Fetal Bisphenol-A Induced Changes in Murine Behavior and Brain Gene Expression Persisted in Adult-aged Offspring

Endocrinology. 2020 Dec 1;161(12):bqaa164. doi: 10.1210/endocr/bqaa164.

Abstract

In utero Bisphenol A (BPA) exposure has been linked to many deficits during brain development, including sexual differentiation, behavior, and motor coordination. Yet, how BPA induces these disorders and whether its effects are long lasting are largely unknown. In this study, using a mouse model, we demonstrated that in utero exposure to an environmentally relevant dose of BPA induced locomotor deficits, anxiety-like behavior, and declarative memory impairments that persisted into old age (18 months). Compared to the control animals, the BPA-exposed mice had a significant decrease in locomotor activity, exploratory tendencies, and long-term memory, and an increase in anxiety. The global brain gene expression profile was altered permanently by BPA treatment and showed regional and sexual differences. The BPA-treated male mice had more changes in the hippocampus, while female mice experienced more changes in the cortex. Overall, we demonstrate that in utero exposure to BPA induces permanent changes in brain gene expression in a region-specific and sex-specific manner, including a significant decrease in locomotor activity, learning ability, long-term memory, and an increase in anxiety. Fetal/early life exposures permanently affect neurobehavioral functions that deteriorate with age; BPA exposure may compound the effects of aging.

Keywords: bisphenol A; in utero; locomotor; memory; neurobehavioral disorder.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Benzhydryl Compounds / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism
  • Endocrine Disruptors / pharmacology*
  • Estrogens, Non-Steroidal / pharmacology*
  • Exploratory Behavior / drug effects
  • Female
  • Gene Expression / drug effects*
  • Male
  • Maze Learning / drug effects
  • Mice
  • Motor Activity / drug effects
  • Phenols / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / genetics*
  • Prenatal Exposure Delayed Effects / metabolism
  • Recognition, Psychology / drug effects
  • Sex Factors

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Estrogens, Non-Steroidal
  • Phenols
  • bisphenol A