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多囊卵巢综合征中脂质代谢基因的异常表达和 DNA 甲基化：对其发病机制的新认识。

Aberrant expression and DNA methylation of lipid metabolism genes in PCOS: a new insight into its pathogenesis.

机构信息

1The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030 China.

2The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, Zhejiang 310006 China.

出版信息

Clin Epigenetics. 2018 Jan 12;10:6. doi: 10.1186/s13148-018-0442-y. eCollection 2018.

DOI:10.1186/s13148-018-0442-y
PMID:29344314
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5767000/
Abstract

BACKGROUND

Polycystic ovary syndrome (PCOS), whose etiology remains uncertain, is a highly heterogenous and genetically complex endocrine disorder. The aim of this study was to identify differentially expressed genes (DEGs) in granulosa cells (GCs) from PCOS patients and make epigenetic insights into the pathogenesis of PCOS.

RESULTS

Included in this study were 110 women with PCOS and 119 women with normal ovulatory cycles undergoing in vitro fertilization acting as the control group. RNA-seq identified 92 DEGs unique to PCOS GCs in comparison with the control group. Bioinformatic analysis indicated that synthesis of lipids and steroids was activated in PCOS GCs. 5-Methylcytosine analysis demonstrated that there was an approximate 25% reduction in global DNA methylation of GCs in PCOS women (4.44 ± 0.65%) compared with the controls (6.07 ± 0.72%;  < 0.05). Using MassArray EpiTYPER quantitative DNA methylation analysis, we also found hypomethylation of several gene promoters related to lipid and steroid synthesis, which might result in the aberrant expression of these genes.

CONCLUSIONS

Our results suggest that hypomethylated genes related to the synthesis of lipid and steroid may dysregulate expression of these genes and promote synthesis of steroid hormones including androgen, which could partially explain mechanisms of hyperandrogenism in PCOS.

摘要

背景

多囊卵巢综合征（PCOS）的病因尚不清楚，是一种高度异质性和遗传复杂的内分泌疾病。本研究旨在鉴定多囊卵巢综合征患者颗粒细胞（GCs）中的差异表达基因（DEGs），并从表观遗传学角度探讨 PCOS 的发病机制。

结果

本研究纳入了 110 名 PCOS 患者和 119 名接受体外受精的正常排卵周期女性作为对照组。RNA-seq 鉴定出与对照组相比，PCOS GCs 中存在 92 个独特的 DEGs。生物信息学分析表明，PCOS GCs 中脂质和类固醇的合成被激活。5-甲基胞嘧啶分析表明，与对照组（6.07±0.72%；  < 0.05）相比，PCOS 女性 GCs 的全基因组 DNA 甲基化水平降低了约 25%（4.44±0.65%）。使用 MassArray EpiTYPER 定量 DNA 甲基化分析，我们还发现与脂质和类固醇合成相关的几个基因启动子存在低甲基化，这可能导致这些基因的异常表达。

结论

我们的研究结果表明，与脂质和类固醇合成相关的低甲基化基因可能会使这些基因的表达失调，并促进包括雄激素在内的类固醇激素的合成，这可以部分解释 PCOS 中高雄激素血症的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/9205ceb4b0e5/13148_2018_442_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/2a8488049fcc/13148_2018_442_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/d059d29bd5a4/13148_2018_442_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/190d341c5431/13148_2018_442_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/c983a3b30ffa/13148_2018_442_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/9205ceb4b0e5/13148_2018_442_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/2a8488049fcc/13148_2018_442_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/d059d29bd5a4/13148_2018_442_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/190d341c5431/13148_2018_442_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/c983a3b30ffa/13148_2018_442_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/5767000/9205ceb4b0e5/13148_2018_442_Fig5_HTML.jpg

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