In vitro endocrine modulation within the Hypothalamus-Pituitary-Ovary (HPO) axis: by dioxin like compounds and phytoestrogens

Abstract

There is a wide range of alternative cellular test systems available, with the majority being derived from relevant organs and tissues that are frequently derived from human origin or embryonic life stages. Nevertheless, in vitro modeling of the full reproductive cycle to predict human reproductive and developmental risk remains a monumental challenge. The aim of this thesis was to study alterations by endocrine disrupting compounds (EDCs) in (part of) the hypothalamus-pituitary-ovary (HPO)-axis using some available in vitro cell models. The main focus was on mechanisms of action of EDCs upon neuroendocrine and steroid hormone modulations. To this purpose, several cells of hypothalamic, pituitary or ovary origin were used and evaluated for their value in determining EDC- responsive biomarkers of HPO-axis. To achieve this purpose, molecular indicators of endocrine modulation at the level of the hypothalamus, pituitary and ovary level were studied. As a result, this PhD thesis provides some interesting cell models, which could support future identification and elucidation of the modes and mechanisms of action of dioxins and phytoestrogens within the HPO-axis.