Follicle Biology Laboratory, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Hum Reprod. 2011 May;26(5):1035-51. doi: 10.1093/humrep/der036. Epub 2011 Mar 3.
Cumulus cell (CC) gene expression is suggested as a non-invasive analysis method to predict oocyte competence. There are, however, important between-patient differences in CC gene expression. These can be compensated when expression results are combined with patient and cycle characteristics using a multiple regression analysis model.
From ICSI patients stimulated with GnRH antagonist and recombinant FSH (n= 25) or GnRH agonist and highly purified menotrophin (n= 20), CC were collected and oocytes were individually fertilized and cultured. CC were analyzed for the expression of Syndecan 4 (SDC4), Prostaglandin-endoperoxide synthase 2 (PTGS2), Versican (VCAN), Activated leukocyte cell adhesion molecule, Gremlin 1, transient receptor potential cation channel, subfamily M, member 7 (TRPM7), Calmodulin 2 and Inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) using quantitative PCR. Results were analyzed in relation to the stimulation protocol. Within-patient variation in gene expression was related to oocyte maturity and developmental potential. Models predictive for normal embryo or blastocyst development and pregnancy in single embryo transfer cycles were developed.
Mature oocytes have higher PTGS2 and lower VCAN expression in their cumulus. All genes except VCAN had a positive correlation with good embryo or blastocyst morphology and were used to develop predictive models for embryo or blastocyst development (P< 0.01). Specific models were obtained for the two stimulation protocols. In both groups, better cleavage-stage embryo prediction relied on TRPM7 and ITPKA expression and pregnancy prediction relied on SDC4 and VCAN expression. In the current data set, the use of CC expression for pregnancy prediction resulted in a sensitivity of >70% and a specificity of >90%.
Multivariable models based on CC gene expression can be used to predict embryo development and pregnancy.
卵丘细胞（CC）的基因表达被认为是一种非侵入性的分析方法，可用于预测卵母细胞的能力。然而，CC 基因表达在患者之间存在重要差异。当使用多元回归分析模型将表达结果与患者和周期特征相结合时，可以补偿这些差异。
从接受 GnRH 拮抗剂和重组 FSH 刺激的 ICSI 患者（n=25）或 GnRH 激动剂和高纯度促性腺激素刺激的患者（n=20）中收集 CC，并对单个卵母细胞进行受精和培养。使用定量 PCR 分析 CC 中 Syndecan 4（SDC4）、前列腺素内过氧化物合酶 2（PTGS2）、Versican（VCAN）、活化白细胞细胞黏附分子、Gremlin 1、瞬时受体电位阳离子通道亚家族 M 成员 7（TRPM7）、钙调蛋白 2 和肌醇 1,4,5-三磷酸 3-激酶 A（ITPKA）的表达。结果与刺激方案相关。个体内基因表达的变异性与卵母细胞成熟度和发育潜能有关。在单胚胎转移周期中，建立了预测正常胚胎或胚泡发育和妊娠的模型。
成熟卵母细胞的卵丘中 PTGS2 表达较高，VCAN 表达较低。除了 VCAN 之外，所有基因都与良好的胚胎或胚泡形态呈正相关，并被用于开发预测胚胎或胚泡发育的模型（P<0.01）。为两种刺激方案获得了特定的模型。在两组中，更好的卵裂期胚胎预测依赖于 TRPM7 和 ITPKA 的表达，而妊娠预测则依赖于 SDC4 和 VCAN 的表达。在当前数据集，使用 CC 表达进行妊娠预测的敏感性>70%，特异性>90%。
基于 CC 基因表达的多变量模型可用于预测胚胎发育和妊娠。
