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Dynamics of embryo-endometrial communication mediated by extracellular vesicles

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dc.contributor.advisorFazeli, Alireza (advisor)
dc.contributor.authorMuhamdiram, Subhashini
dc.contributor.departmentInstitute of Veterinary Medicine and Animal Scienceseng
dc.contributor.otherBabalouka, Dimitrios Rizos (opponent)
dc.date.accessioned2025-04-10T11:18:26Z
dc.date.available2025-04-10T11:18:26Z
dc.date.defensed2025-05-19
dc.date.issued2025
dc.descriptionA Thesis for applying for the degree of Doctor of Philosophy in Veterinary Science.eng
dc.descriptionVäitekiri filosoofiadoktori kraadi taotlemiseks loomaarstiteaduse erialal.est
dc.description.abstractABSTRACT. There has been a global decline in fertility rates in both humans and animals. Embryo implantation, the process by which the embryo attaches to the endometrium, is the first key step in establishing a pregnancy. Effective communication between the embryo and endometrium prior to implantation is essential for achieving a successful pregnancy. Although various cytokines, growth factors, and hormones are believed to play a role in this dialogue, recent research has highlighted the role of extracellular vesicles (EVs) in this interplay. However, the exact mechanisms of EV function in this context are still not completely understood. The main aim of this doctoral study was to identify a protein indicator of embryo-maternal dialogue mediated via EVs and use it to better understand the factors that influence this critical interplay preceding implantation. Using an in vitro embryo implantation model, we demonstrated that embryonic signals, delivered via EVs, can prime receptive endometrial epithelial cells to enrich their secretory proteome with key proteins vital for embryo implantation. Notably, we identified increased secretion of the MFGE8 protein from endometrial cells in response to embryonic EVs, serving as a marker of embryo-maternal communication. Our findings showed that EV mediated embryo maternal dialogue was influenced by a range of factors, including hormonal levels, the receptivity status of endometrial cells, the trophoblast cell microenvironment, EV dose, and the duration of EV-cell interaction. These results suggest that EV-mediated embryo-maternal communication may rely on both embryonic and endometrial factors. The findings of this PhD thesis could pave the way for a deeper understanding of the mechanisms through which embryonic EVs influence implantation, offering new opportunities to enhance fertility treatments for humans and animals.eng
dc.description.abstractLĂœHIKOKKUVĂ•TE. Kogu maailmas väheneb nii inimeste kui ka produktiivloomade viljakus. EmbrĂ¼o ja endomeetriumi rakusuhtlus enne implantatsiooni on siinkohal kriitiliselt oluline. Molekulaarse signaaliraja mehhanismid embrĂ¼o kinnitumisel endomeetriumile e implanteerumisel ei ole veel selgelt teada. Hiljutised uuringud näitavad, et tsĂ¼tokiinide, kasvufaktorite ja hormoonide kõrval on oluline roll rakuvälistel vesiikulitel (extracellular vesicles, EV). Doktoritöö Ă¼ldeesmärk oli tuvastada valgumarker, mis iseloomustab EV-de vahendatavat embrĂ¼o ja endomeetriumi rakusuhtluse dĂ¼naamikat. Alameesmärgina uuriti selle valgumarkeri funktsionaalsust, et paremini mõista tegureid, mis mõjutavad implanteerumisele eelnevaid protsesse. Tulemused näitasid, et EV-de vahendatud signaalid võivad ette valmistada endomeetriumi epiteelirakke, mille proteoom rikastub embrĂ¼o implanteerumise jaoks oluliste sekretoorsete valkudega. Töös tuvastati ka embrĂ¼o ja endomeetriumi rakusuhtluse markerina toimiva valgu MFGE8 suurenenud eritumine endomeetriumi rakkudest vastusena embrĂ¼o EV-dele. Sekreteerumise suurenemist mõjutasid mitu tegurit, sh hormonaalne tase, endomeetriumi rakkude vastuvõtlikkus, trofoblastirakkude mikrokeskkond, EV-de annus ja EV-de mõju kestus. Tulemused viitavad sellele, et EV-de vahendatavat embrĂ¼o ja endomeetriumi rakusuhtlust võivad mõjutada nii embrĂ¼onaalsed kui ka endomeetriumist tulenevad tegurid. Valgu MFGE8 sekretsiooni tase ja in vitro embrĂ¼o implanteerumise mudel toetavad EV-de vahendatud mehhanismide selgitamist embrĂ¼o ja endomeetriumi rakusuhtluses.est
dc.description.sponsorshipThe publication of this dissertation is granted by the Estonian University of Life Sciences and supported by European Union’s Horizon 2020 research and innovation programme under grant agreement No 857418 COMBIVET and the European Union through Horizon coordination and support actions under grant agreement No. 101079349 OH-Boost.
dc.identifier.isbn978-9916-91-018-4 (trĂ¼kis)
dc.identifier.isbn978-9916-91-019-1 (pdf)
dc.identifier.issn2382-7076
dc.identifier.urihttp://hdl.handle.net/10492/9574
dc.publisherEstonian University of Life Scienceseng
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/857418/EU/COMBIVETeng
dc.relation.ispartofseriesDoctoral Theses of the Estonian University of Life Scienceseng
dc.relation.ispartofseriesEesti MaaĂ¼likooli doktoritöödest
dc.rights© Subhashini Muhamdiram, 2025
dc.rightsinfo:eu-repo/semantics/openAccesseng
dc.rights.urihttps://www.riigiteataja.ee/en/eli/ee/Riigikogu/act/519062017005/consolideest
dc.subjectextracellular vesicleseng
dc.subjectembryoeng
dc.subjectendometriumeng
dc.subjectintercellular communicationeng
dc.subjectproteomicseng
dc.subjectdissertationseng
dc.titleDynamics of embryo-endometrial communication mediated by extracellular vesicleseng
dc.title.alternativeRakuväliste vesiikulite vahendatav embrĂ¼o ja endomeetriumi rakusuhtluse dĂ¼naamikaest
dc.typeDoctoral Thesiseng
dc.type.qualificationnamePhD

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