Impact of maternal exposure to perchlorate during pregnancy in the hypothalamus-pituitary-thyroid axis activity of rat dams and their offspring

Abstract

Perchlorate is a widespread contaminant present in irrigation water, soil and food. This anion inhibits the iodide uptake mediated by the sodium-iodide symporter (NIS) in thyrocytes. Several studies have shown that besides its inhibitory action, perchlorate is also transported by NIS in the thyroid cells. Therefore, this anion interferes with the thyroid hormone synthesis and impairs the thyroid function. The deleterious effects of perchlorate in the thyroid function are especially described in populations with deficient iodine diet. Even though, the effects of perchlorate exposure are poorly described in critical periods of the development, as pregnancy and lactation. In fact, the harmful effects of perchlorate exposure to maternal thyroid function are still controversial. However, it has been suggested that the fetus is more susceptible to the deleterious and inhibitory effects of perchlorate exposure in the thyroid gland. Since the thyroid hormones are important to the adequate embryonic development and that poor intrauterine environment is involved in the programming of diseases during adult life, the main objective of this study is to investigate the consequences of maternal exposure to perchlorate during the gestation in the activity of the hypothalamus-pituitary-thyroid (HPT) axis of the rat dams and their offspring. For this purpose, pregnant rats will be treated or not with water supplemented with NaClO4 (0.2 or 1 mg/L) during the gestation period. After the birth of the offspring, the rat dams will be maintained with rat chow and filtered water ad libitum. At the end of the weaning, the offspring rats will also be maintained with chow and filtered water until the post-natal day 90 (PND90). The hypothalamus, pituitary and thyroid of the rat dams and their offspring will be used in assays to analyze the expression of genes and proteins involved in the activity of the HPT axis. Additional studies will be performed to evaluate the effect of perchlorate exposure in the programing of thyroid gene expression through epigenetic mechanisms. Therefore, global DNA methylation and post-translational alterations in the histones will also be investigated. The results of this project will certainly contribute to the comprehension of the molecular mechanisms triggered by perchlorate during a critical period of the development and its potential effect as an endocrine disruptor of the thyroid function.