Cell-Free Fat Extract Improves Ovarian Function and Fertility in Mice With Advanced Age.
Cell-Free Fat Extract Improves Ovarian Function and Fertility in Mice With Advanced Age.
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无细胞脂肪提取物可改善高龄小鼠的卵巢功能和生育能力
DOI：
10.3389/fendo.2022.912648
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发表时间：
2022
影响因子：
5.2
通讯作者：
Xu, Bufang
中科院分区：
文献类型：
--
作者：
Liu, Mengyu;Li, Wenzhu;Zhou, Xiaowei;Zhou, Mingjuan;Zhang, Wenjie;Liu, Qiang;Zhang, Aijun;Xu, Bufang
关键词：
卵母细胞数量和质量的下降是影响高龄妇女生育能力的主要因素，高龄妇女往往推迟生育，生育率下降。然而，在临床实践中缺乏有效的治疗策略来对抗这种卵巢功能的下降。因此，有必要确定一种新的方法来挽救卵巢功能并改善生育能力自然年龄相关性下降的生殖能力。无细胞脂肪提取物（CEFFE）已被证实具有多种活性蛋白质，发挥抗衰老和促进增殖的作用。尽管如此，CEFFE是否可以挽救与年龄相关的卵巢功能下降并改善高龄女性的生育能力仍不清楚。本研究采用小鼠自然衰老模型，观察CEFFE对卵巢功能的抗衰老作用。我们发现，通过静脉注射CEFFE可以恢复自然衰老小鼠模型中性激素水平，增加血管生成和生长卵泡数量。此外，CEFFE促进胚胎发育，增加老龄小鼠的产仔数。老年小鼠卵巢的转录组分析显示，CEFFE治疗上调了参与DNA损伤修复的基因的表达。体内外实验均证实CEFFE能改善颗粒细胞的功能，包括促进颗粒细胞增殖、延缓衰老、挽救衰老颗粒细胞DNA损伤等。综上所述，本研究提示CEFFE通过改善卵巢整体微环境，改善自然衰老小鼠的卵巢功能和生育能力，为卵巢无细胞治疗提供了新的抗衰老治疗策略的理论依据。
The reduction in the quantity and quality of oocytes is the major factor affecting fertility in women with advanced age, who tend to experience delayed childbearing and declined fertility rate. However, effective therapeutic strategies to combat this decrease in ovarian function are lacking in clinical practice. Thus, identifying a new method to rescue ovarian function and improve reproduction in natural age-related decline in fertility is necessary. Cell-free fat extract (CEFFE) has been verified to possess diverse active proteins exerting anti-aging and proliferation-promoting effects. Nonetheless, whether CEFFE can rescue the decline in aged-related ovarian function and improve the fertility of females with advanced age remains unclear. In this study, a natural aging mouse model, exhibiting similarities to the physiological changes of ovarian senescence, was used to observe the anti-aging effect of CEFFE on ovarian functions. We found that CEFFE, injected via the veins, could recover the levels of the sex hormone, increase angiogenesis and the number of growth follicles in the natural aging mice model. Moreover, CEFFE promoted the development of embryos and increased the litter size of aged mice. Transcriptome analysis of the aged mouse ovaries revealed that CEFFE treatment upregulated the expression of genes involved in the repair of DNA damage. And both in vivo and in vitro experiment proved that CEFFE improved the function of granulosa cells, including promoting proliferation, alleviating senescence, and rescuing DNA damage in aged granulosa cells. Collectively, our study implied that CEFFE improved the ovarian function and fertility of naturally aging mice by ameliorating the overall microenvironment of ovary, which provided a theoretical basis for new anti-aging therapeutic strategies for cell-free therapy in ovaries.
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影响因子：
168.9
作者：
Christensen, Kaare;Doblhammer, Gabriele;Rau, Roland;Vaupel, James W.
通讯作者：
Vaupel, James W.
影响因子：
5.2
作者：
Ishizuka B
通讯作者：
Ishizuka B
DOI：
10.1093/humrep/deab106
发表时间：
2021-06-18
期刊：
Human reproduction (Oxford, England)
影响因子：
--
作者：
Atkinson L;Martin F;Sturmey RG
通讯作者：
Sturmey RG
影响因子：
6.7
作者：
Dumesic, Daniel A.;Meldrum, David R.;Schoolcraft, William B.
通讯作者：
Schoolcraft, William B.
影响因子：
56.9
作者：
Gruhn, Jennifer R.;Zielinska, Agata P.;Hoffmann, Eva R.
通讯作者：
Hoffmann, Eva R.