Macklon Nick S, van der Gaast Mark H, Hamilton Amy, Fauser Bart C J M, Giudice Linda C
Department of Reproductive Medicine and Gynecology, University Medical Center, Utrecht, Netherlands.
Reprod Sci. 2008 Apr;15(4):357-65. doi: 10.1177/1933719107311781.
The aim of this prospective paired cohort study is to elucidate the impact of ovarian stimulation with recombinant follicle-stimulating hormone in combination with gonadotropin-releasing hormone antagonist on the endometrial transcriptome. Oocyte donors underwent endometrial biopsy during the implantation window of the nonstimulated cycle and following ovarian stimulation with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonist but no luteal progesterone supplementation (n = 4). Microarray analysis showed 142 genes to be significantly upregulated and 98 significantly downregulated. Significantly upregulated genes included those sequencing for the chemokine ligand CXCL 13, the Dickkopf homolog, steroidogenic acute regulatory protein, and homeobox C6. Also upregulated were genes inhibited by progesterone, such as insulin-like growth factor binding protein 5. In conclusion, ovarian stimulation with follicle-stimulating hormone and gonadotropin-releasing hormone antagonist dysregulates the expression of many genes involved in cell adhesion, T-cell receptor signaling, and regulation of signal transduction. These data suggest that dysregulation of the endometrial transcriptome in the stimulated cycle is not fully attributable to supraphysiological sex steroid levels at the folliculo-luteal transition.
这项前瞻性配对队列研究的目的是阐明重组促卵泡激素联合促性腺激素释放激素拮抗剂进行卵巢刺激对子宫内膜转录组的影响。卵母细胞捐赠者在未刺激周期的植入窗期间以及在接受重组促卵泡激素和促性腺激素释放激素拮抗剂进行卵巢刺激但未补充黄体期孕酮后进行了子宫内膜活检（n = 4）。微阵列分析显示142个基因显著上调，98个基因显著下调。显著上调的基因包括趋化因子配体CXCL 13、Dickkopf同源物、类固醇生成急性调节蛋白和同源盒C6的测序基因。受孕酮抑制的基因，如胰岛素样生长因子结合蛋白5也上调。总之，促卵泡激素和促性腺激素释放激素拮抗剂进行卵巢刺激会使许多参与细胞黏附、T细胞受体信号传导和信号转导调节的基因表达失调。这些数据表明，刺激周期中子宫内膜转录组的失调并不完全归因于卵泡期-黄体期过渡时超生理水平的性类固醇。
