Characterization of the maternal reproductive tract and spermatozoa communication during periconception period via extracellular vesicles
Date
2023-07-17
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Abstract
Naiste viljatus võib olla tingitud mitmetest teguritest, mida laialdaselt jagatakse eostamiseelseteks ja -järgseteks probleemideks. Munajuha mängib võtmerolli eostamiseelse keskkonna loomisel, millel on osa sugurakkude edukal transpordil, meessugurakkude küpsemisel, viljastumisel ja varajases embrüoarengus. Olgugi, et mitmed olulised sündmused edukaks raseduseks leiavad aset munajuhas, on teave munajuha eostamiseelsest miljööst puudulik. Hoolimata, et tehtud on märkimisväärseid edusamme kunstliku viljastamise tehnoloogias (ART) alates sellest, kui teostati esimene edukas rasedus in vitro viljastamisega (IVF) 1978 aastal, ei ole ART-i abil rasestumine alati garanteeritud ja paljud paarid peavad lapse saamiseks läbima mitu kuntsliku viljastamise ravikuuri. Lisaks ligikaudu 30% paaridest, kellel on diagnoositud viljatus.
Mitmed uuringud on kirjeldanud spermatosoidide mõjust munajuha genoomse ja proteoomilsele profiilile. Nende muutuste tekkimiseks on vaja sobilikku täpset rakkudevahelist suhtlust, mille üheks viisiks on rakkudel kasutada sõnumitoojatena ekstratsellulaarseid ehk rakkudevahelisi vesiikuleid (EV). Munajuha epiteelrakkude EV-d mängivad olulist rolli spermatosoidide liikuvuse, elujõulisuse ja transpordi toetamisel. Omakorda munajuha transkriptoomi mõjutavad follikulaarse vedeliku (FF) EV-d, mis satuvad munajuhasse munaraku vabanemisel folliikulist. Sellest järeldub, et eksisteerib kahepoolne dialoog spermatosoidide ja munajuha ning EV-de vahel, mis võib mängida olulist rolli rakkudevahelises suhtluses.
Selles projektis uuriti spermatosoidide ja munajuha epiteelrakkude võimet suhelda ja muuta munajuha geeniekspressiooni ilma otsekontaktita. Edasi uuriti milliseid munajuha EV-de sisu muutusi põhjustasid spermatosoidid. Lisaks analüüsiti FF EV-de erinevate kontsentratsioonide mõju spermatosoidide elutähtsatele funktsioonidele nagu elujõulisus, kapatsitatsiooni ja akrosomaalne reaktsioon. Kõrvalekalded normaalsest spermatosoidide, munajuha ja FF ning nende EV-de suhtluses võib olla üks viljatuse põhjus. Sellise suhtluse edasised uuringud on vajalikud, pakkudes potentsiaalselt võimalust leida aspekte tõstmaks ART-põhist viljatusravi tõhusust, eriti tuvastamata põhjusega viljatuse korral.
Infertility in women could arise from multiple factors which are broadly seen as issues in the pre-conception or post-conception processes. The oviduct plays key role in maintaining periconception environment and facilitates the transport and maturation of male gametes, fertilization, early embryonic development. Although these notable events take place in oviduct, the information regarding periconception milieu in oviduct is very limited. Despite significant advances in assisted reproductive technologies (ARTs) since the birth of first in vitro fertilization (IVF) baby in 1978, achieving pregnancy through ART is not guaranteed, and many couples require multiple attempts. Approximately 30% of couples diagnosed with infertility globally have idiopathic infertility. Studies have reported modifications in genomic and proteomic profile of the oviduct induced by the presence of spermatozoa. These alterations occurring require precise intercellular communication and a class of messengers called extracellular vesicles (EVs) seem to mediate these interactions. The EVs from oviductal epithelium play important role in supporting spermatozoa motility, and viability. Moreover, follicular fluid (FF), which is a rich source of EVs, has been reported to influence the oviductal transcriptome. Therefore, taken together, these studies imply existence of a two-way dialogue between spermatozoa-oviduct and EVs might be playing a vital role in this interaction. In this project, we investigated if spermatozoa can communicate with oviductal epithelial cells remotely and alter the gene expression of the oviduct without direct interaction. In addition, we also aimed to study the changes in cargo and production of EVs derived from the oviduct in response to spermatozoa. Furthermore, we also analysed the effects of FF derived EVs on vital functions of spermatozoa which includes viability, capacitation and acrosome reaction. The lack of understanding regarding these interactions between spermatozoa-oviduct, spermatozoa-FF and role of EVs as possible mediators of intercellular communication can be one of the reasons leading to failure in conception. An exploration of such processes may enhance ART-based infertility treatments, particularly in case of couples diagnosed with idiopathic infertility
Infertility in women could arise from multiple factors which are broadly seen as issues in the pre-conception or post-conception processes. The oviduct plays key role in maintaining periconception environment and facilitates the transport and maturation of male gametes, fertilization, early embryonic development. Although these notable events take place in oviduct, the information regarding periconception milieu in oviduct is very limited. Despite significant advances in assisted reproductive technologies (ARTs) since the birth of first in vitro fertilization (IVF) baby in 1978, achieving pregnancy through ART is not guaranteed, and many couples require multiple attempts. Approximately 30% of couples diagnosed with infertility globally have idiopathic infertility. Studies have reported modifications in genomic and proteomic profile of the oviduct induced by the presence of spermatozoa. These alterations occurring require precise intercellular communication and a class of messengers called extracellular vesicles (EVs) seem to mediate these interactions. The EVs from oviductal epithelium play important role in supporting spermatozoa motility, and viability. Moreover, follicular fluid (FF), which is a rich source of EVs, has been reported to influence the oviductal transcriptome. Therefore, taken together, these studies imply existence of a two-way dialogue between spermatozoa-oviduct and EVs might be playing a vital role in this interaction. In this project, we investigated if spermatozoa can communicate with oviductal epithelial cells remotely and alter the gene expression of the oviduct without direct interaction. In addition, we also aimed to study the changes in cargo and production of EVs derived from the oviduct in response to spermatozoa. Furthermore, we also analysed the effects of FF derived EVs on vital functions of spermatozoa which includes viability, capacitation and acrosome reaction. The lack of understanding regarding these interactions between spermatozoa-oviduct, spermatozoa-FF and role of EVs as possible mediators of intercellular communication can be one of the reasons leading to failure in conception. An exploration of such processes may enhance ART-based infertility treatments, particularly in case of couples diagnosed with idiopathic infertility
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Keywords
reproductive health, infecundity, fertilization, intercellular communication, extracellular vesicles, gametes, uterus, fallopian tubes, epithelial cells, spermatozoa