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Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
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.
Abstract:
3-methylcholanthrene (3 MC) is an environmental compound belonging to the PAHs and is reportedly thought to be a risk factor for the prevalence of hepatic function disorder. Here, a dose of 0.5 mg/kg of 3 MC was given to 4-week-old male and female mice (F0) in their diet for 6 weeks. After exposure, then the mice were mated between different groups. The first filial (F1) generation offspring of exposed or unexposed parental mice were sacrificed at the age of 5 weeks (F1-5 W), and the potential effects on the F0 and F1 offspring were evaluated. The results showed that the total bile acids (TBAs) in the serum and feces in F0 females and female F1-5 W individuals born from female mice exposed to 3 MC decreased, while the TBAs in the liver increased. The transcriptional levels of major genes participating in synthesis, regulation, transportation and apical uptake was also altered correspondingly. In addition, the transcription of some genes related to inflammation was enhanced in these mice. Further investigation revealed that in addition to distinct changes in the mucus secretion, tight junction proteins and ion transport were induced, and antimicrobial peptides were also disrupted in the intestine of F0 mice and F1-5 W female offspring of maternal mice exposed to 3 MC. Our results suggested that exposure to 3 MC, but not male exposure, had the potential to interfere with BAs metabolism, affecting gut barrier function. Females were more seriously affected than males.
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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