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

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Existing in vitro models inadequately assess testicular steroidogenesis disruption by chemicals. Improved, standardized testicular models are crucial for accurate chemical safety assessment and male reproductive health research.

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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.