Human amnion-derived mesenchymal stem cells improved the reproductive function of age-related diminished ovarian reserve in mice through Ampk/FoxO3a signaling pathway

Stem Cell Research & Therapy

Youjia Yu¹  Feng Chen¹  Meilian Wang²  Li Chen²  Yugui Cui³  Yuexin Zhang³  Chunyan Jiang³  Boya La³  Jiayin Liu³  Lianju Qin³  Zhengjie Yan³  Chuyu Li³  Hanwen Liu³  Xiang Ma³  Song Ning³  Huimin Wu³  Jing Zhou³  Meng Cao³ 

[1] Department of Forensic Medicine, Nanjing Medical University;Department of Obstetrics, First Affiliated Hospital, Nanjing Medical University;State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University;

关键词: Age-related diminished ovarian reserve;    Human amnion-derived mesenchymal stem cells;    Granulosa and stromal cells;    AMPK/FoxO3a signaling pathway;    Oxidation resistance;    Mitophagy;   

DOI  :  10.1186/s13287-021-02382-x

来源: DOAJ

【 摘 要 】

Abstract Background Age-related diminished ovarian reserve (AR-DOR) reduced the quality of oocytes, resulting in decreased female fertility. Aging is tightly related to abnormal distribution and function of mitochondria, while mitophagy is a major process to maintain normal quality and quantity of mitochondria in cells, especially in oocytes which containing a large number of mitochondria to meet the demand of energy production during oocyte maturation and subsequent embryonic development. Ampk/FoxO3a signaling is crucial in the regulation of mitophagy. It is reported mesenchymal stem cells (MSCs) can improve ovarian function. Here we aim to explore if human amnion-derived mesenchymal stem cells (hAMSCs) are effective in improving ovarian function in AR-DOR mice and whether Ampk/FoxO3a signaling is involved. Methods The AR-DOR model mice were established by 32-week-old mice with 3–8 litters, significantly low serum sex hormone levels and follicle counts. The old mice were divided into 5 treatment groups: normal saline (NS, control), 1% human serum albumin (HSA, resolver), low dose (LD, 5.0 × 106cells/kg), middle dose (MD, 7.5 × 106cells/kg), and high dose (HD, 10.0 × 106cells/kg). The prepared hAMSCs were injected through tail vein. Serum sex hormone level, follicle counts, fertilization rate, gestation rate, little size, apoptosis of granulosa and stromal cells, expression level of Sod2, Ampk, and ratio of phosphorylated FoxO3a to total FoxO3a in ovaries were examined. Results Our results show that after hAMSC transplantation, the ovarian function in AR-DOR mice was significantly improved, meanwhile the apoptosis of granulosa and stromal cells in the ovaries was significantly repressed, the expression level of Ampk and the ratio of phosphorylated FoxO3a to total FoxO3a both were significantly increased, meanwhile increased Sod2 expression was also observed. Conclusion Our results demonstrate hAMSC transplantation via tail-injection can improve ovarian function of AR-DOR mice through Ampk/FoxO3a signaling pathway.

【 授权许可】

Unknown