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

Framework: Horizon Europe — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator grants
Action type: ERC actions
Panel: Prevention,  Diagnosis and T reatment of Human Diseases
Panel description: Medical technologies  and tools for prevention, diagnosis and treatment of human diseases, therapeutic approaches and interventions , pharmacology, preventative  medicine, epidemiology and public health , digital medicine
Countries involved: Sweden
Call: ERC CONSOLIDATOR GRANTS (ERC-2023-COG, 2023)
Start date: 2024-10-01
End date: 2029-09-30
Duration (months): 60.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: SIGNED

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.

Keywords: reproductive toxicology,human made chemicals,endocrine disrupting chemicals,non toxic environment,infertility,female fertility,human ovaries,human embryos,human stem cells,human ovarian tissue culture,ovarian follicles,ovarian reserve,oocyte,organoid,blastoid model,implantation,single cell multi omics,mechanisms,reporter genes,in vitro assays,cell culture,high content assay,chemical health risk assessment