Novel chemical tests could safeguard foetal health
Endocrine disruptors (EDCs) are chemicals that can adversely interfere with hormone systems by mimicking hormones or blocking their normal action. They are typically found in plastics, pesticides and flame retardants, leaking into the environment and food chain and accumulating in the human body. One critical area of study is how EDCs can impair hormone-dependent development already in utero, as well as during sensitive periods such as neonatal development.
Chemicals with EDC characteristics
The EU-funded ATHENA(opens in new window) project focused on this field, and in particular on the production and local supply of thyroid hormone. This plays a crucial role in regulating the body’s metabolism and growth, among other functions. During the first few weeks of gestation, the foetus is unable to produce thyroid hormone and relies on maternal supply. It is known that EDCs in the maternal system can decrease circulating thyroid hormone, changing the levels that reach the foetus. “Maternal thyroid hormone delivery to the foetal brain via the placental barrier is of eminent importance especially during the first trimester,” says ATHENA project member Martin Scholze from Brunel University(opens in new window) in the United Kingdom. “EDC disturbance of this process can result in irreversible deficits throughout adult life.” Knowledge gaps still exist regarding the details of the molecular mechanisms and functional protein components involved in this process. It is these knowledge gaps that the ATHENA project sought to address, through developing new experimental models and test methods. “A combined approach involving in silico, in vitro, animal experimental ex vivo and human epidemiological methods was developed,” ATHENA project member Josef Köhrle from Charité-University Medicine(opens in new window), Berlin, Germany, explains. “These approaches were validated and applied to identify relevant EDC exposure scenarios.” This work enabled the project team to identify potential new methods for identifying chemicals with EDC characteristics that might adversely affect the developing thyroid hormone system.
Multistep test strategy for identifying EDCs
The project has made important advances in the identification of human-relevant EDC exposure, with a specific focus on thyroid hormone-related maternal-foetal health during pregnancy. A multistep test strategy for identifying EDCs affecting the maternal-foetal thyroid hormone system during development has been developed and proposed. The project team also developed quantitative structure-activity relationships (QSARs) – mathematical models used to predict the biological properties of compounds from knowledge of their chemical structure – for the screening of large compound libraries. “We were also able to show that amitrole, a pesticide still present in our environment, is an EDC that can potentially cause brain structure malformation and behavioural impairments in the offspring of rats after maternal exposure during pregnancy and lactation,” adds Köhrle.
Predicting and identifying potential EDCs
The methods and techniques pioneered in ATHENA – as well as the knowledge gained – will help to establish standardised tests for predicting and identifying potential EDCs that can affect the thyroid hormone system during pregnancy. “These testing methods will now be further developed, with a view to regulatory acceptance,” says Scholze. Accumulated data has also shed new light on thyroid hormone-dependent foetal brain development across many vertebrate species, all of them essentially depending on adequate local thyroid hormone supply. These findings have helped to underline the consequences of maternal thyroid hormone deficiency for the developing brain due to EDCs.
Keywords
ATHENA, chemical, EDCs, endocrine disruptors, foetal, pregnancy, health