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.

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.

Background Resistant ovary syndrome (ROS) is a rare endocrine disorder and there have been few reports of live births by affected patients. As gonadotropin resistance leads immature oocytes, some researchers reported few live births with in vitro maturation (IVM) of oocytes, but IVM is not always successful in ROS patients. Here, we report an original case of ROS, associated with Ig-FSHR in the serum, who achieved a live birth following ovarian stimulation combined with dexamethasone treatment. Case presentation The 30-year-old woman presented with secondary amenorrhea and infertility. Her serum FSH levels were found to be higher than normal, but in discordance with a normal anti-Müllerian hormone (AMH) level and antral follicle count. Genetic investigation found no mutations potentially affecting FSHR. With reference of previous ROS studies, the patient’s serum was analyzed for antibodies directed against FSHR and dot blot analysis showed strong reactivity with FSHR. Then, dexamethasone was proposed to the patient, and she successfully became pregnant, finally delivering a healthy girl by caesarean section. Conclusion To our best knowledge, this is the first report of the successful treatment of ROS using ovarian stimulation combined with dexamethasone. In some cases of ROS, high doses of exogenous gonadotropins in combination with immunosuppressive therapy could be an effective approach.

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