Yerushalmi G M, Salmon-Divon M, Yung Y, Maman E, Kedem A, Ophir L, Elemento O, Coticchio G, Dal Canto M, Mignini Renzinu M, Fadini R, Hourvitz A
IVF Unit and Reproduction Lab, Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Department of Molecular Biology, Ariel University, Ariel, Israel.
Mol Hum Reprod. 2014 Aug;20(8):719-35. doi: 10.1093/molehr/gau031. Epub 2014 Apr 25.
Cumulus expansion and oocyte maturation are central processes in ovulation. Knowledge gained from rodent and other mammalian models has revealed some of the molecular pathways associated with these processes. However, the equivalent pathways in humans have not been thoroughly studied and remain unidentified. Compact cumulus cells (CCs) from germinal vesicle cumulus oocyte complexes (COCs) were obtained from patients undergoing in vitro maturation (IVM) procedures. Expanded CCs from metaphase 2 COC were obtained from patients undergoing IVF/ICSI. Global transcriptome profiles of the samples were obtained using state-of-the-art RNA sequencing techniques. We identified 1746 differentially expressed (DE) genes between compact and expanded CCs. Most of these genes were involved in cellular growth and proliferation, cellular movement, cell cycle, cell-to-cell signaling and interaction, extracellular matrix and steroidogenesis. Out of the DE genes, we found 89 long noncoding RNAs, of which 12 are encoded within introns of genes known to be involved in granulosa cell processes. This suggests that unique noncoding RNA transcripts may contribute to the regulation of cumulus expansion and oocyte maturation. Using global transcriptome sequencing, we were able to generate a library of genes regulated during cumulus expansion and oocyte maturation processes. Analysis of these genes allowed us to identify important new genes and noncoding RNAs potentially involved in COC maturation and cumulus expansion. These results may increase our understanding of the process of oocyte maturation and could ultimately improve the efficacy of IVM treatment.
卵丘扩展和卵母细胞成熟是排卵过程中的核心环节。从啮齿动物和其他哺乳动物模型中获得的知识揭示了一些与这些过程相关的分子途径。然而,人类中的等效途径尚未得到充分研究,仍然不明。从接受体外成熟(IVM)程序的患者中获取来自生发泡卵丘卵母细胞复合体(COC)的致密卵丘细胞(CC)。从接受体外受精/卵胞浆内单精子注射(IVF/ICSI)的患者中获取来自中期2 COC的扩展CC。使用最先进的RNA测序技术获得样本的整体转录组图谱。我们鉴定出致密CC和扩展CC之间有1746个差异表达(DE)基因。这些基因大多参与细胞生长和增殖、细胞运动、细胞周期、细胞间信号传导和相互作用、细胞外基质和类固醇生成。在这些DE基因中,我们发现了89个长链非编码RNA(lncRNA),其中12个在已知参与颗粒细胞过程的基因的内含子中编码。这表明独特的非编码RNA转录本可能有助于调节卵丘扩展和卵母细胞成熟。通过整体转录组测序,我们能够生成一个在卵丘扩展和卵母细胞成熟过程中受调控的基因文库。对这些基因的分析使我们能够鉴定出可能参与COC成熟和卵丘扩展的重要新基因和非编码RNA。这些结果可能会增进我们对卵母细胞成熟过程的理解,并最终提高IVM治疗的疗效。