Investigation of the Potential Mechanism of Maternal Iodine Excess or Iodine Deficiency on Offspring via Untargeted Metabolomics

Abstract

Background: Iodine plays a key role in various functions of the central nervous system, and both iodine deficiency and excess are harmful to health. This study aimed to explore the potential metabolites and pathways involved in the effects of excess maternal iodine or iodine deficiency on offspring. Methods: All female rats were randomly grouped into severe iodine deficiency (SID), mild iodine deficiency (MID), normal iodine (NI), mild iodine excess (MIE), and severe iodine excess (SIE), and the corresponding model was constructed based on the water iodine intervention. After successful conception, the same feeding conditions were maintained for the pregnant rats. On the 21st day of pregnancy, serum samples of the offspring were collected for liquid chromatography-tandem mass spectrometry and bioinformatics analyses. Results: With the increase in the iodine intervention dose, the median urinary iodine of rats, as well as their free thyroxine levels and positive rate of thyroglobulin antibody, were also elevated (p < 0.05), suggesting that the model was successfully constructed. By analyzing the serum metabolites of offspring, 173, 186, 66, and 92 differential metabolites, such as L-glutamic acid and deoxycytidine, were found to be significantly altered in the severe iodine deficiency SID vs. the normal iodine, the mild iodine deficiency vs. the normal iodine, the mild iodine excess vs. the normal iodine, and the severe iodine excess vs. the normal iodine groups, respectively. Pathway enrichment analysis revealed that ATP-binding cassette (ABC) transporters were the most commonly enriched metabolic pathways. Conclusion: These findings suggest that maternal iodine deficiency or excess may affect the development of offspring by regulating metabolites such as L-glutamic acid and deoxycytidine via the ABC transporter pathway.