Institut national de la recherche scientifique, Centre INRS - Institut Armand-Frappier, QC, Canada.
Division of Urology, McGill University Health Center, QC, Canada.
Adv Exp Med Biol. 2019;1166:189-203. doi: 10.1007/978-3-030-21664-1_11.
Fertility is a growing healthcare issue for a rising number of cancer survivors. In men, cancer itself and its treatment can negatively affect spermatogenesis by targeting the dividing spermatogonia and their cellular environment, ultimately leading to a reduction of testicular germ cells and sperm count. Experimental data and prospective longitudinal studies have shown that sperm production can recover after cancer treatment. But despite this, yet unpredictable, recovery in sperm production, cancer survivors are more at risk to produce sperm with aneuploidy, DNA damage, abnormal chromatin structure, and epigenetic defects even 2 years post-treatment. Sperm DNA alteration is of clinical concern, as these patients may father children or seek assisted reproduction technologies (ART) using gametes with damaged genome that could result in adverse progeny outcomes. Interestingly, large cohort studies revealed lower birth rate but no significant impact on the health of the children born from male cancer survivors (naturally or using ART). Nevertheless, a better understanding of how cocktail of chemotherapy and new anticancer agents affect spermatogenesis and sperm quality is needed to reduce side effects. Moreover, developing new fertility preservation strategies is essential as sperm cryopreservation before treatment is currently the only option but does not apply for prepubertal/young postpubertal patients.
生育能力是越来越多癌症幸存者面临的一个日益严重的医疗保健问题。在男性中，癌症本身及其治疗方法会通过靶向分裂的精原细胞及其细胞环境，对生精作用产生负面影响，最终导致睾丸生殖细胞和精子数量减少。实验数据和前瞻性纵向研究表明，癌症治疗后精子的产生可以恢复。但是，尽管如此，精子的产生仍可能无法预测地恢复，癌症幸存者更有可能产生非整倍体、DNA 损伤、异常染色质结构和表观遗传缺陷的精子，即使在治疗后 2 年也是如此。精子 DNA 改变是临床关注的问题，因为这些患者可能生育子女，或者使用基因组受损的配子寻求辅助生殖技术（ART），这可能导致后代出现不良后果。有趣的是，大型队列研究表明，男性癌症幸存者（自然生育或使用 ART）的出生率较低，但对其后代的健康没有显著影响。然而，需要更好地了解化疗和新型抗癌药物如何影响生精作用和精子质量，以减少副作用。此外，开发新的生育力保存策略至关重要，因为目前治疗前精子冷冻保存是唯一的选择，但不适用于青春期前/年轻青春期后的患者。
