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Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals,

Pierre Gaudriault1,2, Séverine Mazaud-Guittot1,2, Vincent Lavoué3

  • 1IRSET INSERM UMR1085 , Rennes, France.

Environmental Health Perspectives
|August 11, 2017
PubMed
Abstract

Insights

Mixtures of anti-androgenic chemicals can suppress testosterone synthesis in human fetal testes more than individual compounds. This finding is crucial for assessing risks from combined chemical exposures during fetal development.

Area of Science:

  • Endocrinology
  • Toxicology
  • Developmental Biology

Background:

  • Chemicals can disrupt androgen production, with potential adverse effects on male reproductive development.
  • The combined effects of chemical mixtures on androgen synthesis in human tissues are not well understood.
  • Fetal exposure to androgen-disrupting chemicals is linked to reproductive health issues later in life.

Purpose of the Study:

  • To investigate if chemicals act synergistically to disrupt androgen production in human fetal testes.
  • To evaluate the significance of mixture effects in hazard characterization of anti-androgenic chemicals.
  • To establish a predictive human mixture risk assessment for fetal anti-androgenic exposures.

Main Methods:

  • Utilized an organotypic culture system of human fetal testes explants (FEtal Gonad Assay - FEGA).
  • Screened 27 chemicals individually for anti-androgenic effects in human fetal testes (gestational weeks 10-12).
  • Tested 11 selected compounds in mixtures of four and eight components, including pharmaceuticals and pesticides.

Main Results:

  • Mixtures of anti-androgens suppressed testosterone synthesis in human fetal testicular explants more than individual chemicals.
  • Observed a leftward shift in dose-response curves for individual anti-androgens as mixture complexity increased.
  • The impact of mixture effects was more pronounced with eight components compared to four.

Conclusions:

  • Human fetal testes explants can be used to predict mixture effects of anti-androgenic chemicals.
  • Mixture effects significantly alter the hazard assessment of individual anti-androgenic compounds.
  • Established foundations for a predictive human mixture risk assessment approach for fetal anti-androgenic exposures.

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