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

Introduction

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.

European Growth Strategy

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.

Project Overview

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.

Methodology

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:

1. Ubiquitous presence in women
2. 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.

Impact

Taken together, SAFER sets an example for animal-free derivation of assays for chemical safety assessment. SAFER tools will contribute to the 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.

Conclusion

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.