Abstract
A better understanding of the mechanism of primordial follicle activation will help us better understand the causes of premature ovarian insufficiency (POI), and will help us identify new drugs that can be applied to the clinical treatment of infertility. In this study, single oocytes were isolated from primordial and primary follicles, and were used for gene profiling with TaqMan array cards. Bioinformatics analysis was performed on the gene expression data, and Ingenuity Pathway Analysis was used to analyze and predict drugs that affect follicle activation. An ovarian in vitro culture system was used to verify the function of the drug candidates, and we found that curcumin maintains the ovarian reserve. Long-term treatment with 100 mg/kg curcumin improved the ovarian reserve indicators of AMH, FSH, and estradiol in aging mice. Mechanistic studies show that curcumin can affect the translocation of FOXO3, thereby inhibiting the PTEN-AKT-FOXO3a pathway and protecting primordial follicles from overactivation. These results suggest that curcumin is a potential drug for the treatment of POI patients and for fertility preservation.
Highlights
In the mammalian ovary, primordial follicles are the most basic unit and constitute the ovarian reserves [1]
We searched for genes related to the primordial follicle, primary follicle, and premature ovarian insufficiency (POI) in the Ingenuity Pathway Analysis (IPA) database, and used the Ovarian Kaleidoscope Database (OKdb)
Describing the the mechanism mechanism of lays thethe foundation for for the Describing of primordial primordialfollicle follicleactivation activation lays foundation identification of potential drugs that can activate follicles or protect the ovarian reserve, the identification of potential drugs that can activate follicles or protect the ovarian rethus providing the possibility for the treatment and prevention of POI
Summary
Primordial follicles are the most basic unit and constitute the ovarian reserves [1]. Several genes and pathways have been shown to play important roles in the activation of primordial follicles [3]. Some of these, such as GDF-9, Grem1/2, insulin, and BMP4/SMAD signaling [4,5,6,7], promote the activation of primordial follicles, while others, such as Lhx, Pten, and Tsc1/mTORC1 signaling, suppress follicle activation [8,9,10]. PTEN-AKT-FOXO3a is a key pathway that regulates the activation of primordial follicles [11,12,13]. The study of primordial follicle activation is significant for clinical research
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