Transcriptomic profiling of mare endometrium at different stages of endometrosis

• Published in: Scientific reports Vol. 13; no. 1; p. 16263
• Main Authors: Szóstek-Mioduchowska, A., Wójtowicz, A., Sadowska, A., Moza Jalali, B., Słyszewska, M., Łukasik, K., Gurgul, A., Szmatoła, T., Bugno-Poniewierska, M., Ferreira-Dias, G., Skarzynski, D. J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.09.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337; 631/443/494; ADAMTS-1 protein; Connective tissues; Cytokines; Endometrium; Fibroblasts; Fibrosis; Homeostasis; Humanities and Social Sciences; Inflammation; Interleukin 13; Interleukin 17; Metabolism; multidisciplinary; Science; Science (multidisciplinary); Transcriptomes; Transcriptomics; Transforming growth factor-b1; Wound healing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-43359-5

In the current study, transcriptome profiles of mare  endometrium , classified into categories I, IIA, and IIB according to Kenney and Doig, were compared using RNA sequencing, analyzed, and functionally annotated using in silico analysis. In the mild stage (IIA) of endometrosis compared to category I  endometrium , differentially expressed genes (DEGs) were annotated to inflammation, abnormal metabolism, wound healing, and quantity of connective tissue. In the moderate stage (IIB) of endometrosis compared to category I  endometrium , DEGs were annotated to inflammation, fibrosis, cellular homeostasis, mitochondrial dysfunction, and pregnancy disorders. Ingenuity pathway analysis (IPA) identified cytokines such as transforming growth factor (TGF)-β1, interleukin (IL)-4, IL-13, and IL-17 as upstream regulators of DEGs associated with cellular homeostasis, metabolism, and fibrosis signaling pathways. In vitro studies showed the effect of these cytokines on DEGs such as  ADAMTS1 ,  -4 ,  -5 ,  -9 , and  HK2  in endometrial fibroblasts at different stages of endometrosis. The effect of cytokines on ADAMTS members’ gene transcription in fibroblasts differs according to the severity of endometrosis. The identified transcriptomic changes associated with endometrosis suggest that inflammation and metabolic changes are features of mild and moderate stages of endometrosis. The changes of  ADAMTS-1 ,  -4 ,  -5 ,  -9 , in fibrotic  endometrium  as well as in endometrial fibroblast in response to TGF-β1, IL-4, IL-13, and IL-17 suggest the important role of these factors in the development of endometrosis.