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卵巢过度刺激后卵泡液中的蛋白质和类固醇谱作为 IVF 结局的潜在生物标志物。

Protein and steroid profiles in follicular fluid after ovarian hyperstimulation as potential biomarkers of IVF outcome.

机构信息

ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah 84108, United States.

出版信息

J Proteome Res. 2012 Oct 5;11(10):5090-100. doi: 10.1021/pr300535g. Epub 2012 Sep 18.

Abstract

Controlled ovarian hyperstimulation is performed to assist with generation of multiple mature oocytes for use in in vitro fertilization (IVF). The goal of our study was to evaluate differences in protein and steroid profiles in ovarian follicular fluid (hFF) samples obtained during oocyte retrieval from women undergoing IVF treatment and to identify physiological pathways associated with the proteins. The hFF samples were depleted of abundant proteins, fractionated by ultrafiltration, digested, and analyzed by nano-LC-QTOF. Concentrations of 15 endogenous steroids were determined in the samples using LC-MS/MS methods. The total number of proteins identified in the samples was 75, of which 4, 7, and 2 were unique to the samples from women with viable pregnancy, miscarriage, and no pregnancy, respectively. Identified proteins were associated with the acute response signaling, coagulation system, intrinsic and extrinsic prothrombin activation, complement system, neuroprotective role of THOP1, FXR/RXR activation, role of tissue factor, and growth hormone pathways. A greater number of proteins associated with biosynthesis was found in hFF samples corresponding to the oocytes resulting in pregnancy. The abundance of seven proteins was found to be associated with steroidogenesis. The obtained data will contribute to better understanding of the pathogenesis and development of noninvasive markers for assessment of oocytes viability.

摘要

控制性卵巢超刺激是为了帮助生成多个成熟的卵母细胞,用于体外受精 (IVF)。我们的研究目的是评估在接受 IVF 治疗的女性取卵过程中获得的卵巢卵泡液 (hFF) 样本中的蛋白质和类固醇谱的差异,并确定与蛋白质相关的生理途径。hFF 样本中丰富的蛋白质被去除,用超滤法进行分级,然后消化,用纳升液相色谱-QTOF 进行分析。采用 LC-MS/MS 方法测定样本中 15 种内源性类固醇的浓度。在这些样本中鉴定出的蛋白质总数为 75 种,其中 4、7 和 2 种分别是有生育能力妊娠、流产和无妊娠的女性样本所特有的。鉴定出的蛋白质与急性反应信号、凝血系统、内源性和外源性凝血酶原激活、补体系统、THOP1 的神经保护作用、FXR/RXR 激活、组织因子的作用和生长激素途径有关。与导致妊娠的卵母细胞相对应的 hFF 样本中发现了更多与生物合成相关的蛋白质。发现 7 种蛋白质的丰度与类固醇生成有关。所得数据将有助于更好地理解非侵袭性标志物用于评估卵母细胞活力的发病机制和发展。

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