title: Transgenerational Effects of Di-(2-Ethylhexyl) Phthalate (DEHP) on Stress Hormones and Behavior.
abstract: Exposure to di-(2-ethylhexyl) phthalate (DEHP) has been linked to male reproductive abnormalities. Here, we assessed transgenerational actions of DEHP on several behaviors and stress responses. We used 2 doses of DEHP (150- and 200-mg/kg body weight) and a treatment regimen previously shown to produce transgenerational effects on male reproduction. Mice, 3 generations removed from DEHP exposure (F3), were tested for social behavior and anxiety on the elevated plus maze. We collected blood and pituitaries from undisturbed and restrained mice. Body weights, anogenital distances, and reproductive organ weights were collected at killing. In social interaction tests juvenile males from the DEHP lineage (200 mg/kg) displayed more digging and less self-grooming than did controls. Interestingly, 150-mg/kg lineage males, killed in early puberty, had smaller seminal vesicle weights than their controls. However, the 200-mg/kg males (killed on average 10 d later) did not show this effect. Females from a DEHP lineage had lower corticosterone concentrations than controls after restraint stress. We also found sex- and DEHP-specific mRNA expression changes in the pituitary in 2 of the 6 stress-related genes we measured. In particular, Gnas mRNA was elevated by the combination of DEHP lineage and stress. Thus, transgenerational effects of DEHP are noted in male behavior, and in females, DEHP had transgenerational effects on levels of corticosterone. Both of these results may be related to transgenerational modifications in the expression of several pituitary hormones involved in the hypothalamic-pituitary-adrenal axis.
authors.affiliation: Neuroscience Graduate Program and Department of Biochemistry and Molecular Genetics (K.M.Q., E.F.R.), University of Virginia School of Medicine, Charlottesville, Virginia 22903; and School of Molecular Biosciences (T.J.D., K.H.K.), College of Veterinary Medicine, Washington State University, Pullman, Washington 99164.
authors.forename: Kayla M
authors.initials: KM
authors.lastname: Quinnies
authors.affiliation: Neuroscience Graduate Program and Department of Biochemistry and Molecular Genetics (K.M.Q., E.F.R.), University of Virginia School of Medicine, Charlottesville, Virginia 22903; and School of Molecular Biosciences (T.J.D., K.H.K.), College of Veterinary Medicine, Washington State University, Pullman, Washington 99164.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Doyle
authors.affiliation: Neuroscience Graduate Program and Department of Biochemistry and Molecular Genetics (K.M.Q., E.F.R.), University of Virginia School of Medicine, Charlottesville, Virginia 22903; and School of Molecular Biosciences (T.J.D., K.H.K.), College of Veterinary Medicine, Washington State University, Pullman, Washington 99164.
authors.forename: Kwan Hee
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Neuroscience Graduate Program and Department of Biochemistry and Molecular Genetics (K.M.Q., E.F.R.), University of Virginia School of Medicine, Charlottesville, Virginia 22903; and School of Molecular Biosciences (T.J.D., K.H.K.), College of Veterinary Medicine, Washington State University, Pullman, Washington 99164.
authors.forename: Emilie F
authors.initials: EF
authors.lastname: Rissman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005260:Female; D005835:Genitalia / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D013315:Stress, Psychological / Q000097:blood* / Q000139:chemically induced
chemical_list: D004051:Diethylhexyl Phthalate; D003345:Corticosterone