Journal
ENDOCRINOLOGY
Volume 156, Issue 9, Pages 3077-3083Publisher
ENDOCRINE SOC
DOI: 10.1210/EN.2015-1326
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Funding
- National Institutes of Health [R01 ES022759, R01 ES019836]
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Exposure to di-(2-ethylhexyl) phthalate (DEHP) has been linked to male reproductive abnormalities. Here, we assessed transgenerational actions of DEHP onseveral 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.
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