In vitro models for testicular steroidogenesis: current status and future perspectives

Area of Science:

• Endocrinology and Toxicology
• Reproductive Biology
• In Vitro Toxicology

Background:

• Testicular steroidogenesis is vital for male reproductive health but poorly understood due to chemical disruptions.
• Current in vitro models, like the H295R assay, lack male gonadal specificity.
• Animal models present ethical and logistical hurdles for chemical safety testing.

Purpose of the Study:

• To review and assess in vitro models for evaluating chemical impacts on testicular steroidogenesis.
• To identify limitations in current models regarding species, development, and pathway replication.
• To propose advancements for more predictive and standardized testicular in vitro testing.

Main Methods:

• Semi-systematic review of over 1500 studies on testicular in vitro models.
• Analysis of primary Leydig cells, cell lines, stem cell-derived models, and 3D testicular systems.
• Targeted full-text analysis of 23 reference chemicals across H295R and eight testicular models.

Main Results:

• Most models use rodent, cancerous cell lines in 2D, with limited human/immature cell representation.
• Forskolin, genistein, prochloraz, and ketoconazole showed consistent effects as reference compounds.
• Data on chemical effects in testicular models are scarce and inconsistent, especially for androstenedione and progesterone.

Conclusions:

• Current in vitro models need significant improvement and standardization for reliable chemical safety assessment.
• Development of hormone-responsive, species- and stage-specific models is essential.
• Enhanced models will improve chemical safety evaluation and support regulatory acceptance of alternative methods.