Parental exposure 3-methylcholanthrene disturbed the enterohepatic circulation in F1 generation of mice

Qihao Xu1, Lingyu Hu1, Siqi Chen1

  • 1College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, Zhejiang, China.

Chemosphere
|August 4, 2021
PubMed

Insights

Environmental exposure to 3-methylcholanthrene (3 MC) significantly impacts female mice and their offspring, disrupting bile acid metabolism and gut barrier function. Male exposure showed no adverse effects.

Area of Science:

  • Environmental Health
  • Toxicology
  • Metabolism

Background:

  • 3-methylcholanthrene (3 MC) is a polycyclic aromatic hydrocarbon (PAH) linked to hepatic dysfunction.
  • Investigating the transgenerational effects of environmental toxins is crucial for public health.

Purpose of the Study:

  • To evaluate the effects of 3-methylcholanthrene (3 MC) exposure on hepatic function, bile acid (BA) metabolism, and gut barrier integrity in mice.
  • To determine if these effects are transgenerational and sex-specific.

Main Methods:

  • Adult male and female mice (F0) were fed 3 MC (0.5 mg/kg) for 6 weeks.
  • F0 mice were mated, and their offspring (F1) were assessed at 5 weeks (F1-5W).
  • Assessed serum/fecal/liver total bile acids (TBAs), gene expression of BA-related and inflammation genes, and intestinal barrier markers.

Main Results:

  • 3 MC exposure decreased serum and fecal TBAs but increased liver TBAs in F0 females and F1-5W females from exposed mothers.
  • Altered gene expression related to BA metabolism and increased inflammation markers were observed.
  • Intestinal mucus secretion, tight junction proteins, ion transport, and antimicrobial peptides were disrupted in exposed females and offspring.

Conclusions:

  • Maternal 3 MC exposure, not paternal, disrupts bile acid metabolism and gut barrier function in a sex-specific manner.
  • Females are more susceptible to the adverse effects of 3 MC exposure.
  • These findings highlight potential risks of environmental PAHs on reproductive health and offspring development.

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