Thyroid Molecular Laboratory
Pathophysiology and Therapy of Metabolic and Endocrine Diseases
Hospital Universitario La Paz
DESCRIPTION OF THE OFFER
Gestational thyroid dysruption by halogenated phenolic xenobiotics: effects on thyroid, liver and developing brain in the Dehal1(-/-) murine model and in pregnant women.
During gestation, fetal brain development depends on maternal thyroid hormones (TH) supplied through the placenta. Thyroid function is a frequent target of endocrine disruption due to biochemical similarity of thyroid hormones and their precursors with halogenated phenolic xenobiotics, environmental pollutants derived from industrial production of plastics, pesticides and flame retardants.
The enzyme DEHAL1 deiodinates TH precursors MIT and DIT (halogenated mono-phenols) and recycles iodine in the thyroid, preventing hypothyroidism derived from iodine deficiency in risk populations such as pregnant women and children. Furthermore, DEHAL1 can debrominate and dechlorinate monophenols, at least in vitro. Besides in thyroid, the enzyme is also expressed in the liver, where its function is completely unknown.
This project investigates the existence of endocrine disruption of DEHAL1 function by xenobiotic compounds in vivo, using our mouse model Dehal1(-/-) (generated in the previous AES project) and in pregnant women. We seek to identify compounds with high risk for such disruption, know their molecular pathogenic mechanisms and determine their effects on fetal thyroid, brain and liver, and their impact on neurodevelopment.
Also investigate in vitro and in vivo the capacity of the DEHAL1 liver isoform to detoxify organo-halogenated (brominated/chlorinated bisphenols and diphenyl-esters) in a “phase II-like” enzyme activity and their functional relationship with Nrf2, the major regulator of catabolism of xenobiotic catabolism and oxidative stress responses in liver and brain.
Cristian González Guerrero
Jose Carlos Moreno Navarro