Molecular Signatures Correlated With Poor IVF Outcomes: Insights From the mRNA and lncRNA Expression of Endometriotic Granulosa Cells.

Molecular Signatures Correlated With Poor IVF Outcomes: Insights From the mRNA and lncRNA Expression of Endometriotic Granulosa Cells.
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与 IVF 不良结果相关的分子特征:子宫内膜异位颗粒细胞 mRNA 和 lncRNA 表达的见解

DOI:
10.3389/fendo.2022.825934
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发表时间:
2022
影响因子:
5.2
通讯作者:
Zhang S
Zhang S
中科院分区:
医学2区
文献类型:
--
作者:
Shi L;Wei X;Wu B;Yuan C;Li C;Dai Y;Chen J;Zhou F;Lin X;Zhang S

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卵巢子宫内膜异位症妇女体外受精(IVF)的结果明显差于无卵巢子宫内膜异位症(OEM)的患者,如获得的卵母细胞较少。然而,确切的病理生理机制仍然是未知的。因此,我们进行了一项前瞻性研究,使用RNA测序方法分析了来自OEM导致卵母细胞回收较少的患者的颗粒细胞(GC)和来自男性因素(MF)不育症对照组的GC之间的mRNA和lncRNA转录组。我们发现了一组显著差异表达的基因(DEG),包括NR 5A 2、MAP 3 K5、PGRMC 2、PRKAR 2A、DEPTOR、ITGAV、KPNB 1、GPC 6、EIF 3A和SMC 5,这些基因被证实与OEM患者GC中获卵数呈负相关,而DUSP 1则相反。这些DEG的分子功能主要集中在涉及丝裂原活化蛋白激酶(MAPK)信号传导、Wnt信号传导、类固醇激素反应、凋亡和细胞连接的通路中。此外,我们进行了lncRNA分析,并确定了一组差异表达的已知/新的lncRNA,这些lncRNA与经验证的DEG共表达,并与回收的卵母细胞数量相关。在DEG和已知/新的lncRNA之间构建共表达网络。本研究中发现的这些独特的分子特征参与了OEM患者卵巢储备功能障碍的病理调节。
The outcomes of in vitro fertilization (IVF) for endometriotic women are significantly worse than for patients without ovarian endometriosis (OEM), as shown by fewer retrieved oocytes. However, the exact pathophysiological mechanism is still unknown. Thus, we conducted a prospective study that analyzed mRNA and lncRNA transcriptome between granulosa cells (GCs) from patients with fewer retrieved oocytes due to OEM and GCs from controls with male factor (MF) infertility using an RNA sequencing approach. We found a group of significantly differentially expressed genes (DEGs), including NR5A2, MAP3K5, PGRMC2, PRKAR2A, DEPTOR, ITGAV, KPNB1, GPC6, EIF3A, and SMC5, which were validated to be upregulated and negatively correlated with retrieved oocyte numbers in GCs of patients with OEM, while DUSP1 demonstrated the opposite. The molecular functions of these DEGs were mainly enriched in pathways involving mitogen-activated protein kinase (MAPK) signaling, Wnt signaling, steroid hormone response, apoptosis, and cell junction. Furthermore, we performed lncRNA analysis and identified a group of differentially expressed known/novel lncRNAs that were co-expressed with the validated DEGs and correlated with retrieved oocyte numbers. Co-expression networks were constructed between the DEGs and known/novel lncRNAs. These distinctive molecular signatures uncovered in this study are involved in the pathological regulation of ovarian reserve dysfunction in OEM patients.
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