Exposure to di-(2-ethylhexyl) phthalate transgenerationally alters anxiety-like behavior and amygdala gene expression in adult male and female mice

Katherine M. Hatcher, Jari Willing, Catheryne Chiang, Saniya Rattan, Jodi A Flaws, Megan M Mahoney

Research output: Contribution to journalArticle

Abstract

Phthalates are industrial plasticizers and stabilizers commonly found in polyvinyl chloride plastic and consumer products, including food packaging, cosmetics, medical devices, and children's toys. Di-(2-ethylhexyl) phthalate (DEHP), one of the most commonly used phthalates, exhibits endocrine-disrupting characteristics and direct exposure leads to reproductive deficits and abnormalities in anxiety-related behaviors. Importantly, increasing evidence indicates that the impacts of DEHP exposure on reproduction and social behavior persist across multiple generations. In this study, we tested the hypothesis that transgenerational DEHP exposure alters anxiety-like behavior and neural gene expression in both male and female mice. Pregnant CD-1 mice were orally dosed daily with either tocopherol-stripped corn oil or DEHP (20 or 200 μg/kg/day; 500 or 750 mg/kg/day) from gestational day 10.5 until birth to produce the F1 generation. Females from each generation were bred with untreated, unrelated CD-1 males to produce subsequent generations. Behavior and gene expression assays were performed with adult, intact F3 males and females. Transgenerational DEHP exposure increased time spent in the open arm in the elevated plus maze for adult females (750 mg/kg/day lineage), but not males. In adult females, we observed a down-regulation of mRNA expression of estrogen receptor 1 in the 200 μg/kg/day and 500 mg/kg/day treatment lineages, mineralocorticoid receptor in the 200 μg/kg/day lineage, and dopamine receptor 2 in the 20 μg/kg/day and 750 mg/kg/day lineages. In adult males, we found an up-regulation of estrogen receptor 2 in the 20 and 200 μg/kg/day lineages, and dopamine receptor 1 in the 20 μg/kg/day and 750 mg/kg/day lineages. No hippocampal gene expression modifications were observed in response to treatment. These results implicate dose-specific transgenerational effects on behavior and neural gene expression in adult male and female mice.

Original languageEnglish (US)
Pages (from-to)7-14
Number of pages8
JournalPhysiology and Behavior
Volume207
DOIs
StatePublished - Aug 1 2019

Fingerprint

Amygdala
Anxiety
Gene Expression
Dopamine Receptors
Food Packaging
Plasticizers
Mineralocorticoid Receptors
Estrogen Receptor beta
Play and Playthings
Corn Oil
Tocopherols
Estrogen Receptor alpha
Social Behavior
phthalic acid
Polyvinyl Chloride
Cosmetics
Plastics
Reproduction
Up-Regulation
Down-Regulation

Keywords

  • Elevated plus maze
  • Endocrine disrupting chemicals
  • F3 generation
  • Plasticizers
  • Transgenerational

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience

Cite this

Exposure to di-(2-ethylhexyl) phthalate transgenerationally alters anxiety-like behavior and amygdala gene expression in adult male and female mice. / Hatcher, Katherine M.; Willing, Jari; Chiang, Catheryne; Rattan, Saniya; Flaws, Jodi A; Mahoney, Megan M.

In: Physiology and Behavior, Vol. 207, 01.08.2019, p. 7-14.

Research output: Contribution to journalArticle

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