A diagnostic germ cell score for immature testicular tissue at risk of germ cell loss

Heckmann, Laura; Langenstroth-Röwer, Daniel; Pock, Tim; Wistuba, Joachim; Stukenborg, Jan-Bernd; Zitzmann, Michael; Kliesch, Sabine; Schlatt, Stefan; Neuhaus, Nina

doi:10.1093/humrep/dey025

Cited by 39 publications

(30 citation statements)

References 30 publications

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“…Similarly, for patients with Klinefelter syndrome, apparent loss of germ cells has been reported prior to puberty, with the appearance of fibrosis in peri-puberty (Van Saen et al 2018). An overall reduction in spermatogonial numbers have also been reported in peripubertal testes from Klinefelter patients compared to controls (Heckmann et al 2018). However, the timing of the loss of spermatogonia cannot be accurately determined from these studies.…”

Section: Pre-existing Testicular Pathologymentioning

confidence: 96%

“…A potential limiting factor for development of autologous SSC transplantation is the number of SSCs that can be obtained for transplantation. The SSC population is relatively rare and recent studies using human prepubertal testis tissue have demonstrated the limited quantity of spermatogonia within the testis, which may also be negatively influenced by underlying disease or previous treatments (Poganitsch-Korhonen et al 2017, Heckmann et al 2018) and the small size of biopsy material. Whilst efficient isolation of SSC using specific cellsurface markers is a focus for current research and may significantly increase the yield of human SSC (Zohni et al 2012, Nickkholgh et al 2014a, Valli et al 2014, it is likely that in vitro propagation of the SSC population will also be required in order to generate sufficient SSC to restore fertility in patients.…”

Section: In Vitro Propagation Of Sscsmentioning

confidence: 99%

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

Kilcoyne

Mitchell

2019

Reproduction

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Transplantation of testicular tissues and cells has been proposed as a future clinical option for patients who have had testicular tissue cryopreserved prior to receiving gonadotoxic therapies. Whilst this approach remains experimental, success using animal models and successful transplantation of ovarian tissue resulting in live births in female patients provides optimism for the development of clinical applications involving transplantation of testicular tissue in males. Careful consideration must be given to patient groups that may benefit from this approach in the future. Current research is focused on optimising patient selection, methods for tissue cryopreservation and development of transplantation techniques that might restore sperm production or future fertility in males. Crucially, attention must be focused on ensuring safety of transplantation, including eliminating the potential for infection or re-introducing malignancy. Furthermore the genetic/epigenetic integrity of any gametes generated must be ensured to allow generation of normal offspring. This review will provide an overview of the current status of transplantation of testicular tissue and cells for fertility preservation in males.Reproduction (2019) 158 F1-F14

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Section: Pre-existing Testicular Pathologymentioning

confidence: 96%

Section: In Vitro Propagation Of Sscsmentioning

confidence: 99%

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

Kilcoyne

Mitchell

2019

Reproduction

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“…Testicular volumes were determined by palpation using a Prader orchidometer [40] and, in most cases, additionally confirmed by ultrasonography (Table 1). Surgery and testis biopsy collection were performed as previously described [5,41]. The majority of the biopsy was cryopreserved for clinical fertility preservation and the remaining part was fixed in (diluted) Bouin's solution and further processed for histological analysis.…”

Section: Immature Patientsmentioning

confidence: 99%

“…Reasons for this include pathological conditions such as cryptorchidism and genetic or endocrine disorders [1][2][3][4][5]. Apart from that, cancer therapy and conditioning treatments of non-malignant diseases such as sickle cell disease and thalassemia, are known to induce testicular damage, affect spermatogonial function and reduce or even deplete germ cells [4][5][6][7][8][9][10]. Consequently, gonadotoxic treatment may lead to temporary or permanent infertility depending on treatment dose and duration, patients' age and underlying diagnosis [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Descriptive and qualitative information of the heterogeneous prepubertal testicular tissues is pivotal to determine its potential use in fertility restoration strategies. While accumulating evidence on spermatogonial numbers in bio-banked tissues is reported, evaluation of molecular properties of spermatogonia remains limited [4,5,9,10,15].…”

Section: Introductionmentioning

confidence: 99%

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Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues

Portela

Heckmann²,

Wistuba³

et al. 2020

JCM

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Cancer therapy and conditioning treatments of non-malignant diseases affect spermatogonial function and may lead to male infertility. Data on the molecular properties of spermatogonia and the influence of disease and/or treatment on spermatogonial subpopulations remain limited. Here, we assessed if the density and percentage of spermatogonial subpopulation changes during development (n = 13) and due to disease and/or treatment (n = 18) in tissues stored in fertility preservation programs, using markers for spermatogonia (MAGEA4), undifferentiated spermatogonia (UTF1), proliferation (PCNA), and global DNA methylation (5mC). Throughout normal prepubertal testicular development, only the density of 5mC-positive spermatogonia significantly increased with age. In comparison, patients affected by disease and/or treatment showed a reduced density of UTF1-, PCNA- and 5mC-positive spermatogonia, whereas the percentage of spermatogonial subpopulations remained unchanged. As an exception, sickle cell disease patients treated with hydroxyurea displayed a reduction in both density and percentage of 5mC- positive spermatogonia. Our results demonstrate that, in general, a reduction in spermatogonial density does not alter the percentages of undifferentiated and proliferating spermatogonia, nor the establishment of global methylation. However, in sickle cell disease patients’, establishment of spermatogonial DNA methylation is impaired, which may be of importance for the potential use of this tissues in fertility preservation programs.

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Germ cell loss in Klinefelter syndrome: When and why?

Willems

Gies

Saen

2020

American J of Med Genetics Pt C

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Klinefelter syndrome (KS) is a quite common disorder with an incidence of 1-2 in 1000 newborn males. Most patients are diagnosed in the light of a clinical check-up when consulting a fertility clinic with an unfulfilled child wish. Infertility in KS patients is caused by a massive germ cell loss, leading to azoospermia in more than 90% of the adult patients. Most seminiferous tubules in the adult KS testis are degenerated or hyalinized and testicular fibrosis can be observed, starting from puberty. However, focal spermatogenesis can be found in the testis of some patients. This offers the opportunity to extract spermatozoa from the testis by testicular sperm extraction. However, TESE is only successful in about half of the KS adults seeking to father children. The reason for the germ cell loss remains unclear. To date, it is still debated whether the testicular tissue changes and the germ cell loss seen in KS is directly caused by an altered X-linked gene expression, the altered somatic environment or a deficiency in the germ cells. In this review, we provide an overview of the current knowledge about the germ cell loss in KS patients.

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A diagnostic germ cell score for immature testicular tissue at risk of germ cell loss

Abstract: This study was supported by the Funding Initiative: Translational Research, Ministry of Innovation, Science and Research, Federal State of North Rhine Westphalia (z1403ts006). The authors declare that they do not have competing financial interests.

Cited by 39 publications

References 30 publications

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

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

Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues

Germ cell loss in Klinefelter syndrome: When and why?

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