P-591 Follicular fluid-derived exosomes rejuvenate ovarian aging through miR-320a-3p-mediated FOXQ1 inhibition

Abstract Study question Dose the follicular fluid-derived exosomes rejuvenate ovarian aging? Summary answer Follicular fluid-derived exosomes efficiently rescued ovarian function in aged mice, which was achieved via transfer of miR-320-3p to granulosa cells and subsequent Foxq1 inhibition. What is known already The ovary enters the malfunctional aging phase earlier and faster than other organs and systems. Ovarian aging is mainly characterized by a progressive decline in oocyte quantity and quality, which ultimately leads to female infertility. Various therapies have been established to cope with age-related ovarian dysfunction, among which exosome-based therapy has been considered a promising strategy that can benefit ovarian functions via multiple pathways. Study design, size, duration Ovarian granulosa cells of young C57BL/6J mice (6-8 w) and old C57BL/6J mice (40 w) were cultured in vitro. The follicular fluid exosomes of young mice and the same amount of PBS were respectively injected into the ovarian sac of old mice. Participants/materials, setting, methods Cell proliferation and apoptosis were detected by CCK8, flow cytometry and Western Blot. Mitochondrial function was assessed by measuring mitochondrial membrane potential, ATP levels, mtDNA copy numbers. The number of ovarian follicles were observed by HE staining. Senescence and telomere related gene expression levels were detected by RT-qPCR. 2-cell rates and blastocyst formation rates were observed after in vitro fertilization. The model mice were directly cooped up to observe the pregnat and litter sizes. Main results and the role of chance The follicular fluid exosomes from young mice can promote the proliferation of ovarian granulosa cells from old mice and improve mitochondrial function. When the follicular fluid exosomes from young mice were injected into the ovarian sac of old mice, the number of primordial and growing follicles in the ovaries of old mice were increased and the developmental ability of oocytes was improved. Limitations, reasons for caution Findings in mouse. Wider implications of the findings This study suggests that young follicular fluid exosomes may be involved in ovarian senescence by transferring miR-320a-3p targeting FOXQ1 into ovarian granulosa cells of aged mice. Trial registration number no