Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China.
Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Ovarian Res. 2024 Feb 1;17(1):28. doi: 10.1186/s13048-024-01345-z.
Sestrins have been implicated in regulating aging in various organs through multiple pathways. However, their roles in ovarian aging remain unrevealed.
Female Sestrin1, Sestrin2, and Sestrin3 mice were generated using the CRISPR-Cas9 system. Body weights, little sizes, ovarian weights, estrous cyclicity, and follicle number in female mice were observed. ELISA was utilized to measure serum anti-Müllerian hormone (AMH) levels. Real time PCR, western blot, immunofluorescence, and Masson trichrome staining were employed for assessment of aging-related change.
The deletion of Sestrin 1, 2, or 3 had no discernible impact on body weights,or serum AMH levels in female mice at the age of 12 months. And there were no discernible differences in litter sizes or estrous cyclicity which were assessed at the age of 8 months. At the age of 12 months, no significant differences were observed in ovarian weights or follicle numbers among the knockout mice. Consistently, the extent of fibrosis within the ovaries remained comparable across all experimental groups at this age. Additionally, autophagy, apoptosis, DNA damage, and inflammation within the ovaries were also found to be comparable to those in wild-type mice of the same age.
The loss of Sestrin 1, 2, or 3 does not exert a noticeable influence on ovarian function during the aging process. Sestrin1, 2, and 3 are not essential for female fertility in mice.
Sestrins 通过多种途径参与调节各种器官的衰老。然而,它们在卵巢衰老中的作用仍未被揭示。
使用 CRISPR-Cas9 系统生成雌性 Sestrin1、Sestrin2 和 Sestrin3 敲除小鼠。观察雌性小鼠的体重、阴道开口大小、卵巢重量、动情周期和卵泡数量。采用 ELISA 法测定血清抗苗勒管激素(AMH)水平。实时 PCR、western blot、免疫荧光和 Masson 三色染色用于评估与衰老相关的变化。
在 12 月龄的雌性小鼠中,Sestrin1、2 或 3 的缺失对体重或血清 AMH 水平没有明显影响。在 8 月龄时,窝仔数或动情周期也没有明显差异。在 12 月龄时,敲除小鼠的卵巢重量或卵泡数之间没有显著差异。同样,在这个年龄,所有实验组的卵巢纤维化程度也没有差异。此外,卵巢内的自噬、细胞凋亡、DNA 损伤和炎症也与同年龄的野生型小鼠相似。
Sestrin1、2 或 3 的缺失在衰老过程中对卵巢功能没有明显影响。Sestrin1、2 和 3 对小鼠的雌性生育力不是必需的。