Human amnion–derived mesenchymal stem cell (hAD-MSC) transplantation can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced primary ovarian insufficiency (POI). However, ensuring that stem cells home to the ovary to improve their effects on ovarian injury is challenging. This research aimed to directly inject ovarian tissue with hAD-MSCs and improve the homing of stem cells to the ovary. The animals were divided into POI, hAD-MSC (tail vein) treatment, hAD-MSC (in situ) treatment, and control groups. POI rat models were established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). The hAD-MSCs isolated from the amnion were injected into the tail vein or ovary of POI rats. The estrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, and proteome of the ovaries were evaluated. hAD-MSCs were successfully isolated and cultured from the amnion. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantation increased body weight, improved the AMH levels and follicle numbers, and reduced reproductive organ injuries in POI rats. Transplantation of hAD-MSCs (in situ) upregulated 24 proteins and downregulated 4 proteins. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantations can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced POI. The paracrine proteome of hAD-MSCs in the ovarian microenvironment can protect against chemotherapy-induced damage by reducing apoptosis and promoting angiogenesis, cell proliferation, and gene expression.
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The datasets used and/or analyzed during the current study are available from the corresponding author on a reasonable request.
primary ovarian insufficiency
enzyme-linked immunosorbent assay
fibroblast growth factor
hematoxylin and eosin
human amnion–derived mesenchymal stem cell
insulin-like growth factor
mesenchymal stem cell
optimal cutting temperature
premature ovarian failure
primary ovarian insufficiency
vascular endothelial growth factor
fetal bovine serum
analysis of variance
extracellular signal–regulated kinase
c-Jun N-terminal kinase
protein kinase B
platelet factor 4
mitogen-activated protein kinase
tumor necrosis factor
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This study was supported by the National Natural Science Foundation of China (81671415).
This research was in accordance with the Helsinki Declaration and approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University.
The authors declared that they have no conflict of interest.
Ethics Approval and Consent to Participate
The protocol was approved by the Committee on the Ethics of Animal Experiments of Chongqing Medical University (Permit Number: 2016-044).
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Feng, X., Ling, L., Zhang, W. et al. Effects of Human Amnion–Derived Mesenchymal Stem Cell (hAD-MSC) Transplantation In Situ on Primary Ovarian Insufficiency in SD Rats. Reprod. Sci. 27, 1502–1512 (2020). https://doi.org/10.1007/s43032-020-00147-0
- Primary ovarian insufficiency