男性生育力恢复:使用冷冻睾丸组织的体内和体外基于干细胞的策略 - 范围界定审查。
Male fertility restoration: In vivo and In vitro stem cell-based strategies using cryopreserved testis tissue - A scoping review.
发表日期:2024 Jul 09
作者:
Elena von Rohden, Christian Fuglesang S Jensen, Claus Yding Andersen, Jens Sønksen, Jens Fedder, Jørgen Thorup, Dana A Ohl, Mikkel Fode, Eva R Hoffmann, Linn Salto Mamsen
来源:
Epigenetics & Chromatin
摘要:
儿童癌症治疗的进步显着提高了生存率,超过 80% 的幸存者能够活到成年。然而,性腺毒性癌症治疗会危及未来的生育能力,青春期前的男性没有选择通过精子冷冻保存来保持生育能力。此外,患有隐睾症的男孩在成年后面临生育能力受损的风险。本次范围审查的重点是男性生育能力的恢复,特别是与青春期前男性癌症幸存者和患有隐睾症的男孩相关。目的是调查生育力恢复策略的当前证据,探索临床实施的障碍,并概述克服这些障碍的潜在步骤。该审查是按照 PRISMA-ScR 标准和之前发布的指南进行的,并检查了使用青春期前的人类睾丸组织的研究男孩或健康的男性成年人。在 PubMed 中进行了文献检索,发现了 72 项相关研究,包括体内和体外方法。睾丸组织植入和精原干细胞 (SSC) 移植等体内策略有望促进细胞存活和分化。然而,完整的精子发生尚未实现。体外方法侧重于在各种培养系统中通过直接生殖细胞成熟产生雄性生殖细胞,以及人类诱导多能干细胞(iPSC)和胚胎干细胞(ESC)。这些方法标志着理解和促进精子发生方面的重大进步,但在体外实现功能齐全的精子仍然是一个挑战。临床实施的障碍包括重新引入恶性细胞和引入表观遗传变化的风险。男性生育力恢复是一个快速发展的领域。根据综述的研究,使用冷冻保存的睾丸组织恢复男性生育力的最有前途和最先进的策略是直接睾丸组织移植。本综述确定了男性生育力恢复临床实施的持续障碍。然而,冻融睾丸组织的直接移植仍然是一种有前景的策略,即将进入临床应用。版权所有 © 2024。由 Elsevier Inc. 出版。
Advances in the treatment of childhood cancer have significantly improved survival rates, with more than 80% of survivors reaching adulthood. However, gonadotoxic cancer treatments endanger future fertility and prepubertal males have no option to preserve fertility by sperm cryopreservation. Also, boys with cryptorchidism are at risk of compromised fertility in adulthood.This scoping review focuses on male fertility restoration, particularly relevant for prepubertal male cancer survivors and boys with cryptorchidism. The aim was to investigate current evidence for fertility restoration strategies, explore barriers to clinical implementation, and outline potential steps to overcome these barriers.The review was conducted following the PRISMA-ScR criteria and previously published guidelines and examines studies using human testis tissue of prepubertal boys or healthy male adults. A literature search in PubMed was conducted and 72 relevant studies were identified, including in vivo and in vitro approaches.In vivo strategies, such as testis tissue engraftment and spermatogonial stem cell (SSC) transplantation, hold promise for promoting cell survival and differentiation. Yet complete spermatogenesis has not been achieved. In vitro approaches focus on the generation of male germ cells from direct germ cell maturation in various culture systems, alongside human induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs). These approaches mark significant advancements in understanding and promoting spermatogenesis but achieving fully functional spermatozoa in vitro remains a challenge. Barriers to clinical implementation include the risk of reintroducing malignant cells and introduction of epigenetic changes.Male fertility restoration is an area in rapid development. Based on the reviewed studies the most promising and advanced strategy for restoring male fertility using cryopreserved testis tissue is direct testis tissue transplantation.This review identifies persistent barriers to the clinical implementation of male fertility restoration. However, direct transplantation of frozen-thawed testis tissue remains a promising strategy that is on the verge of clinical application.Copyright © 2024. Published by Elsevier Inc.