miR-644-5p carried by bone mesenchymal stem cell-derived exosomes targets regulation of p53 to inhibit ovarian granulosa cell apoptosis

Abstract

Abstract Background This article aims to reveal the therapeutic effects and potential mechanisms of bone mesenchymal stem cell (BMSC)-derived exosomes on premature ovarian failure (POF). Methods Exosomes were collected from BMSCs and were used to treat cisplatin-induced POF mouse models. Pathological changes of ovarian tissue were detected by using HE staining and by Western blot that detected the expression of apoptosis-related proteins. In cisplatin-induced primary granulosa cell injury, exosomes were co-cultured with the granulosa cells. The apoptosis or viability of granulosa cells was analyzed by flow cytometry or MTT, respectively. In Target scan and microT-CDS databases, an intersection of miRNAs targeting to p53 was found. The expressions of miRNAs in BMSC-derived exosomes were detected by qRT-PCR. Besides, miR-664-5p targeted to p53 of cells was verified by dual-luciferase reporter assay. Results BMSC-derived exosomes improved the follicular morphology of POF mice and inhibited the expression of apoptosis-related protein. By co-culture of exosomes and primary granulosa cells, BMSC-derived exosomes repressed cisplatin-induced granulosa cells apoptosis and increased cells viability, while these effects were abrogated after the exosome-containing RNA was degraded by RNase. By Target scan, microT-CDS and qRT-PCR, miR-664-5p was regarded as the dominated RNA in BMSC-derived exosomes. By dual-luciferase reporter assay, miR-664-5p negatively regulated p53 luciferase activity. After shRNA interfering miR-664-5p of BMSC, BMSC-derived exosomes exerted no protective effect on cisplatin-induced granulosa cell apoptosis. Conclusion Our results indicated that miR-644-5p carried by BMSC-derived exosomes inhibited the apoptosis of ovarian granulosa cell by targeting p53 of cells, suggesting that miR-644-5p had the potential to treat POF and restore ovarian function.