The putative role of microRNAs in endometriosis pathogenesis and potential in diagnostics
Date
2019-07-04
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Abstract
Endometrioos on sage günekoloogiline haigus, mille korral emaka limaskest ehk endomeetrium kasvab kolletena väljaspool emakaõõnt. Haigusega kaasnevad sageli tugevad kõhuvalud ja viljatus. Vaatamata ulatuslikele uuringutele on endiselt ebaselge, miks mõnel naisel endomeetriumi rakud vales asukohas püsima jäävad ja kasvama hakkavad. Probleemiks on ka endometrioosi diagnoosimise piiratud võimalused, mistõttu ainus viis haiguse lõplikuks kindlakstegemiseks on invasiivne operatsioon. Viimasel ajal on uute endometrioosi patogeneesi kandidaatmarkeritena pakutud välja mikroRNA-sid (miRNA-d). miRNA-d on lühikesed RNA molekulid, mis reguleerivad geeniekspressiooni nii normaalsete kui ka patoloogiliste seisundite, muu hulgas endometrioosi korral. miRNA-sid on võimalik tuvastada ka kehavedelikest, mis teeb neist potentsiaalsed biomarkeri kandidaadid haiguse diagnoosimiseks. Minu uuringute eesmärgiks oligi välja selgitada miRNA-de võimalikke rolle endometrioosi patogeneesis ja hinnata spetsiifiliste vereplasma miRNA-de sobivust endometrioosi biomarkeritena. Näitasime, et vereplasma miRNA-de tase ei ole naistel mõjutatud menstruaaltsüklist ja kindlad vereplasma miRNA-d võimaldavad eristada endometrioosiga naisi patsientidest, kellel haigust ei esine. Samas avastasime, et haigusest mittesõltuvad tegurid, nagu ööpäevarütm ja individuaalne varieeruvus mõjutavad miRNA tasemeid sellisel määral, et nende võimekus endometrioosi kliiniliste biomarkeritena on vähene. Lisaks võimaldas uuringu uudne lähenemine, kus kasutasime miRNA tasemete tuvastamiseks endometrioosi kolletes kindlat rakupopulatsiooni terve koe asemel, välja pakkuda võimalikke mehhanisme, mis viivad endometrioosiga kaasneva valu ja viljatuse tekkeni.
Endometriosis is a painful condition in which the endometrium grows outside the uterus usually on the surfaces of pelvic organs. The disease is often accompanied by severe abdominal pain and infertility. Despite the extensive research, the exact reason why the endometrial cells implant and survive in the wrong location is still unclear. Also, the diagnostic options for endometriosis are limited and the only way for definite diagnosis is an invasive surgery. Most recently, microRNAs (miRNAs) have emerged as novel candidate markers for the disease pathogenesis. miRNAs are small RNA molecules that have a regulatory effect on gene expression in both normal physiological and pathological conditions including endometriosis. miRNAs can also be detected in body fluids, making them potential biomarker candidates for the disease diagnostics. The aim of the study was to assess the role of miRNAs in the pathogenesis of endometriosis and to evaluate the suitability of specific miRNAs in blood plasma as endometriosis biomarkers. We showed that plasma miRNA levels are not influenced by the menstrual cycle and certain miRNA levels in blood allow to distinguish women with endometriosis from patients without the disease. However, we discovered several other factors, such as circadian rhythm and individual variability, that influence plasma miRNA levels to an extent that their ability as clinical biomarkers of endometriosis is limited. In addition, a novel approach to analysing miRNAs in endometriotic lesions was applied in this study, where a specific cell population instead of a whole tissue was used. This analysis revealed possible mechanisms that lead to endometriosis-associated pain and infertility.
Endometriosis is a painful condition in which the endometrium grows outside the uterus usually on the surfaces of pelvic organs. The disease is often accompanied by severe abdominal pain and infertility. Despite the extensive research, the exact reason why the endometrial cells implant and survive in the wrong location is still unclear. Also, the diagnostic options for endometriosis are limited and the only way for definite diagnosis is an invasive surgery. Most recently, microRNAs (miRNAs) have emerged as novel candidate markers for the disease pathogenesis. miRNAs are small RNA molecules that have a regulatory effect on gene expression in both normal physiological and pathological conditions including endometriosis. miRNAs can also be detected in body fluids, making them potential biomarker candidates for the disease diagnostics. The aim of the study was to assess the role of miRNAs in the pathogenesis of endometriosis and to evaluate the suitability of specific miRNAs in blood plasma as endometriosis biomarkers. We showed that plasma miRNA levels are not influenced by the menstrual cycle and certain miRNA levels in blood allow to distinguish women with endometriosis from patients without the disease. However, we discovered several other factors, such as circadian rhythm and individual variability, that influence plasma miRNA levels to an extent that their ability as clinical biomarkers of endometriosis is limited. In addition, a novel approach to analysing miRNAs in endometriotic lesions was applied in this study, where a specific cell population instead of a whole tissue was used. This analysis revealed possible mechanisms that lead to endometriosis-associated pain and infertility.
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Keywords
endometrioos, patogenees, biomarkerid, mikroRNA, diagnostika (med.), ööpäevarütm