Exposition aux perturbateurs endocriniens et descendance

Le projet de recherche SPEPI fait suite à des travaux ayant montré des effets délétères dans plusieurs organes et tissus de la génération non exposée issue de rats mâles exposés de la conception à l'âge adulte à plusieurs perturbateurs endocriniens, seuls ou associés à des doses pertinentes par rapport aux expositions humaines. L'hypothèse de travail est que les spermatozoïdes des mâles exposés sont le "vecteur" des anomalies observées en seconde génération - l'état des connaissances actuelles suggérant que les effets observés pourraient résulter d’une dérégulation épigénétique

Genomic imprinting of the type 3 thyroid hormone deiodinase gene: Regulation and developmental implications

BACKGROUND: In recent years, findings in a number of animal and human models have ignited renewed interest in the type 3 deiodinase (D3), the main enzyme responsible for the inactivation of thyroid hormones. The induction of D3 in models of illness and injury has raised critical questions about the physiological significance of reduced thyroid hormone availability in those states. Phenotypes in transgenic mice lacking this enzyme also point to important developmental roles for D3. A critical determinant of D3 expression is genomic imprinting, an epigenetic phenomenon that regulates a small number of dosage-critical genes in the mammalian genome. The D3 gene (Dio3) is imprinted and preferentially expressed from one of the alleles in most tissues. SCOPE OF REVIEW: In the context of the physiological significance of D3 and the characteristics and purported origins of genomic imprinting, we review the current knowledge about the epigenetic mechanisms specifying gene dosage in the Dio3 locus. MAJOR CONCLUSIONS: Altered Dio3 dosage is detrimental to development, suggesting that the level of thyroid hormone action needs to be exquisitely tailored in a timely fashion to the requirements of particular tissues. An appropriate Dio3 dosage is the result of the coordinated action of certain genomic elements and epigenetic marks in the Dlk1-Dio3 domain. GENERAL SIGNIFICANCE: The imprinting of Dio3 prompts intriguing questions about why the level of thyroid hormone signaling should be regulated in this rare epigenetic manner, and to what extent altered Dio3 expression due to aberrant imprinting may be implicated in human conditions. This article is part of a Special Issue entitled Thyroid hormone signalling