Ovarian reserve status in young women is associated with altered gene expression in membrana granulosa cells
Ovarian reserve status in young women is associated with altered gene expression in membrana granulosa cells
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DOI：
10.1093/molehr/gas008
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发表时间：
2012-07-01
影响因子：
4
通讯作者：
Racowsky, Catherine
中科院分区：
文献类型：
--
作者：
Skiadas, Christine C.;Duan, Shenghua;Racowsky, Catherine
卵巢储备减少（DOR）是不孕症的一个具有挑战性的诊断，因为目前还没有测试来预测谁可能会受到这种情况的影响，或者在什么年龄。我们设计了本研究，以比较基因表达谱的膜颗粒细胞从年轻女性受DOR与那些从卵子捐赠者的年龄相仿，并确定是否可以确定不同的遗传模式，以提供深入了解DOR的病因。根据FSH水平以及IVF周期中卵泡发育不良确定DOR的年轻女性（n 13）。正常卵巢储备（NOR）的卵子捐赠者组成对照组（n 13）。取卵后收集颗粒细胞，提取RNA并进行微阵列分析以评估组间的遗传差异。采用定量RTPCR（qRTPCR）进行了验证性研究。在DOR患者和卵子供体之间观察到基因表达的多个显著差异。采用qRT-PCR方法进一步检测抗苗勒管激素（anti-Mullerian hormone，AMH）和促黄体生成激素受体（luteinizing hormone receptor，LHCGR）基因的表达。AMH的平均表达在卵子捐赠者中显著更高（校正的P值0.01），LHCGR的平均表达在DOR患者中显著更高（校正的P值0.005）。在由5名NOR和5名DOR患者组成的组中验证了4个额外基因的表达水平，即孕酮受体膜组分2（PGRMC 2）、前列腺素E受体3（亚型EP 3）（PTGER 3）、类固醇生成急性调节蛋白（星星）和StAR相关脂质转移结构域4（StarD 4）。我们的结论是，基因表达分析有很大的潜力，以确定哪些年轻女性可能受到DOR。更重要的是，我们的分析表明，DOR患者根据基因表达谱分为两个不同的亚组，表明在这种病理的发展过程中可能涉及不同的机制。
Diminished ovarian reserve (DOR) is a challenging diagnosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. We designed the present study to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from egg donors of similar age and to determine if distinct genetic patterns could be identified to provide insight into the etiology of DOR. Young women with DOR were identified based on FSH level in conjunction with poor follicular development during an IVF cycle (n 13). Egg donors with normal ovarian reserve (NOR) comprised the control group (n 13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic differences between the groups. Confirmatory studies were undertaken with quantitative RTPCR (qRTPCR). Multiple significant differences in gene expression were observed between the DOR patients and egg donors. Two genes linked with ovarian function, anti-Mullerian hormone (AMH) and luteinizing hormone receptor (LHCGR), were further analyzed with qRTPCR in all patients. The average expression of AMH was significantly higher in egg donors (adjusted P-value 0.01), and the average expression of LHCGR was significantly higher in DOR patients (adjusted P-value 0.005). Expression levels for four additional genes, progesterone receptor membrane component 2 (PGRMC2), prostaglandin E receptor 3 (subtype EP3) (PTGER3), steroidogenic acute regulatory protein (StAR), and StAR-related lipid transfer domain containing 4 (StarD4), were validated in a group consisting of five NOR and five DOR patients. We conclude that gene expression analysis has substantial potential to determine which young women may be affected with DOR. More importantly, our analysis suggests that DOR patients fall into two distinct subgroups based on gene expression profiles, indicating that different mechanisms may be involved during development of this pathology.