When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome?

Saen, Dorien Van; Vloeberghs, Veerle; Gies, Inge; Mateizel, Ileana; Sermon, Karen; Schepper, Jean De; Tournaye, Herman; Goossens, Ellen

doi:10.1093/humrep/dey094

Cited by 71 publications

(92 citation statements)

References 43 publications

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“…KS is associated with hypogonadism and infertility with fewer than half of adult men reported to have spermatozoa present in the ejaculate, although residual foci with spermatogenesis may be present in some individuals with apparent azoospermia [134]. The testicular phenotype of KS involves a progressive loss of spermatogonial stem cells (SSC) beginning in prepuberty, with testicular fibrosis occurring in (peri)pubertal and adult patients [135]. A meta-analysis of the presence of spermatogonia in individuals with KS demonstrated spermatogonia in the testes of all fetal/infantile samples, 83% of those obtained from prepubertal patients, and in 40-50% of adolescent/adult individuals [20].…”

Section: Klinefelter Syndromementioning

confidence: 99%

“…Furthermore, the underlying testicular and germ cell abnormalities in individuals with KS may result in additional challenges for the use of this approach for fertility preservation. Therefore, this approach has recently been called into question [135] and testicular tissue cryopreservation in prepubertal patients should only be considered as part of an ethically approved research study.…”

Section: Klinefelter Syndromementioning

confidence: 99%

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Disorders of Sex Development—Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation

Gomes

Chetty

Jørgensen

et al. 2020

IJMS

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Disorders (or differences) of sex development (DSD) are a heterogeneous group of congenital conditions with variations in chromosomal, gonadal, or anatomical sex. Impaired gonadal development is central to the pathogenesis of the majority of DSDs and therefore a clear understanding of gonadal development is essential to comprehend the impacts of these disorders on the individual, including impacts on future fertility. Gonadal development was traditionally considered to involve a primary ‘male’ pathway leading to testicular development as a result of expression of a small number of key testis-determining genes. However, it is increasingly recognized that there are several gene networks involved in the development of the bipotential gonad towards either a testicular or ovarian fate. This includes genes that act antagonistically to regulate gonadal development. This review will highlight some of the novel regulators of gonadal development and how the identification of these has enhanced understanding of gonadal development and the pathogenesis of DSD. We will also describe the impact of DSDs on fertility and options for fertility preservation in this context.

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Section: Klinefelter Syndromementioning

confidence: 99%

Section: Klinefelter Syndromementioning

confidence: 99%

Disorders of Sex Development—Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation

Gomes

Chetty

Jørgensen

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Thus, from a fertility point of view, it should be noted that infertility is common and that less than half of the adult men reported by Corona et al [68] had sperm in their ejaculation, although, in some individuals with apparent azoospermia, there may be residual foci with spermatogenesis. Van Saen et al [69] reported that there is a progressive loss of spermatogonial stem cells that begins at prepubertal time, with frequent testicular fibrosis by adulthood. A meta-analysis of the presence of spermatogonia in individuals with KS demonstrated their presence in the testes of all fetal/infant samples, in 83% of those obtained from prepubertal patients, and in 40-50% of adolescents/adults [70].…”

Section: Klinefelter Syndrome (Ks)mentioning

confidence: 99%

“…However, the underlying abnormalities in the testes and germ cells of individuals with KS may create additional challenges for the use of this approach for fertility preservation. Thus, this approach has recently been questioned [69], and cryopreservation of testicular tissue in prepubertal patients should only be considered as part of an ethically approved research study [41].…”

Section: Klinefelter Syndrome (Ks)mentioning

confidence: 99%

Disorders of Sex Development: Classification, Review, and Impact on Fertility

Acién

2020

JCM

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In this review, the elements included in both sex determination and sex differentiation are briefly analyzed, exposing the pathophysiological and clinical classification of disorders or anomalies of sex development. Anomalies in sex determination without sex ambiguity include gonadal dysgenesis, polysomies, male XX, and Klinefelter syndrome (dysgenesis and polysomies with a female phenotype; and sex reversal and Klinefelter with a male phenotype). Other infertility situations could also be included here as minor degrees of dysgenesis. Anomalies in sex determination with sex ambiguity should (usually) include testicular dysgenesis and ovotesticular disorders. Among the anomalies in sex differentiation, we include: (1) males with androgen deficiency (MAD) that correspond to those individuals whose karyotype and gonads are male (XY and testes), but the phenotype can be female due to different hormonal abnormalities. (2) females with androgen excess (FAE); these patients have ovaries and a 46,XX karyotype, but present varying degrees of external genital virilization as a result of an enzyme abnormality that affects adrenal steroid biosynthesis and leads to congenital adrenal hyperplasia; less frequently, this can be caused by iatrogenia or tumors. (3) Kallman syndrome. All of these anomalies are reviewed and analyzed herein, as well as related fertility problems.

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“…Furthermore, pre-existing impairment to the testicular somatic environment of the recipient testis may prevent further germ cell development. 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).…”

Section: Pre-existing Testicular Pathologymentioning

confidence: 86%

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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When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome?

Cited by 71 publications

References 43 publications

Disorders of Sex Development—Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation

Disorders of Sex Development—Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation

Disorders of Sex Development: Classification, Review, and Impact on Fertility

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

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