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Oogenesis spotlighted: making mature human oocytes

Objective

Women who survive childhood cancer often fail to conceive because their eggs are damaged by (gonadotoxic) chemotherapy. A major breakthrough has been the possibility to cryopreserve cortical strips of their ovarian tissue for autologous transplantation later in life. This has led to over 40 successful pregnancies worldwide, the latest in the Netherlands. However, the risk of reintroducing cancer cells with the ovarian graft in patients with previous hematopoietic malignancies is too great and alternatives are needed.
Here, I propose to build on my expertise in gametogenesis in mice and humans and perform a detailed study of the cellular networks and molecular pathways that control development and maturation of the oocyte within the human ovary. We have access and ethical approval for research on human foetal tissue and postnatal ovarian biopsies over a wide age range. I will use this rare material to systematically benchmark the transcriptional profile of cells in the human ovary (oocytes as well as somatic cells) during development and adulthood using Drop-seq, a novel cost-efficient single-cell technology that allows the profiling of thousands of cells in a matter of hours. Thereafter, we will apply mathematical algorithms to reveal cellular identities, developmental trajectories and signalling networks that control oogenesis. With this knowledge, I plan to engineer a human follicular niche creating a “mini-ovary” in vitro that could support the formation and maturation of the oocyte (using patient-specific cells) and to explore mechanisms of follicle maturation through a xenotransplantation mouse model. The cellular outcomes of these assays will be sequenced using Drop-seq and directly compared to their in vivo counterparts.
Our approach will lead to more effective personalized-therapy for fertility preservation and contribute to the development of an in vitro mini-ovary organoid model to use in human reproductive toxicology and disease modelling.

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-COG

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Host institution

ACADEMISCH ZIEKENHUIS LEIDEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 000 000,00
Address
ALBINUSDREEF 2
2333 ZA Leiden
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 000 000,00

Beneficiaries (1)

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