NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), PO Box 510600, Guangzhou, China.
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, PO Box 510623, Guangzhou, China.
Genes Genomics. 2024 Jul;46(7):803-815. doi: 10.1007/s13258-024-01497-8. Epub 2024 May 22.
Patients of ovary endometriosis have an abnormal immune micro-environment, leading to endometrial tissue that from retrograde menstruation evade immune surveillance and subsequently develop into ectopic lesions.
This study aims to elucidate the crucial immune cells and molecular pathways that are associated with an aberrant immune micro-environment of endometriosis.
In this study, we identified differentially expressed genes between ovarian ectopic endometrial tissue (OVE) and eutopic endometrial tissue from patients with endometriosis (PE) and non-endometriosis patients (CON) by analyzing the mRNA sequencing data. Additionally, we used WGCNA(Weighted Gene Co-expression Network Analysis) to screen for key genes related to immune cell infiltration and compared the sub-types of infiltrating immune cells using CIBERSORT(cell-type identification by estimating relative subsets of RNA transcript). Subsequently, we conducted a single-cell analysis on the identified key genes. Furthermore, we analyzed potential drugs suitable for ovarian endometriosis treatment using pRRophertic.
Seven key genes associated with immune cell infiltration were screened out. The expression of these genes in OVE was significantly lower than that in PE and CON. These key genes were mainly enriched in the NK cell-mediated cytotoxicity pathway, especially for CD16 + CD56dim NK. Moreover, NK cells infiltration in ovarian endometriosis was significantly reduced compared with PE and CON, while M2 macrophage shown the opposite. Results of the single-cell analysis showed that the expression of the seven key genes in NK cells and monocyte-macrophages in OVE was significantly lower than that in PE or CON. Additionally, we identified potential drugs suitable for ovarian endometriosis treatment.
The decreased infiltration of NK cells and increased infiltration of M2 macrophages contribute to the evasion of immune surveillance against endometrial tissue, promoting the progression of OVE. Therefore, potential strategies for the treatment of OVE include increasing NK cell activation and decreasing M2 macrophage polarization.
卵巢子宫内膜异位症患者存在异常的免疫微环境，导致子宫内膜组织经逆行月经逃避免疫监视，随后发展为异位病变。
本研究旨在阐明与子宫内膜异位症异常免疫微环境相关的关键免疫细胞和分子途径。
通过分析卵巢异位子宫内膜组织（OVE）和子宫内膜异位症患者（PE）与非子宫内膜异位症患者（CON）的 mRNA 测序数据，本研究鉴定了卵巢异位内膜组织（OVE）和子宫内膜异位症患者（PE）与非子宫内膜异位症患者（CON）之间差异表达的基因。此外，我们使用 WGCNA（加权基因共表达网络分析）筛选与免疫细胞浸润相关的关键基因，并使用 CIBERSORT（通过估计 RNA 转录物的相对亚群来鉴定细胞类型）比较浸润免疫细胞的亚群。随后，我们对鉴定出的关键基因进行单细胞分析。此外，我们使用 pRRophertic 分析了适合卵巢子宫内膜异位症治疗的潜在药物。
筛选出与免疫细胞浸润相关的 7 个关键基因。这些基因在 OVE 中的表达明显低于 PE 和 CON。这些关键基因主要富集在 NK 细胞介导的细胞毒性途径中，特别是 CD16+CD56dim NK。此外，与 PE 和 CON 相比，卵巢子宫内膜异位症中 NK 细胞浸润明显减少，而 M2 巨噬细胞则相反。单细胞分析结果表明，在 OVE 中 NK 细胞和单核细胞-巨噬细胞中 7 个关键基因的表达明显低于 PE 或 CON。此外，我们还确定了适合卵巢子宫内膜异位症治疗的潜在药物。
NK 细胞浸润减少和 M2 巨噬细胞浸润增加导致对子宫内膜组织的免疫监视逃避，促进 OVE 的进展。因此，治疗 OVE 的潜在策略包括增加 NK 细胞的激活和减少 M2 巨噬细胞的极化。
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