Understanding the mechanisms of endometrial receptivity through integration of ‘omics’ data layers
Date
2020-05-28
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Abstract
Maailma Terviseorganisatsiooni statistika väidab, et umbes 10% püsisuhetes olevatest naistest on ühel või teisel põhjusel viljatud. Naise viljakust mõjutab välja palju erinevaid faktoreid ning setõttu on viljatuse põhjuste leidmine tihti väga keeruline. Viljatust põhjustavateks faktoriteks võivad olla üldine terviseseisund, erinevad haigused, geneetiline taust, väliskeskkonna ja eluviisiga seotud tegurid. Ühe näitena võib tuua embrüo pesastumist (implantatsioon) emaka limaskesta (endomeetriumi), mis võib toimuda ainult kindla lühikese perioodi vältel (implantatsiooni aken), kui endomeetrium on embrüo suhtes kõige vastuvõtlikum. Implantatsiooni akna periood on aga iga naise jaoks erinev, ning on määratud erinevate bioloogiliste protsesside poolt. Kunstliku viljastamise (IVF) läbiviimise jaoks on kriitiline teada täpset implantatsiooni akna aega, sellega seotud mehhanisme ja nende vastastikust mõju. Selleks, et uurida mehhanismide omavahelisi seoseid, panime paariviisiliselt kokku erinevaid geneetilise regulatsiooni andmekihte, milleks olid RNA, mikroRNA ja DNA metülatsiooni admed, ja mida koos nimetatakse ‘oomika’ andmekihtideks. Kokkuvõtvalt näitavad antud töö tulemused, et, võrreldes ühe ‘oomika’ andmekihi uurimisega, ‘oomika’ andmekihtide kombineerimine aitab paremini mõista endomeetriumi retseptiivsusega seotud bioloogilisi protsesse ning vältida valepositiivseid tulemusi. Antud tööga me rõhutame süsteemibioloogia ning paljude andmekihtide samaaegse kasutamise olulisust naise reproduktiivsuse bioloogiliste mehhanismide uurimisel.
According to the World Health Organization, over 10% of females in a stable relationship are suffering from involuntary infertility/subfertility worldwide. Untangling the reasons for this is difficult because female reproduction is a sophisticated matter and can be affected by many factors such as health, accompanying diseases, genetic background, environment, and lifestyle. As a specific example, embryo implantation – its attachment to the uterine lining (endometrium) – occurs only during a relatively short period of time, called the window of implantation (WOI), when the endometrium is most receptive to an embryo. This is critical for a commonly used fertility treatment of in vitro fertilizaton (IVF) – and to make matters more complex, the WOI is not the same for everyone, but adjusted by an interlocking system of biological regulation mechanisms. Thus, to provide successful IVF, it is important to know these exact regulation mechanisms – and, since they interact with one another, to understand how they work together, not just individually. We used pairwise integration of data from different layers of genetic regulation, such as RNA, microRNA, and DNA methylation, called together the ‘omics’ layers, and showed the advantage of the data integration approach over the usage of just a single ‘omics’ layer. As a result, we obtained the lists of novel potential biomarkers that could regulate WOI, validated some previously known receptivity biomarkers, and showed that integration of different ‘omics’ layers helps to avoid false-positive results. With our work, we encourage other researchers in the female reproduction field to integrate several data layers for further studies
According to the World Health Organization, over 10% of females in a stable relationship are suffering from involuntary infertility/subfertility worldwide. Untangling the reasons for this is difficult because female reproduction is a sophisticated matter and can be affected by many factors such as health, accompanying diseases, genetic background, environment, and lifestyle. As a specific example, embryo implantation – its attachment to the uterine lining (endometrium) – occurs only during a relatively short period of time, called the window of implantation (WOI), when the endometrium is most receptive to an embryo. This is critical for a commonly used fertility treatment of in vitro fertilizaton (IVF) – and to make matters more complex, the WOI is not the same for everyone, but adjusted by an interlocking system of biological regulation mechanisms. Thus, to provide successful IVF, it is important to know these exact regulation mechanisms – and, since they interact with one another, to understand how they work together, not just individually. We used pairwise integration of data from different layers of genetic regulation, such as RNA, microRNA, and DNA methylation, called together the ‘omics’ layers, and showed the advantage of the data integration approach over the usage of just a single ‘omics’ layer. As a result, we obtained the lists of novel potential biomarkers that could regulate WOI, validated some previously known receptivity biomarkers, and showed that integration of different ‘omics’ layers helps to avoid false-positive results. With our work, we encourage other researchers in the female reproduction field to integrate several data layers for further studies
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Keywords
endometrium, implantation, gene expression, DNA methylation, microRNA, correlation analysis, bioinformatics, epigenetics