The transcriptomic analysis of equine in vitro cultured fibroblasts derived from endometria with or without endometrosis.

Abstract

Endometrosis is a chronic degenerative condition of the endometrium in the mare, with fibrosis being the most prevalent. In the current study, the transcriptome signature of in vitro cultured fibroblasts derived from endometria with or without endometrosis was compared by RNA sequencing to elucidate alterations in gene expression that lead to dysregulated cellular function and the underlying molecular mechanisms driving fibrosis. A total of 191 genes were identified as altered, including 43 up-regulated and 148 down-regulated. In addition, the differentially expressed genes (DEGs) were annotated to nine KEGG pathways and almost 280 Gene Ontology (GO) terms. The DEGs classified as belonging to the biological process category were annotated with terms including extracellular matrix (ECM) organization, wound healing, and regulation of the innate immune response. The DEGs classified as 'molecular function' were annotated with terms including collagen binding, metaloendopeptidase activity, L-ascorbic acid binding, and fibroblast growth factor. Moreover, DEGs were assigned to KEGG pathways, including ECM-receptor interaction, transcriptional misregulation in cancer, focal adhesion, and others. The results showed that the transcriptomic profile of fibrotic fibroblasts was altered in comparison to non-fibrotic fibroblasts, which consequently could affect their function. The gene profile of enzymes responsible for ECM remodelling was downregulated, indicating that the excessive ECM deposition in the fibrotic process cannot be degraded. The expression of immune-related genes differed between fibrotic and non-fibrotic fibroblasts, suggesting that fibroblasts from fibrotic endometrium may be more active in modulating immune responses, which play a crucial role in the development of fibrosis.