Burney Richard O, Talbi Said, Hamilton Amy E, Vo Kim Chi, Nyegaard Mette, Nezhat Camran R, Lessey Bruce A, Giudice Linda C
Department of Obstetrics and Gynecology, Stanford University, Stanford, California 94305, USA.
Endocrinology. 2007 Aug;148(8):3814-26. doi: 10.1210/en.2006-1692. Epub 2007 May 17.
The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.
识别子宫内膜异位症女性子宫内膜中的分子差异，是理解该疾病发病机制以及开发治疗相关不孕症和疼痛新策略的重要一步。在本研究中，我们对患有和未患有中度/重度子宫内膜异位症的女性的子宫内膜进行了全基因表达分析，并比较了月经周期各阶段的基因表达特征。转录组分析揭示了子宫内膜异位症女性子宫内膜从增殖期到分泌期转变的分子失调。对在分泌期早期获得的子宫内膜标本进行的平行基因表达分析表明，在子宫内膜异位症情况下，细胞存活增强以及参与DNA合成和细胞有丝分裂的基因持续表达。分泌期子宫内膜中孕酮调节基因的比较基因表达分析证实了孕酮反应减弱的观察结果。此外，还鉴定出了可能与该疾病相关的有趣候选易感基因，包括FOXO1A、MIG6和CYP26A1。这些发现共同为进一步研究子宫内膜异位症女性子宫内膜中孕酮反应减弱的因果关系和机制提供了框架。
