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. Overall design: 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.