与 IVF 不良结局相关的分子特征:来自子宫内膜异位症颗粒细胞的 mRNA 和 lncRNA 表达的见解。

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

机构信息

Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, China.

International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.

出版信息

Front Endocrinol (Lausanne). 2022 Feb 28;13:825934. doi: 10.3389/fendo.2022.825934. eCollection 2022.

Abstract

The outcomes of 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 , , , , , , , , , and , which were validated to be upregulated and negatively correlated with retrieved oocyte numbers in GCs of patients with OEM, while 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.

摘要

内异症患者的受精(IVF)结局明显差于非卵巢子宫内膜异位症(OEM)患者,表现为获卵数减少。然而,确切的病理生理机制仍不清楚。因此,我们进行了一项前瞻性研究,使用 RNA 测序方法分析了由于 OEM 导致获卵数减少的患者的颗粒细胞(GC)和男性因素(MF)不孕患者的 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(DEGs),包括、、、、、、、和,这些基因在 OEM 患者的 GC 中上调且与获卵数呈负相关,而则相反。这些 DEGs 的分子功能主要富集在涉及丝裂原激活蛋白激酶(MAPK)信号、Wnt 信号、甾体激素反应、细胞凋亡和细胞连接的途径中。此外,我们进行了 lncRNA 分析,鉴定了一组差异表达的已知/新型 lncRNAs,这些 lncRNAs与验证的 DEGs 共表达并与获卵数相关。构建了 DEGs 和已知/新型 lncRNA 之间的共表达网络。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/868a/8919698/ce9d8eaaa2cf/fendo-13-825934-g001.jpg

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