Impact of endocrine disruptors from mother's diet on immuno-hormonal orchestration of brain development and introduction of the virtual human twin tool.

Abstract

Diet has long been known to modify physiology during development and adulthood. However, due to a growing number of manufactured contaminants and additives over the last few decades, diet has increasingly become a source of exposure to chemicals that has been associated with adverse health risks. Sources of food contaminants include the environment, crops treated with agrochemicals, inappropriate storage (e.g., mycotoxins) and migration of xenobiotics from food packaging and food production equipment. Hence, consumers are exposed to a mixture of xenobiotics, some of which are endocrine disruptors (EDs). The complex interactions between immune function and brain development and their orchestration by steroid hormones are insufficiently understood in human populations, and little is known about the impact on immune-brain interactions by transplacental fetal exposure to EDs via maternal diet. To help to identify the key data gaps, this paper aims to present (a) how transplacental EDs modify immune system and brain development, and (b) how these mechanisms may correlate with diseases such as autism and disturbances of lateral brain development. Attention is given to disturbances of the subplate, a transient structure of crucial significance in brain development. Additionally, we describe cutting edge approaches to investigate the developmental neurotoxicity of EDs, such as the application of artificial intelligence and comprehensive modelling. In the future, highly complex investigations will be performed using virtual brain models constructed using sophisticated multi-physics/multi-scale modelling strategies based on patient and synthetic data, which will enable a greater understanding of healthy or disturbed brain development.