title: Sexually dimorphic effects of ancestral exposure to vinclozolin on stress reactivity in rats.
abstract: 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.
authors: Institute for Cellular and Molecular Biology (R.G., I.M.-C., A.C.G., D.C.), Division of Pharmacology and Toxicology (A.C.G., D.C.), and Department of Integrative Biology (D.C.), The University of Texas at Austin, Austin, Texas 78712; and Center for Reproductive Biology (E.E.N., M.K.S.), School of Biological Sciences, Washington State University, Pullman, Washington 99164.
authors: Ross
authors: R
authors: Gillette
authors: Isaac
authors: I
authors: Miller-Crews
authors: Eric E
authors: EE
authors: Nilsson
authors: Michael K
authors: MK
authors: Skinner
authors: Andrea C
authors: AC
authors: Gore
authors: David
authors: D
authors: Crews
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects*; D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D008297:Male; D010080:Oxazoles / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D052244:Endocrine Disruptors; D005659:Fungicides, Industrial; D010080:Oxazoles; C025643:vinclozolin