More than just hormones: H295R cells as predictors of reproductive toxicity

Area of Science:

• Toxicology
• Endocrinology
• Cell Biology

Background:

• Therapeutic compounds can cause reproductive toxicities by disrupting the steroidogenic pathway.
• Developing predictive assays for reproductive toxicity is crucial for drug safety.

Purpose of the Study:

• To develop a high-throughput in vitro assay for predicting chemical-induced reproductive toxicity.
• To validate the H295R cell line as a model for assessing steroidogenic pathway disruption.

Main Methods:

• H295R cells were treated with 83 known-positive and 79 known-negative compounds.
• Assayed expression of key steroidogenic enzymes (STAR, 3βHSD2, CYP17A1, CYP11B2, CYP19A1, CYP21A2, CYP11A1).
• Measured levels of steroid hormones (DHEA, progesterone, testosterone, cortisol).

Main Results:

• A Random Forest model was employed for prediction.
• Achieved a receiver operating characteristic area under the curve (ROC AUC) of 0.845.
• Demonstrated a sensitivity of 0.724 and specificity of 0.758 for predicting in vivo reproductive toxicity.

Conclusions:

• The developed in vitro assay effectively predicts in vivo reproductive toxicity.
• H295R cells provide a viable model for high-throughput screening of reproductive toxicants.
• This assay can aid in early identification of potential reproductive risks associated with chemical compounds.