Impact of intrauterine exposure to PCBs on embryonic thyroid development and programming of the hypothalamus-pituitary-thyroid axis of the offspring animals

Abstract

PCBs (polychlorinated biphenyls) are flame retardant compounds widely used as lubricants in the industry and in several electronic devices. The use of PCBs was banned over 25 years ago, however, they are highly persistent in the environment and remain in the food chain until this day. PCBs are lipophilic, concentrate in the adipose tissue and serum, and their biological half-life in humans is approximately 7 years. Their chemical structure is similar to that of THs and, therefore, they bind to the receptors of these hormones. Rodent exposure to PCBs has previously been associated with low serum T4 levels. However, the data on the effects of PCBs on hypothalamic-pituitary-thyroid axis function in humans are still controversial. Nevertheless, studies have reported a correlation between prenatal exposure to PCBs and cognitive impairment in children. Thus, the molecular effects of this endocrine disruptor on the thyroid gland and its effects on fetal thyroid development need to be clarified. The main objective of the present study will be to investigate the consequences and molecular mechanisms triggered by maternal exposure to PCBs during pregnancy on the function of the hypothalamus-pituitary-thyroid axis at different stages of development - at birth and during adulthood. Therefore, pregnant Wistar rats will be treated with 5 or 50 ¼g of A1254/kg/day during the gestation period. The offspring (males and females) will be analyzed in two different periods: on the 20th day of gestation (GD20) and during adulthood (PND90). Hypothalamus, pituitary, thyroid, liver and kidney will be collected for analysis of gene and protein expression by RT-qPCR and Western Blotting, respectively. If significant alterations are observed in thyroid gene expression, additional studies will be performed to assess whether intrauterine exposure to PCBs programs the thyroid of the offspring animals, through epigenetic mechanisms, such as DNA methylation, post-translational alterations of histones and/or differential expression of miRNAs. This study will add new data about the molecular basis involved in the regulation of the hypothalamic-pituitary-thyroid axis function and programming by PCBs at a critical period of development.