Rg1 combined with hAD-MSC transplantation significantly improved ovarian function in chemotherapy-induced (POI) rats.
hAD-MSC transplantation increased the expression of the antiapoptotic protein Bcl-2.
The combination of Rg1 and hAD-MSCs decreased the expression of proapoptotic proteins and inhibited granulosa cell apoptosis.
Rats receiving the combination treatment showed reduced ovarian injury compared to those receiving hAD-MSCs alone.
In vitro studies indicated that Rg1 enhanced the antiapoptotic effects of hAD-MSCs on granulosa cells.
The underlying mechanisms may involve the PI3K/Akt-mitochondrial pathway, which is associated with apoptosis regulation.
Simplified
BACKGROUND: (POI) can cause multiple sequelae in young women and is currently incurable. Mesenchymal stem cell (MSC)-based treatment of POI shows great promise. However, some limitations affect their efficacy in POI treatment, and exploration of methods to improve their efficacy is necessary. This study aimed to explore whether Rg1 can improve the efficacy of human amnion-derived MSC (hAD-MSC) transplantation in the treatment of rats with chemotherapy-induced POI.
METHODS: hAD-MSCs were isolated from human amnions. One hundred female SD rats were divided into control, POI, Rg1, hAD-MSCs and Rg1 + hAD-MSCs groups. POI rat models were first established by intraperitoneal injection of cisplatin, and then the rats in the hAD-MSCs and Rg1 + hAD-MSCs groups were injected with PKH26-labelled hAD-MSCs via tail veins, while the rats in the Rg1 and Rg1 + hAD-MSCs groups were intraperitoneally injected with Rg1. At 24 h, 4 and 8 weeks after cell transplantation, serum sex hormone levels, oestrous cycles, ovarian pathological changes, granulosa cell (GC) apoptosis and antiapoptotic and proapoptotic protein expression in ovaries were evaluated. A chemotherapy-induced injury model of GCs was established by treatment with cisplatin in vitro to investigate the underlying mechanisms.
RESULTS: hAD-MSC transplantation significantly increased Bcl-2 expression; decreased Bax, cleaved-caspase-3, cleaved-caspase-9 and cleaved-PARP expression; and inhibited GC apoptosis in POI ovaries, which reduced ovarian injury and improved ovarian function in chemotherapy-induced POI rats; and the effects of hAD-MSC transplantation were significantly improved by Rg1 combined with hAD-MSC transplantation. Moreover, the enhanced efficacy of hAD-MSCs by Rg1 combined with hAD-MSCs in the inhibition of ovarian GC apoptosis was demonstrated in a chemotherapy injury model of GCs induced by cisplatin in vitro. The mechanisms might involve the modulatory role of Rg1 on both transplanted hAD-MSCs and GCs in the ovaries of POI rats, which indirectly and directly promoted the antiapoptotic effects on ovarian GCs, respectively, and the PI3K/Akt-mitochondrial intrinsic pathway of apoptosis may be a vital target pathway involved in these processes.
CONCLUSION: Rg1 may promote the efficacy of hAD-MSC transplantation in alleviating chemotherapy-induced POI in rats. Rg1 might be a novel adjuvant drug to promote the efficacy of MSCs in the treatment of chemotherapy-induced POI.
Key numbers
100% of rats
Regular Oestrous Cycles
All control group rats exhibited regular oestrous cycles.
Higher in + group than in group
AMH and E2 Levels
AMH and E2 levels were significantly improved at 4 and 8 weeks after transplantation.
Lower in + group
Apoptotic Protein Expression
Proapoptotic proteins were significantly reduced in the + group compared to the group.
Full Text
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Declarations. Ethics approval and consent to participate: The research was in compliance with the Helsinki Declaration and approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University. Written informed consent was obtained from all donors before collecting amnion. Animal experimental protocols were approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University in March 25, 2020. The approved project was entitled “Effects of Ginsenoside Rg1 combined with human amnion-derived mesenchymal stem cells (hAD-MSCs) on the chemotherapy-induced premature ovarian insufficiency (POI) (permit number 2020-20) ”. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
PubMed
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