Author:
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.
Abstract
AbstractIn 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.
Publisher
Springer Science and Business Media LLC
Reference58 articles.
1. Kenney, R. M. Cyclic and pathologic changes of the mare endometrium as detected by biopsy, with a note on early embryonic death. J. Am. Vet. Med. Assoc. 172, 241–262 (1978).
2. Kenney, R. M. & Doig, P. A. Equine endometrial biopsy. In Current Therapy in Theriogenology Vol. 2 (ed. Morrow, D. A.) 726–29 (Saunders WB, 1986).
3. Hoffmann, C. et al. The equine endometrosis: New insights into the pathogenesis. Anim. Reprod. Sci. 111, 261–78 (2009).
4. Lehmann, J. et al. Morpho-functional studies regarding the fertility prognosis of mares suffering from equine endometrosis. Theriogenology 76, 1326–1336 (2011).
5. Zeisberg, M. & Kalluri, R. Cellular mechanisms of tissue fibrosis. 1. Common and organ-specific mechanisms associated with tissue fibrosis. Am. J. Physiol. Cell Physiol. 304, C216-25 (2013).