Cross-generational effects of maternal exposure to imazalil on anaerobic components and carnitine absorption associated with OCTN2 expression in mice

Abstract

Imazalil (IMZ) is a fungicide recommended by the Chinese ministry of agriculture. However, recent study was observed high level of IMZ by dietary exposure in pregnant women. To determine the cross-generational effects, C57BL/6 mice were exposed to IMZ at dietary levels of 0, 0.025‰, and 0.25‰ during the gestation and lactation periods. Then, we assessed the changes in growth phenotypes, carnitine levels, and gut microbiota in F0, F1 or F2 generations. The growth phenotypes of dams didn't observe significant difference, but there were significant changes in the offspring. Plasma samples revealed low levels of free carnitine (C0), long-chain acyl-carnitines and total carnitine. In particular, C0 may be regarded as relatively potential, specific markers by maternal IMZ exposure. Caco2 cell culture and animal experiment confirmed IMZ affected carnitine absorption through the organic cation transporter type-2 (OCTN2) protein encoded by solute carrier family 22A member 5 (SLC22A5) gene in colon. Maternal IMZ exposure also had a greater effect on gut microbiota in offspring, especially anaerobic bacteria, which positively correlated with C0 and acyl-carnitines. These results suggested that maternal IMZ exposure affected carnitine absorption through OCTN2 protein, which led to the decline of anaerobic bacteria and unbalanced intestinal homeostasis.