Protein Lysine Acetylation in Ovarian Granulosa Cells Affects Metabolic Homeostasis and Clinical Presentations of Women With Polycystic Ovary Syndrome.
Protein Lysine Acetylation in Ovarian Granulosa Cells Affects Metabolic Homeostasis and Clinical Presentations of Women With Polycystic Ovary Syndrome.
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卵巢颗粒细胞中蛋白质赖氨酸乙酰化影响多囊卵巢综合征女性的代谢稳态和临床表现
DOI：
10.3389/fcell.2020.567028
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发表时间：
2020
影响因子：
5.5
通讯作者：
Qiao J
中科院分区：
文献类型：
--
作者：
Min Z;Long X;Zhao H;Zhen X;Li R;Li M;Fan Y;Yu Y;Zhao Y;Qiao J
多囊卵巢综合征（PCOS）是最常见的生殖内分泌疾病之一，伴有明显的代谢异常。在辅助生殖技术治疗过程中，PCOS妇女经常发现低质量的卵母细胞和胚胎。然而，PCOS患者卵巢代谢紊乱的机制及其对卵母细胞成熟的影响尚不清楚。本研究的目的是了解翻译后修饰对PCOS妇女卵巢代谢稳态和卵母细胞发育潜力的潜在影响。采用质谱技术对PCOS组和对照组卵巢颗粒细胞乙酰化蛋白质组进行定量分析。有广泛的赖氨酸乙酰化的蛋白质，其中265个蛋白质的乙酰化水平增加，68个蛋白质的乙酰化水平降低PCOS组。最值得注意的是，差异乙酰化蛋白质显着丰富的代谢途径的糖酵解，脂肪酸降解，TCA循环，色氨酸代谢，支链氨基酸降解。乙酰辅酶A乙酰转移酶1（ACAT1）是这些代谢途径的核心酶，在PCOS组中乙酰化水平升高，PCOS颗粒细胞中ACAT1乙酰化水平与临床上的卵母细胞质量和胚胎发育效率呈负相关。PCOS颗粒细胞中关键酶的赖氨酸乙酰化改变可能减弱其活性，改变卵泡微环境的代谢稳态，促进卵母细胞成熟和胚胎发育。
Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders accompanied by obvious metabolic abnormalities. Lower-quality oocytes and embryos are often found in PCOS women during assisted reproductive technology treatment. However, there is still no clarity about the mechanism of ovarian metabolic disorders and the impact on oocyte maturation in PCOS. The aim of this study was to understand the potential effect of the posttranslational modification on ovarian metabolic homeostasis and oocyte development potential in women with PCOS. A quantitative analysis of acetylated proteomics in ovarian granulosa cells of PCOS and control groups was carried out by mass spectrometry. There was widespread lysine acetylation of proteins, of which 265 proteins had increased levels of acetylation and 68 proteins had decreased levels of acetylation in the PCOS group. Most notably, differentially acetylated proteins were significantly enriched in the metabolic pathways of glycolysis, fatty acid degradation, TCA cycle, tryptophan metabolism, and branched-chain amino acid degradation. Acetyl-CoA acetyltransferase 1 (ACAT1) was an enzyme central to these metabolic pathways with increased acetylation level in the PCOS group, and there was a negative correlation of ACAT1 acetylation levels in PCOS granulosa cells with oocyte quality and embryo development efficiency in the clinic. Lysine acetylation changes of key enzymes in PCOS granulosa cells might attenuate their activities and alter metabolic homeostasis of follicular microenvironment for oocyte maturation and embryo development.