Endocrine disruptors vs. thyroid: an epigenetic analysis of the development, differentiation and function of thyrocytes and their repercussions on the organism

Abstract

Endocrine Disruptors (EDs) are synthetic or natural compounds that interfere with the endocrine system and induce harmful effects to the organism. Even though, these deleterious effects depend on the dose and the period of exposure to EDs. In fact, several studies indicated increased amounts of EDs in human samples as well as in the environment that are mainly associated to the extensive use of industrialized products. Previous studies suggested that bisphenol A, polyclorated biphenyls, triclosan, phthalates, organochlorine pesticides, perchlorate and nitrate could disrupt thyroid function, by their structural similarity to the Thyroid Hormones (TH) or by interfering with TH synthesis. It is worth noting that thyroid dysfunction is the second most prevalent endocrine disease in the world and its incidence has increased in the past few years. Since maternal thyroid function is essential for the fetal development and that the intra-uterine period is important for programming genes at adult life through epigenetic mechanisms, this study aims to investigate the consequences and the molecular mechanisms triggered by maternal exposure to EDs during pregnancy on the maternal thyroid function as well as on the differentiation, maturation and function of the offspring's thyroid at different periods of development. For this purpose several models will be used: in vivo (pregnant female mice), ex vivo (embryonic endoderm and thyroid explants) and in vitro (embryonic stem cells, induced pluripotent stem cells and thyroid cell lineages). Additionally, DNA methylation, histones post-translational modifications and the expression of miRNAs will be evaluated to determine whether the exposure to DEs programs thyrocytes gene expression through epigenetic mechanisms. This study is original, innovative and certainly will clarify the molecular basis involved in the EDs effects on the development and function of thyroid, whose hormones are extremely important to the organism. Finally, the results obtained in this study will enable the implementation of local and worldwide strategies of prevention and intervention for the most susceptible populations, i.e. pregnant women, fetuses and newborns. (AU)