Cumulus cell acetyl-CoA metabolism from acetate is associated with maternal age but only partially with oocyte maturity.
Cumulus cell acetyl-CoA metabolism from acetate is associated with maternal age but only partially with oocyte maturity.
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DOI：
10.1080/19396368.2021.2003479
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发表时间：
2022-03
影响因子：
2.4
通讯作者：
Snyder NW
中科院分区：
文献类型：
--
作者：
Anderson S;Xu P;Frey AJ;Goodspeed JR;Doan MT;Orris JJ;Clements N;Glassner MJ;Snyder NW
与卵母细胞结合的卵丘细胞（CC）团块为卵母细胞提供生长和信号因子。因此，CC的代谢可能会影响卵母细胞的功能，CC代谢可能是体外受精卵母细胞能力的预测。CC被认为是高度糖酵解的，但在人类中缺乏使用其他潜在碳底物的数据。这项前瞻性盲态队列研究旨在通过年龄和卵母细胞能力检查CC的底物利用率。在卵母细胞取出程序后，从参与者中取出单独的CC团块，与稳定同位素标记的底物一起孵育，并使用液相色谱-高分辨率质谱法（LC-HRMS）分析主要代谢中间体（包括乙酰辅酶A）的同位素富集。乙酰辅酶A的酰基链含有2个碳，其可以衍生自13 C标记的底物，产生含有2个13 C原子的M+2同位素体。比较三种主要碳源的命运，M+2乙酰辅酶A的平均富集（平均值，标准差）为葡萄糖（3.6，7.7），谷氨酰胺（9.4，6.2）和乙酸（20.7，13.9）。由于这种来自乙酸盐的意想不到的高和可变标记，我们随后检查了来自21名≤34岁女性的278个CC（49.06，12.73）中的乙酰辅酶A平均%富集，与来自10名>34岁女性的124个CC（43.48，16.20）相比，乙酸盐的乙酰辅酶A平均%富集随年龄降低（p=0.0004，t检验）。与中期I和中期II卵母细胞相关的CC相比，与未成熟前期I卵母细胞相关的CC在M+2乙酰辅酶A中的富集显著较低（差异：-6.02，CI：-1.74，-13.79，p=0.013）。单个CC团块中的乙酸代谢与卵母细胞成熟度呈正相关，并随母亲年龄的增加而降低。这些发现表明，CC代谢的非葡萄糖底物应调查相对于卵母细胞功能和年龄相关的生育能力。
Cumulus cell (CC) clumps that associate with oocytes provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function, and CC metabolism may be predictive of oocyte competence for in vitro fertilization. CCs are thought to be highly glycolytic, but data on the use of other potential carbon substrates are lacking in humans. This prospective and blinded cohort study was designed to examine the substrate utilization of CCs by age and oocyte competence. Individual sets of CC clumps from participants were removed after oocyte retrieval procedure, incubated with stable isotope labeled substrates, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA. The acyl-chain of acetyl-CoA contains 2 carbons that can be derived from 13C-labeled substrates resulting in an M+2 isotopologue that contains 2 13C atoms. Comparing the fate of three major carbon sources, mean enrichment of M+2 acetyl-CoA (mean, standard deviation) was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Due to this unexpected high and variable labeling from acetate, we then examined acetyl-CoA mean % enrichment from acetate of in 278 CCs from 21 women ≤34 (49.06, 12.73) decreased with age compared to 124 CCs from 10 women >34 (43.48, 16.20) (p=0.0004, t-test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M+2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: −6.02, CI: −1.74,−13.79, p=0.013). Acetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of non-glucose substrates should be investigated relative to oocyte function and age-related fertility.
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影响因子：
6.7
作者：
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通讯作者：
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