Abstract
All individuals are directly exposed to extant environmental endocrine-disrupting chemicals (EDCs), and indirectly exposed through transgenerational inheritance from our ancestors. Although direct and ancestral exposures can each lead to deficits in behaviors, their interactions are not known. Here we focused on social behaviors based on evidence of their vulnerability to direct or ancestral exposures, together with their importance in reproduction and survival of a species. Using a novel “two hits, three generations apart” experimental rat model, we investigated interactions of two classes of EDCs across six generations. PCBs (a weakly estrogenic mixture Aroclor 1221, 1 mg/kg), Vinclozolin (antiandrogenic, 1 mg/kg) or vehicle (6% DMSO in sesame oil) were administered to pregnant rat dams (F0) to directly expose the F1 generation, with subsequent breeding through paternal or maternal lines. A second EDC hit was given to F3 dams, thereby exposing the F4 generation, with breeding through the F6 generation. Approximately 1200 male and female rats from F1, F3, F4 and F6 generations were run through tests of sociability and social novelty as indices of social preference. We leveraged machine learning using DeepLabCut to analyze nuanced social behaviors such as nose touching with accuracy similar to a human scorer. Surprisingly, social behaviors were affected in ancestrally exposed but not directly exposed individuals, particularly females from a paternally exposed breeding lineage. Effects varied by EDC: Vinclozolin affected aspects of behavior in the F3 generation while PCBs affected both the F3 and F6 generations. Taken together, our data suggest that specific aspects of behavior are particularly vulnerable to heritable ancestral exposure of EDC contamination, that there are sex differences, and that lineage is a key factor in transgenerational outcomes.
Highlights
We live in a world that is irreversibly contaminated as a consequence of the chemical revolution that began in the 1940s
Evident in the results, decipher the combinatorial effects of multigenerational exposures to legacy and contemwere concepts that are critical to research on endocrine-disrupting chemicals (EDCs)
Evident in the results, were to direct exposures to environmental toxicants, especially during critical developmental concepts arehormone critical to research on EDCs
Summary
We live in a world that is irreversibly contaminated as a consequence of the chemical revolution that began in the 1940s. The industrial, agricultural, and pharmaceutical industries, to name only a few, have produced hundreds of thousands of chemicals, among which nearly 1000 are classified as endocrine-disrupting chemicals (EDCs) [1,2]. The consequences of EDC exposure are manifested as endocrine and neurological disorders in individuals directly exposed, especially during sensitive life stages such as fetal development. Exposure can cause disease and dysfunction for multiple generations without additional exposure due to heritable epigenetic mechanisms [3,4]. The complex diseases and dysfunctions associated with EDCs represent the interaction of historical and contemporary exposures. The complexities arising from nearly a century of EDC exposure—about five generations in humans and hundreds of generations in rodents — must be studied in a laboratory setting if there is any hope that we can anticipate similar issues arising in humans
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
