Center for Reproductive Medicine, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, China.
Binhai Hospital of Tianjin Medical University General Hospital, Tianjin 300480, China.
Gene. 2019 Feb 20;686:250-260. doi: 10.1016/j.gene.2018.11.025. Epub 2018 Nov 17.
This study aimed to determine the microRNA (miRNA) profiles in granulosa cells (GCs) from the follicular fluid (FF) of patients with varying levels of ovarian reserve function. We included 45 women undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment. After collecting GCs from each patient, total RNA was extracted from 12 samples. Using Illumina/deep-sequencing technology, we analyzed the small RNAs in each group. Using the R package, we identified the differentially expressed (DE) miRNAs among patients with varying levels of ovarian reserve function. We identified 20 conserved and 3 novel miRNAs that were upregulated in the poor ovarian response (POR) group and 30 conserved miRNAs and 1 novel miRNA that were upregulated in the polycystic ovary syndrome (PCOS) group. Bioinformatics analysis revealed complementary pairing between miR-23a and the 3'-untranslated region (UTR) of the Sirt1 mRNA. miR-23a can regulate SIRT1 protein expression at the posttranscriptional level in GCs. Overexpressing miR-23a can inhibit the expression of SIRT1, decrease the stimulatory effect of SIRT1 on the ERK1/2 pathway, inhibit the expression of p-ERK1/2, and increase apoptosis in GCs. Previous studies confirmed that miR-23a targets SIRT1 and promotes apoptosis in GCs by inhibiting the ERK1/2 signaling pathway. This study provides a novel perspective regarding the role of miRNAs in the regulation of human GC apoptosis in vitro.
本研究旨在确定不同卵巢储备功能患者卵泡液(FF)中的颗粒细胞(GC)中的 microRNA(miRNA)谱。我们纳入了 45 名接受体外受精(IVF)和胞浆内精子注射(ICSI)治疗的女性。从每位患者采集 GC 后,从 12 个样本中提取总 RNA。使用 Illumina/深度测序技术,我们分析了每组的小 RNA。使用 R 包,我们鉴定了卵巢储备功能不同患者之间差异表达(DE)的 miRNAs。我们鉴定了在卵巢反应不良(POR)组中上调的 20 个保守和 3 个新的 miRNA,以及在多囊卵巢综合征(PCOS)组中上调的 30 个保守 miRNA 和 1 个新的 miRNA。生物信息学分析揭示了 miR-23a 与 Sirt1 mRNA 3'-非翻译区(UTR)之间的互补配对。miR-23a 可以在 GC 中在转录后水平调节 SIRT1 蛋白表达。过表达 miR-23a 可以抑制 SIRT1 的表达,降低 SIRT1 对 ERK1/2 途径的刺激作用,抑制 p-ERK1/2 的表达,并增加 GC 中的细胞凋亡。先前的研究证实,miR-23a 通过抑制 ERK1/2 信号通路靶向 SIRT1 并促进 GC 中的细胞凋亡。本研究为 miRNA 在体外调节人 GC 细胞凋亡中的作用提供了新的视角。