Male infertility
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BITE (BIOLOGY OF THE TESTIS)
The research group BITE studies spermatogenesis with a special focus on spermatogonial stem cells (SSCs). SSC depletion, which is a major side effect of gonadotoxic treatment or the result of a genetic disorder, such as Klinefelter Syndrome, leads to infertility. Our current aim is to develop strategies to prevent infertility after SSC loss. Fertility can be preserved by either limiting the loss of gametes and their precursors or by storing gametes and/or their precursors. While adult men can bank their spermatozoa prior to gonadotoxic treatment (e.g. chemotherapy or radiotherapy), no options are available to preserve fertility in prepubertal boys, who do not have active spermatogenesis yet. Storing SSCs before starting gonadotoxic treatment may therefore be a strategy to prevent infertility on the long term. After being cured, SSCs may be reintroduced into the seminiferous tubules in order to regenerate spermatogenesis. Alternatively, testicular tissue containing SSCs may be grafted. However, this strategy is not possible for patients with Klinefelter Syndrome since the testes of these boys are sclerotized at adult age. For these patients in vitro spermatogenesis would be helpful.
Our research therefore focusses on:
- patient follow-up after childhood gonadotoxic treatment
- developing and implementing methods to transplant SSCs or testicular tissue
- generating sperm cells in vitro
- studying Klinefelter Syndrome - related infertility
Beschrijving van het project
In Europe, at least 20% of young men exhibit sperm parameters below the lower WHO reference level and this affects their fertility. Only for a small fraction of these patients, the cause of their infertility can be diagnosed, but in most infertile men, the reason for their infertility is unknown.
Techniques are available to retrieve sperm from patients with oligozoospermia from semen and in case of obstructive azoospermia by microsurgical epididymal sperm aspiration or testicular sperm extraction. The sperm may then be used for assisted reproductive technologies such as in-vitro fertilization or intracytoplasmic sperm injection. However, for men with non-obstructive azoospermia or prepubertal patients at risk for fertility loss (e.g. boys needing gonadotoxic cancer treatments), there are currently no therapeutic options available to father their genetically own child.
The spermatogonial stem cell (SSC) is the driving force behind spermatogenesis. Loss or dysfunction of SSCs results in male infertility. In cases where SSCs are the only germ cells present in the testis, in vivo or in vitro strategies based on sperm development from SSCs should be established. To develop these potential therapies is a huge task, because it requires detailed understanding of the entire process of sperm production from stem cells to functional sperm, and the regulation of each step in this process.
The research group BITE has performed pioneering work on in vivo strategies for fertility preservation in young boys needing gonadotoxic treatment (SSC transplantation and tissue grafting). These are now being translated to clinical applications. However, these in vivo strategies will not benefit young boys suffering from systemic or metastasizing cancers (risk for transplanting back malignant cells), patients with Klinefelter syndrome (sclerotic testes at adult age), and patients with non-obstructive azoospermia. These patients might benefit from in vitro strategies.
Our current research aims include
- the study of regulatory processes during germ cell maturation
- the study of mechanisms that lead to Klinefelter-related infertility
- the development of a 3D culture system for human in-vitro spermatogenesis
- the implementation of novel developments into the clinic