Microenvironmental changes by placenta-derived mesenchymal stem cells restore the ovarian function in ovariectomized rat via activated PI3K-FOXO3 pathway

Abstract

Background: Translational studies have explored the therapeutic potential and feasibility of mesenchymal stem cells (MSCs) in several degenerative diseases; however, the mechanistic studies of the function of these cells have been insufficient. As ovarian failures cause anovulation as well as ovarian steroid hormonal unbalances, the specific aims of this study were to analyze the therapeutic role of placenta derived MSCs (PD-MSCs) in an ovarian-failure ovariectomy (OVX) rat model and evaluate whether PD-MSCs transplantation (Tx) improved folliculogenesis and oocyte maturation in the injured ovary through PI3K/Akt and FOXO signaling. Methods: Blood and ovary tissue were collected and analyzed after various PD-MSCs Tx treatments in the ovariectomized rat model. Changes in the expression of folliculogenesis and ovary regeneration-related genes due to PD-MSCs treatments were analyzed by qRT-PCR, Western blotting, and histological analysis. Results: The levels of hormones related to ovary function were significantly increased in the PD-MSCs Tx groups compared with those of the non-transplantation group (NTx). The follicle numbers in the ovarian tissues were increased along with increased expression of genes related to folliculogenesis for PD-MSCs Tx compared with NTx groups. Furthermore, PD-MSCs Tx induced maturation of follicles by increasing the phosphorylation of GSK3 beta and FOXO3 (p<0.05) and shifting the balance of growth and apoptosis in the oocytes. Conclusions: Taken together, PD-MSCs Tx can restore the ovarian function as well as induce ovarian folliculogenesis via the PI3K/Akt and FOXO signaling pathway.