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

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.

A novel long-term intravenous combined with local treatment with human amnion-derived mesenchymal stem cells for a multidisciplinary rescued uremic calciphylaxis patient and the underlying mechanism

“…hAMSCs were prepared in the State Key Laboratory of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital ( Liu et al, 2021b ), a Good Manufacturing Practice (GMP)-compliant laboratory according to the national principle ( ‘Guiding Principle for Cell Therapy Products Research and Assessment Technique’, 2017 ).…”

Apoptotic vesicles resist oxidative damage in noise-induced hearing loss through activation of FOXO3a-SOD2 pathway

“…6 c), indicating that SOD2 gene transcription was promoted by apoVs treatment. As a result, we looked through transcription factors which can regulate transcription of SOD2 gene according to previous studies, in which we found out FOXO3a (Forkhead box O3) [ 44 ]. The location of FOXO3a in cells depends on its activation state.…”

Drug-free in vitro activation combined with 3D-bioprinted adipose-derived stem cells restores ovarian function of rats with premature ovarian insufficiency

“…Therefore, the future studies should concentrate on promoting early post-transplantation revascularization and improving fertility associated with age-related declines in oocyte quality. Numerous studies have demonstrated that mesenchymal stem cells (MSCs) could significantly stimulate neovascularization and increase blood perfusion to reduce the loss of primordial follicles [ 15 , 16 ] and effectively improve the quality and number of oocytes in aged mice [ 17 – 19 ]. This represents a new strategy toward boosting fertility in women with reduced ovarian reserve.…”