Department of Clinical Embryology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, India.
Department of Pathology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, India.
Reprod Sci. 2021 Aug;28(8):2161-2173. doi: 10.1007/s43032-020-00396-z. Epub 2020 Dec 15.
Cryopreservation of immature-testicular-tissue (ITT) prior to gonadotoxic treatment, while experimental, is the only recommended option for fertility preservation in prepubertal boys. The handling and manipulation of ITT before cryopreservation could influence the functionality of cells during fertility restoration, which this study explored by evaluating cellular niche and quality of mouse ITT subjected to various temperatures and time durations in vitro. ITT from 6-day-old mice were handled at ultraprofound-hypothermic, profound-hypothermic, and mild-warm-ischemic temperatures for varying time periods prior to 14-day organotypic culture. Viability, functionality, synaptonemal complex and chromatin remodeling markers were assessed. Results have shown that cell viability, testosterone level, and in vitro proliferation ability did not change when ITT were held at ultraprofound-hypothermic-temperature up to 24 h, whereas cell viability was significantly reduced (P < 0.01), when held at profound-hypothermic-temperature for 24 h before culture. Further, cell viability and testosterone levels in cultured cells from profound-hypothermic group were comparable to corresponding ultraprofound-hypothermic group but with moderate reduction in postmeiotic cells (P < 0.01). In conclusion, holding ITT at ultraprofound-hypothermic-temperature is most suitable for organotypic culture, whereas short-term exposure at profound-hypothermic-temperature may compromise postmeiotic germ cell yield post in vitro culture. This data, albeit in mouse model, will have immense value in human prepubertal fertility restoration research.
在性腺毒性治疗前对未成熟睾丸组织(ITT)进行冷冻保存,虽然是实验性的,但这是对青春期前男孩进行生育力保存的唯一推荐选择。在冷冻保存之前对 ITT 的处理和操作可能会影响细胞在生育力恢复过程中的功能,本研究通过评估在不同温度和时间下体外培养的小鼠 ITT 的细胞生态位和质量来探索这一点。对来自 6 天大的小鼠的 ITT 在超深低温、深低温和温和温热缺血温度下进行不同时间的处理,然后进行 14 天的器官型培养。评估了细胞活力、功能、联会复合体和染色质重塑标志物。结果表明,当 ITT 在超深低温下保持长达 24 小时时,细胞活力、睾酮水平和体外增殖能力没有变化,而当在培养前在深低温下保持 24 小时时,细胞活力显著降低(P < 0.01)。此外,来自深低温组的培养细胞的细胞活力和睾酮水平与相应的超深低温组相当,但减数后细胞数量减少(P < 0.01)。总之,将 ITT 保持在超深低温下最适合器官型培养,而在深低温下短期暴露可能会损害体外培养后减数后生殖细胞的产量。虽然这是在小鼠模型中,但这些数据将对人类青春期前生育力恢复研究具有巨大价值。