补充自体脂肪干细胞来源的线粒体可以成为一种安全且有前途的改善卵母细胞质量的策略。
Supplementation with autologous adipose stem cell-derived mitochondria can be a safe and promising strategy for improving oocyte quality.
机构信息
HORAC Grand Front Osaka Clinic, Osaka, Japan.
Reproductive Science Institute, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
出版信息
J Assist Reprod Genet. 2024 Aug;41(8):2065-2077. doi: 10.1007/s10815-024-03137-2. Epub 2024 May 22.
PURPOSE
In our previous study, we confirmed that the supplementation of vitrified-warmed murine oocytes with autologous adipose stem cell (ASC)-derived mitochondria during intracytoplasmic sperm injection enhances post-fertilization developmental competence in mice. To ensure the safety of this technology, we conducted a thorough study in mice to investigate the potential presence of specific malformations in offspring developed from this approach.
METHODS
A transgenerational comparative analysis was conducted on founder mice from embryos that developed after mitochondrial supplementation, and two subsequent generations. Reproductive performance, body growth rate, histopathological parameters, hematological parameters, daily activity patterns, and daily body temperature changes in male and female mice across these three generations were assessed in comparison to wild-type mice of the same age.
RESULTS
Both male and female animals in all three generations showed comparable reproductive performance to the control group. Additionally, body growth rate by the age of 8 weeks were found to be comparable to controls across all three generations. Notably, no significant histopathological abnormalities were detected in vital organs, including the brain, heart, liver, kidneys, lungs, ovaries, and testes, in any individuals from the studied cohorts. The blood parameters were consistent with the control data. The continuous monitoring of activity and body temperature changes (both day and night) over a 1-week period revealed a pattern closely resembling that observed in the control animals.
CONCLUSION
Injection of ASC-mitochondria into oocytes may be a promising technique to support developmental potential without causing adverse epigenetic events in the offspring in mice. However, before considering clinical application, additional safety screening using larger animals or non-human primates is essential.
目的
在我们之前的研究中，我们证实了在胞质内精子注射过程中，向玻璃化解冻的小鼠卵母细胞中补充自体脂肪干细胞（ASC）衍生的线粒体，可增强小鼠受精后的发育能力。为确保该技术的安全性，我们在小鼠中进行了一项全面的研究，以调查从这种方法中发育而来的后代是否存在特定畸形的可能性。
方法
对来自经线粒体补充后发育的胚胎的创始小鼠以及随后的两代进行了跨代比较分析。对三代小鼠的雄性和雌性生殖性能、体生长率、组织病理学参数、血液学参数、日常活动模式和日体温变化进行了评估，并与同年龄的野生型小鼠进行了比较。
结果
所有三代动物的雄性和雌性动物的生殖性能均与对照组相当。此外，在所有三代中，8 周龄时的体生长率与对照组相当。值得注意的是，在所研究的队列中，没有在任何个体的重要器官（包括大脑、心脏、肝脏、肾脏、肺、卵巢和睾丸）中发现明显的组织病理学异常。血液参数与对照数据一致。对 1 周内的活动和体温变化（白天和夜间）进行连续监测，结果显示出与对照组非常相似的模式。
结论
将 ASC 线粒体注入卵母细胞可能是一种有前途的技术，可以在不引起后代表观遗传事件的情况下支持发育潜能。然而，在考虑临床应用之前，使用较大的动物或非人类灵长类动物进行额外的安全性筛选是必不可少的。
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