Maternal procymidone exposure has lasting effects on murine gut-liver axis and glucolipid metabolism in offspring.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association(2023)

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摘要
There is increasing evidence that maternal exposure to environmental pollutants can cause intestinal and metabolic diseases, and these disease risks still exist in offspring. Here, female C57BL/6 mice were orally treated with procymidone (PRO) (10 and 100 mg/kg body weight/day) by dietary supplementation during the gestation and lactation periods. Then, we discovered PRO changed the physiology, intestinal barrier and metabolism both in the generations of F and different developmental stages of F (7 weeks and 30 weeks old, respectively). Maternal PRO exposure affected the growth phenotypes and the glucolipid metabolism related indicators and genes of mice, especially the male mice of F generations. The changes in bile acids (BAs) metabolism demonstrated that PRO disordered glucolipid metabolism through enterohepatic circulation. Furthermore, PRO reduced mucus secretion in the gut and altered the composition of gut microbiota, leading more bacteria to disseminate in the gut and inflammatory responses both in F and F regenerations. And PRO-induced gut microbiota dysbiosis was tightly related to BAs metabolites. Together, the results indicated that PRO destructed the functional integrity of intestinal barrier and the inflammatory reaction was triggered. And then, the disorder of glucolipid metabolism was induced through the BAs enterohepatic circulation. This study indicated that the cross-generation effects of PRO could not be ignored.
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关键词
Bile acid,Glucolipid metabolism,Intestinal barrier,Mice,Procymidone
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