Abstract
Background: Polycystic ovarian syndrome (PCOS) is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of granulosa cells (GCs) proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation.Methods: USP25 and PTEN expression in GCs from women with and without PCOS was analyzed using Western blotting. A PCOS-like mouse model was constructed using USP25 knockout and wild-type mice to explore the role of USP25 in PCOS. The human granular cell line KGN was cultured for proliferation and apoptosis assays, and the effect of USP25 on PTEN was investigated after transfection with shRNA-USP25 lentivirus.Results: USP25 expression was found to be elevated in patients and mice with PCOS. With mouse model, we observed a reduction in PCOS symptoms in mice after USP25 deletion. Increased proliferation, reduced apoptosis, activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and decreased PTEN expression were found in KGN cells after USP25 knockdown. Finally, we verified that USP25 could deubiquitinate PTEN in KGN cells.Conclusions: In this study, we investigated that USP25 can regulate the PI3K/AKT signaling pathway by deubiquitinating PTEN, thus affecting the proliferation and apoptosis of GCs and contributing to the pathogenesis of PCOS.
Highlights
In reproductive-aged women, polycystic ovarian syndrome (PCOS) is a prevalent and diverse endocrine condition
Protein lysates were precleared with magnetic protein A/G beads (MedChemExpress) for 30 min before immunoprecipitation with ubiquitin-specific peptidase 25 (USP25) or PTEN antibody or corresponding normal immunoglobulin G (IgG) at 4◦C overnight
To further verify our hypothesis, we used coimmunoprecipitation assays to examine the ubiquitination of PTEN in KGN cells, and the results showed that decreased USP25 expression resulted in increased PTEN ubiquitination (Figure 6I)
Summary
In reproductive-aged women, polycystic ovarian syndrome (PCOS) is a prevalent and diverse endocrine condition. Degeneration, and hypertrophy of the granulosa cell layers surrounding these follicles indicate aberrant proliferation and/or apoptosis (Broekmans and Fauser, 2006). Follicular growth can be delayed due to decreases in small antral follicle GCs proliferation and increases in GCs apoptosis, which are thought to play essential roles in the pathogenesis of PCOS (Zhao et al, 2018; Geng et al, 2021). Polycystic ovarian syndrome (PCOS) is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of granulosa cells (GCs) proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation
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