YTHDF2 regulates MSS51 expression contributing to mitochondria dysfunction of granulosa cells in polycystic ovarian syndrome patients

IF 3.8 3区 医学 Q2 CELL BIOLOGY Molecular and Cellular Endocrinology Pub Date : 2024-06-01 DOI:10.1016/j.mce.2024.112292
Yun-Yun Jiao , Ning Song , Xing-Yu Fang , Xiao-Tong Lu, Ning Sun, Hai-Xia Jin, Lei Chen, Xian-Ju Huang, Shuang Wen, Zhao-Ting Wu, Xiao-Peng Wang, Ting-Ting Cheng, Gui-Dong Yao, Wen-Yan Song
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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.

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YTHDF2调节MSS51的表达,导致多囊卵巢综合征患者颗粒细胞线粒体功能障碍
研究问题颗粒细胞(GCs)功能障碍在多囊卵巢综合征(PCOS)的发病机制中起着至关重要的作用。据报道,含YTH结构域的家族蛋白2(YTHDF2)在多囊卵巢综合征患者的壁层GC中上调。设计收集15例多囊卵巢综合征患者和15例排卵对照组的壁细胞和积液细胞,每组4例病理切片。采用实时 PCR、Western Blot、免疫组织化学和免疫荧光实验检测基因和蛋白质的表达。通过 RNA 免疫沉淀实验评估 YTHDF2 与 MSS51 的结合关系。结果 在本研究中,我们发现 YTHDF2 在 PCOS 患者的 GC 中上调,而 MSS51 则下调。YTHDF2蛋白可与MSS51 mRNA结合并影响MSS51的表达。结论YTHDF2可能调控MSS51的表达,影响GCs中线粒体的结构和功能,干扰细胞糖酵解,从而干扰PCOS患者GCs的正常生物学过程和卵泡发育。
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来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
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