Generation of the chemotherapy-induced POI mouse model and reversal of POI characteristics after intraovarian injection of hBM-MSC. (A) Representative image of the mouse vaginal swab sampling in each estrous cycle (scale bar size: 100 µm). (B) Average cycle length of control and POI mice (n = 6/group). (C) Histological analysis of mouse ovary from a normal mouse (control), POI mouse (POI), and hBM-MSC-treated POI mouse (MSC). H&E staining images for general morphology and folliculogenesis (upper), immunohistochemistry assay using CD31 for angiogenesis (middle), TUNEL assay for ovarian apoptosis (lower) (scale bar size: 300 µm). (D-E) Quantification of CD31 expression (D) and TUNEL positivity (E) in the ovary. (F-G) Comparison of ovarian tissue RNA expression between control, POI, and MSC mice. Relative gene expression level of the FSHR gene (F) and Cyp19 gene (G). (H) Morphology and marker protein expression in mouse endometrium (scale bar size: 300 µm) (*P < 0.05, **P < 0.01, ***P < 0.001).
ERα: estrogen receptor α; hBM-MSC: human bone marrow-derived mesenchymal stem cell; H&E: hematoxylin and eosin; POI: primary ovarian insufficiency; PR: progesterone receptor.