Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood

Sci Rep. 2020 Jul 2;10(1):10902. doi: 10.1038/s41598-020-67709-9.

Abstract

Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or through the microbiome-gut-brain axis. To test this hypothesis, California mice (Peromyscus californicus) offspring were exposed through the maternal diet to GEN (250 mg/kg feed weight) or BPA (5 mg/kg feed weight, low dose- LD or 50 mg/kg, upper dose-UD), and dams were placed on these diets two weeks prior to breeding, throughout gestation, and lactation. Various behaviors, gut microbiota, and fecal metabolome were assessed at 90 days of age. The LD but not UD of BPA exposure resulted in individuals spending more time engaging in repetitive behaviors. GEN exposed individuals were more likely to exhibit such behaviors and showed socio-communicative disturbances. BPA and GEN exposed females had increased number of metabolites involved in carbohydrate metabolism and synthesis. Males exposed to BPA or GEN showed alterations in lysine degradation and phenylalanine and tyrosine metabolism. Current findings indicate cause for concern that developmental exposure to BPA or GEN might affect the microbiome-gut-brain axis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Autism Spectrum Disorder / chemically induced
  • Bacteria / drug effects
  • Bacteria / isolation & purification
  • Benzhydryl Compounds / toxicity*
  • Brain / drug effects*
  • Brain / embryology
  • Brain / growth & development
  • Diet
  • Disease Models, Animal
  • Dysbiosis / chemically induced*
  • Endocrine Disruptors / toxicity*
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Genistein / toxicity*
  • Lactation
  • Male
  • Maze Learning
  • Memory Disorders / chemically induced
  • Metabolome / drug effects
  • Peromyscus / embryology
  • Peromyscus / growth & development
  • Peromyscus / metabolism
  • Peromyscus / microbiology*
  • Phenols / toxicity*
  • Preconception Injuries / chemically induced
  • Pregnancy
  • Pregnancy Complications / chemically induced
  • Pregnancy Complications / microbiology
  • Prenatal Exposure Delayed Effects*
  • Social Behavior
  • Species Specificity
  • Vocalization, Animal

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • Genistein
  • bisphenol A