Impact of iodine excess exposure during pregnancy and/or lactation on the hypothalamus-pituitary-thyroid axis activity in rat dams and their offspring

Abstract

Iodine is essential for thyroid hormones synthesis and an important regulator of thyroid function. Both iodine deficiency and excess promote alterations on thyroid function, which can cause serious consequences for individuals, especially during fetal and neonatal periods. Although there are many controversial results, some studies have shown that pregnant women undergoing rich iodine diet generated newborns with goiter and cognitive impairment, probably due to hypothyroidism. Intrauterine and lactation periods are important phases of the development in which hormonal, neuronal and nutritional disturbances may influence gene expression programming in adulthood, through epigenetic mechanisms. Therefore, this study aims to investigate the consequences of iodide excess during pregnancy and lactation periods on the hypothalamus-pituitary-thyroid (HPT) axis of pregnant rats and their offspring, after weaning (21 days) and in adult life (75 days). The animals will be treated with iodide excess (5X, 50X and 100X the physiological dose) throughout pregnancy and/or lactation. After these treatments, the hypothalamus, pituitary, thyroid and other tissues of the dams and their male offspring (21 and 75 days) will be used in: immunohistochemistry assays, Real-Time PCR and Western Blotting analysis of genes involved in the HPT axis activity, analysis of ROS and pro-inflammatory cytokines production. Moreover, we will also evaluate if iodide excess is able to program the offspring gene expression through epigenetic mechanisms, as DNA methylation, posttranslational modifications of histones and miRNAs expression. This evaluation is original and innovative, and certainly will contribute and clarify the molecular basis involved in the iodide excess effects in critical periods of development.