Two Hits of EDCs Three Generations Apart: Effects on Social Behaviors in Rats, and Analysis by Machine Learning

Area of Science:

• Environmental toxicology
• Behavioral neuroscience
• Reproductive biology

Background:

• Endocrine-disrupting chemicals (EDCs) pose risks through direct and ancestral exposure.
• The interaction between direct and ancestral EDC exposure on behavior is unknown.
• Social behaviors are crucial for species survival and reproduction and are sensitive to environmental factors.

Purpose of the Study:

• To investigate the interactive effects of direct and ancestral exposure to EDCs on social behaviors.
• To examine transgenerational effects of EDCs across six generations in a rat model.
• To determine sex and lineage-specific differences in behavioral responses to EDC exposure.

Main Methods:

• A novel "two hits, three generations apart" rat model was employed.
• Two classes of EDCs (PCBs and Vinclozolin) were administered to pregnant dams (F0).
• Social behaviors (sociability, social novelty) were assessed in multiple generations (F1, F3, F4, F6) using machine learning (DeepLabCut).

Main Results:

• Social behaviors were significantly affected by ancestral EDC exposure, but not by direct exposure.
• Females from paternally exposed lineages showed particular vulnerability.
• Effects varied by EDC type and generation, with Vinclozolin impacting the F3 and PCBs impacting F3 and F6 generations.

Conclusions:

• Behavioral deficits are primarily linked to heritable ancestral exposure to EDC contamination.
• Sex and breeding lineage are critical factors influencing transgenerational EDC outcomes.
• This study highlights the long-term, heritable impact of environmental contaminants on social behavior.