We have published several studies in the past few years linking environmental toxins from air pollution to a variety of serious health consequences¹. Now, the results of a new study suggest that pregnant women exposed to air pollution toxins and stress may be linked to autism in their male children.
The study involved exposing pregnant mice to air pollution chemicals in the form of diesel exhaust particles. Next, towards the end of their pregnancy, the mice moms were dealt another stressor: they were given insufficient material from which to build a nest for their pups. According to the researchers, this added stress mimics the situation that many humans find themselves in during the course of their normal lives. The reason for adding the additional stress onto test subjects was to test this combination of conditions (air pollution exposure plus stress) in order to monitor the effects on the brain development of the offspring. The researchers argue such conditions are endured by many humans every day.
The results demonstrated that although the stressed mice were exemplary parents that nursed and groomed their pups just as much as those who were spared the prenatal stressors, their male offspring exhibited unusual, autism-like social behavior*. Adolescent male mice born to stress- and smog-exposed moms preferred hanging out with a yellow rubber duck rather than a nearby mouse (mice usually prefer the company of one of their own, rather than that of a bath toy). Female offspring were less likely to be affected in this way.
*Humans with autism are not inherently introverted, but rather, have difficulty understanding social cues and conventions rather than being unwilling to interact socially.
The researchers wondered what had happened in the brains of the male offspring that may have made them socially shy. More specifically, the research team wondered whether male brains had somehow missed out on their necessary refinement early in development. All young animals have an excess of connections (synapses) between their brain cells. As they grow up and develop, these connections get “pruned” back; connections that are used often are strengthened while connections that are seldom used are removed. The result of this process of synaptic pruning is that the brain becomes more efficient as the animal ages.
The results of the brain analysis of mice indicated that male offspring of stressed mothers who had inhaled diesel fumes had missed out on the normal pruning of synapses in the anterior cingulate cortex (ACC), a brain region that is important for perceiving and producing social cues. The overabundance of synapses in this region seemed to explain their shy social tendencies as teenagers, but it left open the question of how a double-hit of smog and stress during gestation halts typical brain sculpting.
In order to understand this, next the researchers examined the immune system. They focused their analysis on immune cells in the brain, called microglia. These are highly active cells that monitor the brain constantly for pathogens such as viruses and bacteria, but they also destroy weak or dead synapses. This helps to trim away unwanted connections and keep the brain tidy. The scientists reasoned that if there are more synapses than usual, perhaps there are not as many microglia in the brains of affected males.
Interestingly, the researchers found that adolescent males from the stressed mother mice had just as many microglia in the ACC as did their peers from non-stressed moms. However, smog and housing stress lead to microglia having less of the protein that stimulates their appetite for synapses, which likely explains why pruning did not take place effectively in the ACC.
By adulthood, the situation in the mouse brains had been reversed. Males from smog- and stress-exposed moms now had fewer synapses in their ACC and were more gregarious than their unexposed peers. This atypical tendency to be more outgoing rather than reserved mirrored the behavior and brain activity of mice with autism-linked genes.
The researchers demonstrated that a combination of air pollution and maternal stress exposures during pregnancy activate the maternal immune system (MIA, or maternal immune activation) of mouse dams leading to altered synaptic and microglial development, persistent changes in brain circuit function, and long-lasting alterations in social and communication behavior in male offspring. In short, the results of the study show that prenatal co-exposure to two highly prevalent environmental factors, air pollution and maternal stress, is sufficient to induce MIA (maternal immune activation) and significantly increase stress hormones in pregnant mice. The researchers say their findings illustrate the mechanism by which environmental pollutants can synergize with psychosocial stress in pregnant mothers and induce MIA, which has specific long-term effects on the development and function of male brains.
¹ Some of the studies we have published linking exposure to chemicals in air pollution to adverse health consequences:
Journal reference: Carina L. Block, Oznur Eroglu, Stephen D. Mague, Caroline J. Smith, Alexis M. Ceasrine, Chaichontat Sriworarat, Cameron Blount, Kathleen A. Beben, Karen E. Malacon, Nkemdilim Ndubuizu, Austin Talbot, Neil M. Gallagher, Young Chan Jo, Timothy Nyangacha, David E. Carlson, Kafui Dzirasa, Cagla Eroglu & Staci D. Bilbo. Prenatal environmental stressors impair postnatal microglia function and adult behavior in males, Cell Reports, Volume 40, ISSUE 5, 111161, August 02, 2022. Study | Overview DOI: https://doi.org/10.1016/j.celrep.2022.111161