INSERM, U1239, Team Adrenal and Gonadal Pathophysiology, Laboratory of Neuroendocrine Endocrine and Germinal Differentiation and Communication, Rouen University Hospital, Rouen Normandy University, 76000, Rouen, France.
Sci Rep. 2022 May 6;12(1):7407. doi: 10.1038/s41598-022-11286-6.
The assessment of the impact of chemotherapies on in vitro spermatogenesis in experimental models is required before considering the application of this fertility restoration strategy to prepubertal boys who received these treatments before testicular tissue cryopreservation. The present work investigated the effects of exposure of prepubertal mice to mono- (vincristine or cyclophosphamide) and polychemotherapy (a combination of vincristine and cyclophosphamide) on the first wave of in vitro spermatogenesis. When testicular tissue exposed to monochemotherapy was preserved, polychemotherapy led to severe alterations of the seminiferous epithelium and increased apoptosis in prepubertal testes prior in vitro maturation, suggesting a potential additive gonadotoxic effect. These alterations were also found in the testicular tissues of polychemotherapy-treated mice after 30 days of organotypic culture and were associated with a reduction in the germ cell/Sertoli cell ratio. The different treatments neither altered the ability of spermatogonia to differentiate in vitro into spermatozoa nor the yield of in vitro spermatogenesis. However, more spermatozoa with morphological abnormalities and fragmented DNA were produced after administration of polychemotherapy. This work therefore shows for the first time the possibility to achieve a complete in vitro spermatogenesis after an in vivo exposure of mice to a mono- or polychemotherapy before meiotic entry.
在考虑将这种生育力恢复策略应用于接受化疗后进行睾丸组织冷冻保存的青春期前男孩之前，需要评估化疗对实验模型中体外精子发生的影响。本研究探讨了暴露于未成年小鼠的单药（长春新碱或环磷酰胺）和多药化疗（长春新碱和环磷酰胺的组合）对体外精子发生的第一波影响。当暴露于单药化疗的睾丸组织被保存时，多药化疗导致未成年睾丸在体外成熟前的生精上皮严重改变，并增加凋亡，提示潜在的附加性腺毒性作用。在多药化疗处理的小鼠的睾丸组织经过 30 天的器官型培养后也发现了这些改变，并且与生殖细胞/支持细胞比例降低有关。不同的处理既没有改变精原细胞在体外分化为精子的能力，也没有改变体外精子发生的产量。然而，多药化疗后产生的精子中出现更多形态异常和 DNA 碎片化的精子。因此，本研究首次表明，在进入减数分裂之前，体内暴露于单药或多药化疗的小鼠可以实现完全的体外精子发生。
