Thesis: Éloïse Giabicani – Growth and insulin-like growth factors (IGF): physiopathology insights from imprinting diseases
July 01 - 2019
directed by Irène Netchine
Abstract: Fetal growth is dependent on many environmental, genetic and hormonal factors whose interactions will condition its proper development. The insulin-like growth factors (IGFs) system plays a major role at the interface of these different factors to ensure good fetal growth. In this work, we have focused on the different actors of the IGF system in fetal growth pathologies. In a clinical and experimental approach, we described the functional consequences of genetic or epigenetic abnormalities of interest to IGF-I, IGF-II and their common IGF1R receptor. For example, we have developed a functional test to assess the in vitro activity of IGF1R in patients with fetal and postnatal growth restriction. We have also documented the bioavailability of IGF-I in patients with Silver-Russell syndrome, which is a pathology related to the parental imprint responsible for ante-natal onset growth restriction. Finally, we characterized the clinical and molecular overlap between patients with SRS or Temple syndrome (other pathology related to parental imprinting), confirming the predominant role of IGF2 expression failure in these two syndromes. These results confirm the functioning of networked imprinted genes and the major role of the IGF system in fetal growth, particularly altered in the event of pathology affecting these imprinted genes.
Keywords: fetal growth, IGF system, parental imprint, multiple methylation abnormalities, network of genes subject to parental imprinting, IGF-I, IGF2, IGF1R.