Guan Chun-Yi, Zhang Dan, Sun Xue-Cheng, Ma Xu, Xia Hong-Fei
Reproductive and Genetic Center and NHC Key Laboratory of Reproductive Health Engineering Technology Research National Research Institute for Family Planning (NRIFP), Beijing 100081, China.
Graduate School Peking Union Medical College, Beijing 100005, China.
Stem Cells Int. 2024 Jul 30;2024:3100942. doi: 10.1155/2024/3100942. eCollection 2024.
The ovary is an important organ for women to maintain reproductive and endocrine functions. Ovarian aging can lead to female reproductive aging, which is a key factor causing rapid aging of the female body. Umbilical cord-derived MSCs (UC-MSCs) play a therapeutic role in various degenerative diseases. Dehydroepiandrosterone (DHEA) is widely used in the treatment of reversing oocyte quality. However, it is unclear whether UC-MSCs combined with DHEA supplementation can improve ovarian senescence in naturally aging mice. To address this question, we studied the influence of the combination of human UC-MSCs (hUC-MSCs) and DHEA on ovarian morphology and function in naturally aging mice. The results showed a significant augmentation in the number of primary follicles, as well as a significant upregulation of estradiol (E2), follicle-stimulating hormone (FSH), and anti-Mullerian hormone (AMH) hormone levels, and a significant increase in survival rate in naturally aging mice treated by hUC-MSCs and DHEA. Moreover, the combination of hUC-MSCs and DHEA significantly reduced the reactive oxygen species (ROS) level and downregulated the expression levels of proinflammatory factors IL-6, IL-18, and TNF-. Furthermore, the PI3K/AKT/mTOR pathway was inhibited. Conclusively, the combination therapy of hUC-MSC + DHEA contributed to restore ovarian function in aging mice and extend their lifespan by restoring hormone levels and inhibiting inflammatory factors.
卵巢是女性维持生殖和内分泌功能的重要器官。卵巢衰老会导致女性生殖衰老，这是导致女性身体快速衰老的关键因素。脐带间充质干细胞（UC-MSCs）在各种退行性疾病中发挥治疗作用。脱氢表雄酮（DHEA）被广泛用于改善卵母细胞质量的治疗。然而，尚不清楚UC-MSCs联合补充DHEA是否能改善自然衰老小鼠的卵巢衰老。为了解决这个问题，我们研究了人脐带间充质干细胞（hUC-MSCs）与DHEA联合使用对自然衰老小鼠卵巢形态和功能的影响。结果显示，在接受hUC-MSCs和DHEA治疗的自然衰老小鼠中，初级卵泡数量显著增加，雌二醇（E2）、卵泡刺激素（FSH）和抗苗勒管激素（AMH）水平显著上调，存活率显著提高。此外，hUC-MSCs与DHEA联合使用显著降低了活性氧（ROS）水平，并下调了促炎因子IL-6、IL-18和TNF-的表达水平。此外，PI3K/AKT/mTOR通路受到抑制。总之，hUC-MSC+DHEA联合疗法有助于恢复衰老小鼠的卵巢功能，并通过恢复激素水平和抑制炎症因子来延长其寿命。
