RNA-sequencing reveals novel molecular mechanisms of endometriosis lesion development in a mouse model

Our understanding of molecular mechanisms contributing to the pathophysiology of endometriosis, and their upstream regulators, remains limited. Using a C57Bl/6 mouse model of endometriosis in which decidualized endometrial tissue fragments are transferred to subcutaneous sites in recipient mice to mimic endometriosis lesions, we have generated a comprehensive profile of gene expression in decidualized endometrial tissue (n=4), and endometriosis-like lesions at Day 7 (n=4) and Day 14 (n=4) of lesion formation. High throughput mRNA sequencing allowed identification of genes and pathways involved in the initiation and progression of endometriosis-like lesions. We found distinct patterns of gene expression with substantial differences between the lesions and the decidualized endometrium from which they arose, but no differentially expressed genes between the two lesion timepoints. The transcriptional changes at the outset of lesion formation indicated substantial upregulation of immune response-associated canonical pathways. Pathway enrichment analysis indicates multiple potential endogenous upstream regulators, and reveals multiple gene candidates not previously implicated in endometriosis lesion formation suggesting these mediators may have novel roles in disease progression. Collectively, the provided data will be a valuable resource to inform research on the molecular mechanisms contributing to endometriosis development. We performed gene expression profiling using RNA-seq of donor decidualized endometrium (n=4), endometriosis-like lesions at Day 7 (n=4) and Day 14 (n=4) in a C57BL/6 subcutaneous mouse model of endometriosis. There are two additional experimental groups (miR-155 deficient and miR-223 deficient mouse models) also included in this dataset giving a total of 36 samples (4 biological replicates at each timepoint, 12 samples per genotype) These additional samples will reported in a separate manuscript to elucidate the impact of microRNA modulation in endometriosis-like lesion development in mice.

目前我们对子宫内膜异位症（endometriosis）病理生理过程及其上游调控因子的分子机制的认知仍十分有限。本研究采用C57BL/6小鼠子宫内膜异位症模型，将蜕膜化子宫内膜组织片段移植至受体小鼠皮下部位以模拟子宫内膜异位症病灶，分别对供体蜕膜化子宫内膜组织（n=4）、病灶形成第7天（n=4）及第14天（n=4）的类子宫内膜异位症病灶开展了全面的基因表达谱分析。借助高通量mRNA测序（high throughput mRNA sequencing），我们鉴定出参与类子宫内膜异位症病灶起始与进展的基因及通路。研究发现，病灶与其起源的蜕膜化子宫内膜组织间存在截然不同的基因表达模式，二者差异显著；但两个病灶时间点之间未检测到差异表达基因（differentially expressed genes）。病灶形成初期的转录变化（transcriptional changes）显示，免疫应答相关经典通路出现显著上调。通路富集分析（pathway enrichment analysis）结果表明存在多种潜在内源性上游调控因子，同时鉴定出此前未被关联至子宫内膜异位症病灶形成的多个候选基因，提示这些介导因子可能在疾病进展中发挥全新作用。综上，本数据集将为阐明子宫内膜异位症发生发展的分子机制提供极具价值的研究资源。本研究通过RNA测序（RNA-seq）对C57BL/6小鼠皮下子宫内膜异位症模型中的供体蜕膜化子宫内膜组织（n=4）、第7天（n=4）及第14天（n=4）的类子宫内膜异位症病灶完成了基因表达谱分析。本数据集还包含另外两个实验组：miR-155缺陷型与miR-223缺陷型小鼠模型，总计36个样本（每个时间点含4个生物学重复，每种基因型含12个样本）。上述额外样本的相关研究将以单独稿件发表，旨在阐明微小RNA（microRNA）调控对小鼠类子宫内膜异位症病灶发育的影响。