Endocrine Abstracts

During vertebrate evolution thyroid hormone acquired multiple roles in development, especially brain development. Examples include promotion of myelination thereby increasing speed of neuronal transmission, as well as modulation of neuronal differentiation, as exemplified by the exquisite sensitivity of the Purkinje neuron to thyroid hormone deficiency. Research in the last 15 years has demonstrated that early development, the first trimester of pregnancy in humans, is an unexpectedly thyroid- hormone dependent period. In the same time span we have witnessed an unprecedented increase in autism spectrum disorders (ASD) incidence, correlated in many data sets with loss of IQ. Although, changes in diagnosis and awareness can contribute the ASD increase, many authors consider that environmental factors, possibly exacerbating genetic susceptibilities, are implicated. Four main arguments support this hypothesis. First, increasing numbers of chemicals are found routinely in human amniotic fluid. These include, pesticides, plasticizers (such as phthalates, BPA), nitrates, perchlorate, antimicrobials (such as Triclosan), flame-retardants, surfactants and mercury (produced by fossil fuel burning). Second, many of these chemical categories can interfere with thyroid hormone signalling, a pathway essential for orchestrating brain development. Third, prenatal exposure to many chemicals is significantly associated with both IQ loss and increased ASD risk. Fourth, production of many of these chemicals has risen exponentially in the last few decades, continually increasing exposure. The cost of exposure in socio-economic terms has been estimated for just two or three chemicals to be in the order of 150 billion Euros per annum for Europe. I will present and discuss data showing that cocktails of these chemicals found in amniotic fluid can interfere with thyroid hormone signalling and brain development, affecting genes and developmental pathways (neuronal proliferation, migration) that are regularly associated with brain development and with ASD.