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The results of this study are one of the clearest evidence to date, suggesting that genetic and environmental factors may combine to interfere with neurodevelopment
Compared with traditional animal research, the use of brain organoids in this research also points out the direction for faster, cheaper, and more human-related experiments in this field
The brain organoid model developed by researchers at Bloomberg School is composed of cell spheres that are differentiated from the culture of human stem cells to mimic the developing human brain
This study was published online on July 14 in the journal Environmental Health Perspectives.
"This is a step forward in showing the interaction between genetics and the environment and its potential effect on autism spectrum disorders," said Dr.
According to the Centers for Disease Control and Prevention (Centers for Disease Control and Prevention) data, autism spectrum disorders were rare 40 years ago, and now about 2% of live births have autism
In recent decades, "the increase in diagnosis of autism is difficult to explain.
How environmental factors and genetic susceptibility interact to increase the risk of autism spectrum disorder is still largely unknown, partly because these interactions have been difficult to study
Advances in stem cell research methods over the past few decades have allowed researchers to use human skin cells, which can be transformed into stem cells and then into almost any type of cell for research in the laboratory
In their study, the researchers used brain organoids to simulate the effects of CHD8 gene disruption and exposure to chlorpyrifos
Smirnova said: "High-dose, short-term experimental exposures do not reflect the real situation, but they provide us with a starting point to identify genetic variants that may make individuals more susceptible to toxic substances
The researchers found that the CHD8 protein level in brain organoid cells with only one copy of the CHD8 gene was only two-thirds of the normal level, but chlorpyrifos exposure made CHD8 levels much lower, turning moderate deprivation into severe deprivation
As part of their research, the researchers compiled a list of molecules in blood, urine, and brain tissue that have shown differences in autistic patients in previous studies
"In this sense, we found that changes in these organoids reflect changes in patients with autism," Smirnova said
According to the researchers, these findings paved the way for further studies of gene-environment interactions in diseases using organoids of human origin
Hartung said: "Using a three-dimensional, human-derived, brain-like model, like the model in this study, is a great way to study the interaction of genetic and environmental factors in autism and other neurodevelopmental disorders.
Original Search: Sergio Modafferi, Xiali Zhong, Andre Kleensang, Yohei Murata, Francesca Fagiani, David Pamies, Helena T.
Hogberg, Vittorio Calabrese, Herbert Lachman, Thomas Hartung, Lena Smirnova.
Gene–Environment Interactions in Developmental Neurotoxicity: a Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres .
Environmental Health Perspectives , July 14, 2021; DOI: 10.
1289/EHP8580