Women with diminished ovarian reserve (DOR) have reduced fertility, but the underlying regulation of ovarian function remains unknown. Although differential microRNA (miRNA) expression has been described in several ovarian disorders, little is known about the role of miRNAs in the pathogenesis of DOR. In this study, we investigated the expression levels of miR-484 in granulosa cells (GCs) derived from human follicular fluid, and explored their correlation with female ovarian reserve function as well as clinical outcomes of assisted reproduction technology (ART). Additionally, we investigated the effects of miR-484 on the biological functions of GC cell lines in vitro. We found that miR-484 was highly expressed in GCs from DOR patients and was correlated with decreasing AMH levels and AFC, as well as increasing FSH levels, but not with LH, progesterone, or estradiol. Additionally, miR-484 was negatively related to the number of retrieved oocytes and the ratio of high-quality embryos. Moreover, we found that miR-484 repressed the proliferation of GCs and induced apoptosis, which can in part be attributed to mitochondrial dysfunction. Conversely, silencing miR-484 had the opposite effect. Multiple approaches, including bioinformatic analysis, RNA-seq, qPCR, immunofluorescence, western blotting and luciferase reporter assays, identified YAP1 as a direct target of miR-484 in GCs. Additionally, reintroduction of YAP1 rescued the effects of miR-484 in GCs. The present study indicates that miR-484 can directly target the mRNA of YAP1, induce mitochondrial dysfunction, and consequently reduce the viability and promote the apoptosis of granulosa cells, which contributes to the pathogenesis of DOR.

With the development of regenerative medicine, stem cells are being considered more frequently for the treatment of reproductive aging. Human umbilical cord mesenchymal stem cells have been reported to improve the reserve function of aging ovaries through their homing and paracrine effects. In this process, paracrine factors secreted by stem cells play an important role in ovarian recovery. Although the transplantation of human umbilical cord mesenchymal stem cells to improve ovarian function has been studied with great success in animal models of reproductive aging, their application in clinical research and therapy is still relatively rare. Therefore, this paper reviews the role of human umbilical cord mesenchymal stem cells in the treatment of reproductive aging and their related mechanisms, and it does so in order to provide a theoretical basis for further research and clinical treatment.

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N6-methyladenosine (m 6 A) is the most prevalent chemical modification in eukaryotic messenger RNAs. By participating in various RNA-related bioprocesses including RNA decay, splicing, transport and translation, m 6 A serves as a pivotal regulator of RNA fate and plays an irreplaceable role in cellular activities. The m 6 A modifications of transcripts are coordinately regulated by methyltransferase "writers" and demethylase "erasers", and produce variable effects via different m 6 A reading protein "readers". There is emerging evidence that m 6 A modifications play a critical role in a variety of physiological and pathological processes in the female reproductive system, subsequently affecting female fertility. Here, we introduce recent advances in research on m 6 A regulators and their functions, then highlight the role of m 6 A in gonad development and female reproductive diseases, as well as the underlying mechanisms driving these processes.

In this study, we successfully constructed the new graphene oxide/poly- L -lactic acid (GO/PLLA) nanofiber scaffolds with a hydrophilic surface and porous network structure that were highly favorable for cell infiltration. When employed these new nanofiber scaffolds for a wide range of tissue engineering applications, it was expected to promote graft tissue survival and angiogenesis. The new GO/PLLA nanofiber scaffold with an appropriate concentration of 1.0 wt% was applied for the restoration of ovarian function and reserve in mice with primary ovarian insufficiency (POI). After co-transplanting the normal ovarian cortex loaded on these new nanomaterials into the in situ ovarian tissue of POI mice, the fusion of transplanted ovarian cortex with damaged ovarian tissue was improved, as well as the ovarian function and the follicle numbers. Moreover, angiogenesis was observed clearly and proved to exist in the transplanted tissue and nanomaterials, with the most conspicuous effect after co-transplantation with 1.0 wt% GO/PLLA nanofiber scaffold. In addition, nitric oxide (NO) production by phosphorylated endothelial nitric oxide synthase (p-eNOS) in vivo was proven to be involved in the effect of GO and PLLA on the improved survival rate of the transplanted ovarian cortex. This study provides a new method for the fertility preservation of ovarian tissue cryopreservation and transplantation, as well as a new strategy for the transplantation of other organs.