H2020Individual fellowship2020–2022

EXORep · EXOsomes as a new strategy in Assisted Reproductive Technologies: tracing maternal nanomessengers to improve pregnancy outcomes

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-09-01 → 2022-08-31
EU contribution
€191,149
Participants
1
Scheme
MSCA-IF

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Results in brief

EXOsomes as a new strategy in Assisted Reproductive Technologies: tracing maternal nanomessengers to improve pregnancy outcomes

Assisted reproductive technologies (ART) have come a long way in the last 30 years both in animals and humans and are well established in the clinical practice. In vitro embryo production (IVP) is performed and transfer of embryos at the blastocyst stage to achieve successful pregnancy. However, even after improvements of the technology, the quality of IVP embryos is still lower compared to the in vivo ones. The lack of embryo-maternal interactions and the maternal signals in the in vitro embryo culture conditions have been postulated as the main reason for the lower embryo quality. Recently, a new mechanism has been proposed pointing at the potential role of extracellular vesicles (EVs) as important mediators of the early embryo-maternal crosstalk. EVs are present in various biofluids and carry different biomolecules such as proteins, nucleic acids (different types of RNAs and DNA), lipids, and metabolites that provide a snapshot of the parental cells at the time of secretion but also transfer specific signaling and regulatory molecules. For example, the EVs’ molecular cargo has been used as biomarkers for diagnosis and prognosis of cancer and other diseases in recent years. Therefore, in the present project, we hypothesized that the oviductal environment as the first site of interactions between the mother and the early embryo, and particularly the oviductal EVs (oEVs) could be important for optimal embryo development. The main objective of this project was to investigate the potentials of oEVs to improve IVP conditions to achieve better pregnancy rates in dairy cattle, but also in humans. The bovine model was used because of its similarities to human during early embryo development. To reach this overall objective, the following specific objectives were addressed: Objective 1. Analysis of oEVs in response to the embryo and its different stages of development (before and after genome activation). Objective 2. Analysis of oEVs in response to good or poor-quality embryos. Objective 3. Identification of crucial molecules contained in oEVs involved in the support of embryo development. Objective 4. Evaluation of the potential ability of oEVs’ to improve ART outcomes.

Data: CORDIS, © European Union

Project objective

The current embryo in vitro culture conditions used in most laboratories of assisted reproductive technologies (ARTs) allow the embryo to develop to the blastocyst stage and to achieve pregnancy. However, the quality of those embryos is suboptimal compared to the in vivo ones and the obtained pregnancy rates are low. The lack of maternal signals, during the in vitro period has been postulated as a main reason for these suboptimal results. There is increasing evidence of the role of the oviduct exosomes (oEXs) as mediators of the early maternal-cross talk. Recent data revealed the first oviduct-derived EXs protein signature and their important roles in embryo-oviduct interactions. In the present proposal, using bovine model, we aimed to: (i) Evaluate whether the presence of the early embryo in the oviduct could modulate the oEXs proteins, mRNA and miRNA content depending on its stage of development. (ii) Assess whether the embryo quality (good or poor embryo) affect the content of EXs secreted in vitro by the oviduct epithelial cells. (ii) Assess the effect of in vitro culture with oEXs on the embryo development and quality. To accomplish these tasks, an ambitious, realistic, work plan has been designed based on the excellent background of the Fellow, and the training she will receive, the expertise of the supervisor in female reproductive physiology and the infrastructure within the host lab for conducing all the experiments with most appropriate tools. This will ensure that the Fellow completes the scientific objectives of the proposal, communicate and disseminate the results to the scientific and public, while acquiring new set of skills that will have an important impact in her career development. If the beneficial effect of oEXs on embryo development is recapitulated in cattle, it could improve in vitro embryo production largely used in ART in dairy cattle industries. Moreover, the obtained results may be transferred in human species

Original text from CORDIS.

Participants

Links

Data: CORDIS, © European Union