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.
