Sexually Dimorphic Effects of Ancestral Exposure to Vinclozolin on Stress Reactivity in Rats
Open accessAbstract
How an individual responds to the environment depends upon both personal life history as well as inherited genetic and epigenetic factors from ancestors. Using a 2-hit, 3 generations apart model, we tested how F3 descendants of rats given in utero exposure to the environmental endocrine-disrupting chemical (EDC) vinclozolin reacted to stress during adolescence in their own lives, focusing on sexually dimorphic phenotypic outcomes. In adulthood, male and female F3 vinclozolin- or vehicle-lineage rats, stressed or nonstressed, were behaviorally characterized on a battery of tests and then euthanized. Serum was used for hormone assays, and brains were used for quantitative PCR and transcriptome analyses. Results showed that the effects of ancestral exposure to vinclozolin converged with stress experienced during adolescence in a sexually dimorphic manner. Debilitating effects were seen at all levels of the phenotype, including physiology, behavior, brain metabolism, gene expression, and genome-wide transcriptome modifications in specific brain nuclei. Additionally, females were significantly more vulnerable than males to transgenerational effects of vinclozolin on anxiety but not sociality tests. This fundamental transformation occurs in a manner not predicted by the ancestral exposure or the proximate effects of stress during adolescence, an interaction we refer to as synchronicity.
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Male and female rats differ in their basal concentrations of corticosterone.
“male and female rats differ in their basal concentrations of corticosterone (Kitay, 1961; Gillette et al., 2014)”
From The effects of prenatal PCBs on adult social behavior in rats (2015) · cites this paper as Gillette et al., 2014
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EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals
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“Adrenal weights were heavier in females than in males, consistent with observations of Richter (1956) and our previous work using a transgenerational EDC (vinclozolin) exposure and evaluation of F3 descendants (Gillette et al., 2014).”
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- Authors
- Gillette, R., Miller-Crews, I., Nilsson, E. E., Skinner, M. K., Gore, A. C., & Crews, D.
- Affiliations
- The University of Texas at Austin (US)
- Washington State University (US)
- Corresponding author
- Crews, David
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2014-10-01
- Volume
- 155
- Issue
- 10
- Pages
- 3853-3866
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC4164929
- OpenAlex
- W1997388146
- Cited by
- 62
- References
- 12
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 10 · 2017: 4 · 2016: 6 · 2015: 12 · 2014: 3
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01es020662-05)
- National Institute of Mental Health (R21MH068273)
- National Institute of Environmental Health Sciences (ES017538, ES020662, R01-ES020662, ES012974, R56ES020662, R01ES012974, R01ES023254, ES023254, R21ES017538)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- vinclozolin, transgenerational epigenetic inheritance, endocrine disruptors, stress reactivity, adolescent stress, sex differences, anxiety, social behavior, brain transcriptome, brain metabolism, developmental origins of health and disease, two-hit model
- MeSH terms
- Adaptation, Psychological, Animals, Female, Fungicides, Industrial, Male, Oxazoles, Pregnancy, Prenatal Exposure Delayed Effects, Sex Characteristics, Stress, Psychological, Rats, Sprague-Dawley, Rats, Endocrine Disruptors
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