Time to bloom: Safeguarding and restoring male fertility

This dissertation focuses on fertility preservation and restoration in boys who are at risk of infertility after gonadotoxic cancer treatment. In contrast to adult men, boys who have not yet reached puberty are unable to cryopreserve sperm prior to treatment, as spermatogenesis has not yet initiated. Instead, testicular tissue containing spermatogonial stem cells can be collected and cryopreserved. However, methods to restore fertility from this immature tissue remain experimental and are not yet available in clinical practice.
The research described in this dissertation aimed to improve understanding of the biological and technical requirements needed to advance fertility preservation and restoration strategies. The effects of different cryopreservation methods on immature human testicular tissue and the potential for subsequent fertility restoration were investigated. The response of Sertoli cells to platinum-based chemotherapy was examined, with particular focus on the maintenance of Sertoli cell function. Given the central role of Sertoli cells in supporting germ cell development, their maturation was subsequently characterised alongside germ cell development in human testicular tissue from foetal life through puberty. Building on this knowledge, an organotypic mouse testicular tissue culture model was used to investigate to what extent spermatogenesis can be reproduced in vitro. In addition, automated image analysis was explored to improve the reproducibility and efficiency of testicular tissue assessment. This dissertation contributes to the ongoing search for safe and effective strategies to restore fertility in childhood cancer survivors, with the future aim of enabling boys who preserve testicular tissue before treatment to have the possibility of biological parenthood later in life.