1. YTHDF2 regulates MSS51 expression contributing to mitochondria dysfunction of granulosa cells in polycystic ovarian syndrome patients.
- Author
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Jiao YY, Song N, Fang XY, Lu XT, Sun N, Jin HX, Chen L, Huang XJ, Wen S, Wu ZT, Wang XP, Cheng TT, Yao GD, and Song WY
- Subjects
- Humans, Female, Adult, Reactive Oxygen Species metabolism, Gene Expression Regulation, Adenosine Triphosphate metabolism, Glycolysis genetics, Mitochondrial Proteins metabolism, Mitochondrial Proteins genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Polycystic Ovary Syndrome genetics, Polycystic Ovary Syndrome metabolism, Polycystic Ovary Syndrome pathology, Granulosa Cells metabolism, Granulosa Cells pathology, Mitochondria metabolism, Mitochondria genetics, RNA-Binding Proteins metabolism, RNA-Binding Proteins genetics
- Abstract
Research Question: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients?, Design: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition., Results: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM., Conclusions: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients., Competing Interests: Declaration of competing interest All authors have declared that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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