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SAfeguarding female FERtility -development of human-relevant in vitro tools for reproductive toxicity

Project description

In vitro tools to screen for reproductive toxins in women

Fertility has been increasing globally for the last three decades. Environmental toxins, often found in everyday products, are a known contributing factor. Scientists lack the tools to assess how chemicals on the European market impact women’s fertility. The ERC-funded SAFER project aims to leverage an extensive ovary biobank, established stem cell lines and multiomics technologies to develop new assays to close this gap. The project will focus on chemicals ubiquitously present in women and known to decrease ovarian function, mapping the mechanisms mediating toxicity in chemically exposed ovarian tissue and stem cell derived embryo model cultures. This understanding will support development of in vitro tools to screen female reproductive toxicants.

Objective

Chemical health risk assessment has failed to safeguard fertility in women. Women and their oocytes are exposed to pervasive mixtures of human-made chemicals that correlate with reproductive ageing and infertility. Only 0.5% of the chemicals on the European market have been well characterized for health risks, and reproductive toxicity in women is typically not covered due to missing tools. The new European Growth Strategy aims at sustainable growth, zero-pollution and safe chemicals. While the need for increased chemical testing is tangible, there is a movement to phase out animal experiments. This creates a huge challenge to deliver on the vision of a safe and toxic-free environment.

Here, I will develop new high-content assays for reproductive toxicity in women. SAFER is built on my exceptional ovary biobank, established stem cell lines, and multi-omics technologies. Using chemically exposed ovarian tissue and stem cell derived blastoid cultures, SAFER will map mechanisms mediating toxicity by high-resolution epigenetic and transcriptomic analyses. Model chemicals are chosen based on ubiquitous presence in women and significant associations to decreased ovarian function, as shown by my cohort studies. The identified mechanisms will be tailored into reporter genes that I will insert into new immortalized human ovarian cells as well as stem cells, and develop into high-content screening assays. The product of SAFER is novel in vitro tools for screening of female reproductive toxicants.

Taken together, SAFER sets an example for animal-free derivation of assays for chemical safety assessment. SAFER tools will contribute to identification and restriction of chemicals that pose a hazard to women’s health. This is an important step in the global movement towards a non-toxic, safe environment.

Starting a family is a basic human right, and whether to have a child or not should be decided by the prospective parents, not by the chemicals in their environment.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-COG

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Host institution

KAROLINSKA INSTITUTET
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
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
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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