discussed.SEARCH METHODSAn extensive PubMED and MEDline database search was conducted. Relevant studies linked to the topic were identified by the search terms: cryopreservation, male fertility preservation, (immature)testicular tissue, testicular cell suspension, spermatogonial stem cell, gonadotoxicity, radiotherapy and chemotherapy.OUTCOMESThe feasibility of fertility restoration techniques using frozen-thawed TT and TCS has been proven in animal models. Efficient protocols for cryopreserving human TT exist and are currently applied in the clinic. For TCSs, the highest post-thaw viability reported after vitrification is 55.6 ± 23.8%. Yet, functional proof of fertility restoration in the human is lacking. In addition, few to no data are available on the safety aspects inherent to offspring generation with gametes derived from frozen-thawed TT or TCSs. Moreover, clarification is needed on whether it is better to cryopreserve TT or TCS.WIDER IMPLICATIONSFertility restoration techniques are very promising and expected to be implemented in the clinic in the near future. However, inter-center variability needs to be overcome and the gametes produced for reproduction purposes need to be subjected to safety studies. With the perspective of a future clinical application, there is a dire need to optimize and standardize cryopreservation and safety testing before using frozen-thawed TT of TCSs for fertility restoration.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Cryopreservation of testicular tissue or testicular cell suspensions: a pivotal step in fertility preservation

Onofre

Baert

Faes

et al. 2016

Hum. Reprod. Update

Self Cite

153

116

View full text Add to dashboard Cite

show abstract

“…However, it should be noted that recent studies raise concerns about possible misinterpretation of these human SSC propagation data [28][29][30][31]. In mice, it was reported that offspring obtained after spermatogonial stem cell transplantation did not show any relevant epigenetic changes too [32][33][34].…”

Section: Testicular Tissue Cryopreservation In Boysmentioning

confidence: 99%

Testicular Tissue Cryopreservation

Tournaye

Verheyen

Goossens

2016

Gonadal Tissue Cryopreservation in Fertility Preservation

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Loss of spermatogonial stem cells can be associated to ageing or can be part of genetic disorders such as 47,XXY Klinefelter syndrome. However, cytotoxic therapies and/or irradiation is the main cause of germ cell loss and can disrupt spermatogenesis temporarily or permanently. These therapies are not only used to treat malignant disorders but may also be used for benign haematological conditions that need bone-marrow transplantation.Since survival rates after cancer treatment are increasing, preservation of the reproductive potential has become an important quality of life issue for both adults but also for childhood cancer survivors. Adult men who cannot bank ejaculate spermatozoa can opt to cryopreserve surgically retrieved spermatozoa, i.e. testicular sperm. Prepubertal boys cannot benefit from sperm banking, but testicular stem cell banking is being introduced into more and more clinics. This strategy should still be regarded as experimental given the lack of any report on successful transplantation and the limited safety data of this method.

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“…In a study comparing sperm derived from SSCs in grafts versus sperm derived from SSCT, no DNA methylation changes were found between these groups, but transplantation-derived sperm showed some variation in histone 4 acetylation [64]. Aberrant histone acetylation at this stage in development might have limited significance because in humans 85–95% of all histones are replaced by protamines to ensure proper packaging of DNA before delivery [65].…”

Section: Epigenetics In Cultured Sscsmentioning

confidence: 99%

Restoring Fertility in Sterile Childhood Cancer Survivors by Autotransplanting Spermatogonial Stem Cells: Are We There Yet?

Struijk

Mulder

Veen

et al. 2013

BioMed Research International

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Current cancer treatment regimens do not only target tumor cells, but can also have devastating effects on the spermatogonial stem cell pool, resulting in a lack of functional gametes and hence sterility. In adult men, fertility can be preserved prior to cancer treatment by cryopreservation of ejaculated or surgically retrieved spermatozoa, but this is not an option for prepubertal boys since spermatogenesis does not commence until puberty. Cryopreservation of a testicular biopsy taken before initiation of cancer treatment, followed by in vitro propagation of spermatogonial stem cells and subsequent autotransplantation of these stem cells after cancer treatment, has been suggested as a way to preserve and restore fertility in childhood cancer survivors. This strategy, known as spermatogonial stem cell transplantation, has been successful in mice and other model systems, but has not yet been applied in humans. Although recent progress has brought clinical application of spermatogonial stem cell autotransplantation in closer range, there are still a number of important issues to address. In this paper, we describe the state of the art of spermatogonial stem cell transplantation and outline the hurdles that need to be overcome before clinical implementation.

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Mouse germ cells go through typical epigenetic modifications after intratesticular tissue grafting

Cited by 37 publications

References 37 publications

Cryopreservation of testicular tissue or testicular cell suspensions: a pivotal step in fertility preservation

Cryopreservation of testicular tissue or testicular cell suspensions: a pivotal step in fertility preservation

Testicular Tissue Cryopreservation

Restoring Fertility in Sterile Childhood Cancer Survivors by Autotransplanting Spermatogonial Stem Cells: Are We There Yet?

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