Single-cell toxicology for detailed analysis of adverse outcome pathways in human ovary

Decreasing sperm counts have attracted substantial attention and stimulated discussions about reproductive toxicity of chemicals in men. Similar endpoints have never been measured in women.

While semen is easily available and analyzed, oocytes quietly reside in ovarian follicles without giving clear signals of quality or quantity. Nevertheless, recent reviews suggest that female reproductive health may be threatened by chemicals.

Our studies on human ovarian tissue have shown that viability, growth and function of follicles can be affected by chemical exposures.

However, identification of the underlying mechanisms, which is crucial for development of predictive assays and regulation of chemicals, has proven challenging due to the sheer complexity of ovarian tissue and follicle growth.

Ovaries are highly heterogeneous tissue composed of multiple cell populations whose interactions play a crucial role in follicle growth. In addition, cell proportions naturally vary between women.

Therefore, subtle changes in differentiation processes and cell-type specific responses can easily be lost in bulk tissue analysis. We have set up a single-cell analysis pipeline for ovarian tissue and mapped all cell types in he human ovary. Here, we will apply this method to analyze ovarian tissue exposed to chemicals on a single-cell level.

The results will reveal mechanisms of toxicity in target cell types and aid in building adverse outcome pathways for better chemical health risk assessment.