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Developing a human-based stem cell model for reproductive toxicity

Objective

Environmental factors and chemicals are thought to be one cause of declining male fertility. Reproductive toxicity is becoming a major public health problem. Currently, new pharmacological or chemical compounds are tested in animals for their effects on reproduction before entering the market. This risk assessment is essential but time-consuming, expensive and is not always predictive in humans since animals have different reproductive characteristics and physiology. A validated and qualified human system to assess reproductive toxicity would be invaluable in addressing this conundrum between regulatory requirements and true relevance.

Through my ERC-CoG, I have built a large repository of knowledge and developed robust technology on human in vitro gametogenesis, more specifically on how to generate male gamete progenitors from human pluripotent stem cells. This, together with my bioinformatics knowhow, makes me exceptionally well-placed to optimise a human-based high-throughput screening assay for male reproductive toxicity for use by the private sector in filing reproductive safety data to the regulatory authorities. This ReproTox assay will be further optimised (increase throughput, standardise measurements) and integrated with a software innovation (machine learning algorithm to automate quantification and webtool), before we carry out a pilot screen using FDA-approved spermatotoxic compounds and market research to define the commercialisation route.

Reducing the number of compounds that show male reproductive toxicity at very early stages of drug development will contribute to an effective first-tier toxicity screening, not only providing standard protocols for quantitative, rapid, cost-effective, high-throughput, scalable and reproducible toxicity testing, but also reducing, perhaps eventually replacing animal use. ReproTox will ultimately lead to economic, societal, environmental, health and ethical benefits.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

(opens in new window) ERC-2024-POC

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Host institution

ACADEMISCH ZIEKENHUIS LEIDEN
Net EU contribution
€ 150 000,00
Address
ALBINUSDREEF 2
2333 ZA Leiden
Netherlands
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Beneficiaries (1)