Exosomes released by bone marrow mesenchymal stem cell (BMSCs) provide a novel source and a
great potential donor cell for regenerative medicine. The current study was set to explore the restorative
potential of BMSCs derived exosomes in a rat model of premature ovarian failure (POF) and its
underlying mechanisms. Exosomes were prepared and infused to the cisplatin induced POF rats. The
ovaries were subjected for histological and immune-histochemical evaluation of survivin and Oct4. RNA
extraction and quantitative real time PCR were carried out for evaluation of Stra8, Oct4, Lin28, and
Nanos3 gene expression. Serum estradiol (E2) and follicular stimulating hormone (FSH) were
monitored. The POF group showed reduced number of follicles, excessive fibrosis, follicular atresia,
low serum E2 and high FSH levels compared to controls. BMSCs derived exosomes infusion improved
ovarian architecture with normal hormonal profile. There was down and up-regulation of Oct4 and
Lin28, markers of stemness and germ cell survival, Stra8 and Nanos3, molecules that judge the cellular
fate towards meiosis and oocyte formation in POF, and exosomes treated ovaries respectively. This
study demonstrate for the first time that exosomes infusion showed structural and functional reparative
properties,possibly through delivering its carriage of protein, molecular content and RNA bioactive
molecules to the host ovarian niche inducing neo-oogenesis/folliculogenesis. This provides an effective
and novel method for treatment of POF.