Impact of maternal exposure to triclosan during pregnancy in the hypothalamus-pituitary-thyroid axis activity of the offspring

Abstract

Endocrine disruptors are synthetic or natural compounds that negatively affects the endocrine system function. Triclosan (TCS) is an antimicrobial chemical used in several products, as personal care products, food, pesticides, plastics, rubbers and industrial additive. TCS is widely found in the environment, and it has already been found in breast milk, plasma and urine samples of humans. Studies have related TCS exposure to endocrine dysfunctions, including thyroid function abnormalities. Indeed, TCS exposure is commonly associated with the decrease of T4 levels in humans and other animals. In rats, the maternal exposure to TCS has been related to reduced levels of T4 in the rat dams, and deleterious effects in the offspring, as low weight at birth and altered reproductive structures. However, the effects and the mechanisms triggered by TCS in the thyroid function of the offspring are still unknown. Thus, the main objective of this project is to investigate the impact of maternal exposure to TCS during pregnancy in the development and function of the hypothalamus-pituitary-thyroid axis of the offspring rats in different stages of life. For this purpose, pregnant Wistar rats will be treated or not (control group) with TCS (10 or 30 mg/kg/day) diluted in corn oil during pregnancy. The offspring rats (males and females) will be analyzed in two different periods: at gestational day 20th (GD20) and in adult life (90th postnatal day- PND90). At these specific periods, the offspring rats will be euthanized, and the hypothalamus, pituitary, thyroid, liver and kidney will be collected for molecular analysis. Gene and protein expression will be evaluated by RT-qPCR and Western Blot. The participation of epigenetic mechanisms in the programming of thyrocytes gene expression will also be investigated. The results obtained in this study will certainly elucidate the molecular mechanisms by which TCS interferes with the function of the thyroid gland, whose hormones act in several tissues and organs in the organism. The data will also contribute to determine the safe dose of exposure to TCS during critical periods of development.