Human follicular fluid proteome reveals association between overweight status and oocyte maturation abnormality
Human follicular fluid proteome reveals association between overweight status and oocyte maturation abnormality
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人类卵泡液蛋白质组揭示超重状态与卵母细胞成熟异常之间的关联
DOI：
10.1186/s12014-020-09286-7
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发表时间：
2020-06-08
影响因子：
3.8
通讯作者：
Liu, Fujun
中科院分区：
文献类型：
--
作者：
Liu, Xin;Wang, Yanhua;Liu, Fujun
研究背景人卵泡液（HFF）由卵泡发育所需的必需蛋白质组成，为卵母细胞的成熟提供了重要的微环境。最近，超重状态已被认为是卵母细胞成熟的不利影响因素，但 HFF 蛋白质组是否可以为评估基于超重的卵母细胞成熟缺陷提供蛋白质标记仍不清楚。方法为了揭示与卵母细胞成熟异常相关的基于 HFF 的分子特征，进行了基于 iTRAQ 的比较蛋白质组分析，以研究正常体重女性和超重状态女性的不同 HFF 蛋白表达谱。结果我们的数据中对 200 个 HFF 蛋白进行了定量，其中 43% 与之前的两份出版物没有重叠。与正常体重女性的HFF蛋白相比，超重女性的HFF蛋白有22个上调和21个下调。 PANTHER数据库显示这些改变的HFF蛋白参与发育、代谢、免疫和凝血，STRING数据库显示了它们复杂的相互作用网络。通过 WAP 四二硫键核心结构域蛋白 2 (WFDC2)、乳转铁蛋白 (LTF)、前列腺特异性抗原 (KLK3)、纤连蛋白 (FN1) 和甘油醛 3-磷酸脱氢酶 (GAPDH) 的蛋白质印迹分析验证了蛋白质组结果的置信度。此外，ELISA 测定表明 WFDC2 可能是诊断超重状态引起的卵母细胞成熟停滞的潜在有用候选 HFF 标记。结论我们的工作提供了一个涉及卵母细胞成熟的新的补充高置信度 HFF 数据集，这些改变的 HFF 蛋白可能对超重状态女性卵母细胞成熟异常具有临床相关性以及诊断和预后价值。
BackgroundHuman follicular fluid (HFF), which is composed by essential proteins required for the follicle development, provides an important microenvironment for oocyte maturation. Recently, overweight status has been considered as a detrimental impact factor on oocyte maturation, but whether HFF proteome could provide protein markers for assessing overweight-based oocyte maturation deficiency is still unknown.MethodsTo reveal the HFF-based molecular characteristics associated with abnormal oocyte maturation, an iTRAQ-based comparative proteomic analysis was performed to investigate different HFF protein expression profiles from normal weight women and overweight status women.ResultsTwo hundred HFF proteins were quantified in our data, of which 43% have not been overlapped by two previous publications. Compared with the HFF proteins of normal weight women, 22 up-regulated HFF proteins and 21 down-regulated HFF proteins were found in the overweight status women. PANTHER database showed these altered HFF proteins participated in development, metabolism, immunity, and coagulation, and STRING database demonstrated their complicated interaction networks. The confidence of proteomic outcome was verified by Western blot analysis of WAP four-disulfide core domain protein 2 (WFDC2), lactotransferrin (LTF), prostate-specific antigen (KLK3), fibronectin (FN1), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Further, ELISA assay indicated WFDC2 might be a potentially useful candidate HFF marker for the diagnosis of oocyte maturation arrest caused by overweight status.ConclusionsOur work provided a new complementary high-confidence HFF dataset involved in oocyte maturation, and these altered HFF proteins might have clinical relevance and diagnostic and prognostic value for abnormal oocyte maturation in overweight status women.