Gene expression profile of endometrium in receptive state in women with adenomyosis

Abstract

Nižja stopnja zanositve pri ženskah z adenomiozo maternice se povezuje z ovirano endometrijsko receptivnostjo za vgnezdenje zarodka. Pripadajoči molekularni vzroki so slabo raziskani zaradi preteklih tehnoloških omejitev neinvazivnih diagnostičnih metod za odkrivanje adenomioze. S pristopi sistemske biologije smo zato identificirali kandidatne biološke poti/gene spremenjene endometrijske receptivnosti pri adenomiozi. Izvedli smo analizo RNA sekvenciranja (RNA-seq) endometrija v pričakovanem stanju receptivnosti ženskam z (n = 10) in brez (n = 10) ultrazvočnih znakov adenomioze. Identificirane spremenjeno izražene gene smo dalje integrirali s podatki iz pregleda literature, da bi razumeli njihov pomen v povezavi z molekularno biologijo endometrija. Zbrali smo poročane transkripte in proteine, povezane z endometrijsko receptivnostjo pri adenomiozi, pri sorodni, a bolje raziskani endometriozi in pri zdravi maternici, ter poenotili njihovo poimenovanje po genski nomeklaturi zbirke HGNC. S primerjavo podatkov RNA-seq samo potrjeno receptivnih vzorcev (8 adenomioznih in 5 kontrolnih) smo zaznali 382 spremenjeno izraženih genov (p 0,05), kar bi lahko bila posledica nizkega števila uporabljenih vzorcev. Na podlagi analize podatkov iz dosedanje literature in lastnih rezultatov RNA-seq sklepamo, da je endometrijska receptivnost pri ženskah z adenomiozo spremenjena na ravni signalizacije s citokini imunskega sistema.Lower pregnancy rate in women with uterine adenomyosis is associated with impaired endometrial receptivity for embryo implantation. The underlying molecular causes are poorly understood due to past technological limitations of non-invasive methods to diagnose adenomyosis. We therefore applied systems biology approaches to identify candidate biological pathways/genes of altered endometrial receptivity in adenomyosis. We performed RNA sequencing (RNA-seq) analysis of the endometrium in the expected receptive state in women with (n = 10) and without (n = 10) ultrasound signs of adenomyosis. The identified differentially expressed genes were further integrated with data from the literature mining to understand their relevance in the context of endometrial molecular biology. We gathered reported transcripts and proteins associated with endometrial receptivity in adenomyosis, in related but better-studied endometriosis and in healthy uterus, and adopted their gene nomenclature according to the HGNC database. The comparison of RNA-seq data of only confirmed receptive samples (8 adenomyosis and 5 controls) identified 382 differentially expressed genes (p 0.05), which may be due to the small sample size. Based on the analysis of existing literature and own RNA-seq results, we conclude that endometrial receptivity in adenomyosis is altered at the level of immune cytokine signalling

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