The myometrial transcriptome changes in mares with endometrosis.

Mares with endometrosis exhibit histological changes not only in the endometrium but also in the myometrium that suggest possible functional impairment. The molecular background of these changes is not well understood. We hypothesize that the transcriptomic profile of the mare myometrium varies depending on the degree of endometrosis in mares. Myometria were collected from mares in the mid-luteal phase of the estrous cycle with endometrium categories I, IIA, IIB, and III (∑n = 23), according to Kenney and Doig´s histopathological classification. Myometrial RNA was isolated and subjected to RNA-seq analysis to identify differentially expressed transcriptionally active regions (deTARs) and their contribution to signaling pathways (KEGG database) and biological processes (GO terms). In results, 665, 491 and 499 deTARs were found in the myometrium of mares with endometrium IIA vs I, IIB vs I and III vs I, respectively. 200 common deTARs in the myometrium across all stages of endometrosis (IIA, IIB, and III) vs I were identified. Evaluated deTARs enriched several KEGG pathways including calcium signaling, cAMP signaling, oxytocin signaling, ECM-receptor interaction, and focal adhesion, and were classified into various GO terms including adaptive immune response, tissue homeostasis, muscle contractions, muscle development, and other. In conclusion, transcriptomic alterations in the myometrium of mares with endometrosis may indicate an impaired function of the contractile machinery, mechanisms regulating calcium influx and handling, as well as changes in ECM composition, leading to a decreased contractile activity and structural changes in the myometrium of affected mares.