New research is shedding light on the relationship between prenatal exposure to environmental chemicals and the development of neurodevelopmental disorders such as autism spectrum disorder (ASD). In a recent CHE webinar, Dr. Anne-Louise Ponsonby presented findings from a study examining how prenatal BPA exposure may disrupt fetal brain development in ways that increase the incidence of ASD. This study is particularly important because it helps to shed light on a possible mechanism of autism development.
Bisphenol A (BPA), which is used in a variety of products including certain plastics, is known to be an endocrine-disrupting compound. Numerous studies have shown a relationship between bisphenol exposures and neurodevelopmental disorders. For example, a review in 2021 found that prenatal exposure to bisphenols and phthalates may contribute to adverse neurodevelopmental outcomes in children.
Despite this, regulation of these chemicals has been slow. Stronger causal evidence could help bolster efforts to regulate these chemicals and protect human health.
Testing a hypothesis
Up to 80% of individuals diagnosed with ASD are male, suggesting that sex-specific effects on neurodevelopment underlie this condition. Some evidence suggests that BPA may disrupt hormonal pathways critical for early brain development. A key player in this disruption appears to be the brain aromatase enzyme, which regulates the conversion of androgens to estrogens and influences neurodevelopment. During fetal development in males, aromatase expression within the brain’s amygdala is higher than in females.
Researchers set out to test the hypothesis that BPA exposure in utero could be linked to autism through brain aromatase disruption. Because aromatase is particularly important in male brain development, under this hypothesis, males would be expected to be more affected by prenatal BPA exposure.
Dr. Ponsonby explained that in the second trimester of male fetal development, aromatase plays a key role in generating neuroestrogens from testosterone. This process is crucial in the development of the social functions in the brain.
The study included analyses of BPA exposures and their effects in two human cohorts, the effects of BPA exposure on humans and mice, and the effects of BPA exposure at the cellular level, in vivo and in vitro.
Key findings:
- In mice, BPA reduced aromatase expression in the medial amygdala (which is involved in social behavior).
- Both male BPA-exposed mice and aromatase knockout (ArKO) mice demonstrated ASD-like behavioral and brain changes at structural and functional levels. (ArKO mice are mice that lack the gene to encode for aromatase).
- Boys with low aromatase activity have greater odds of ASD diagnosis at age 9 and ASD symptoms at age 2 when exposed to high levels of BPA in utero.
- Prenatal BPA exposure predicted higher methylation across a genetic region that is linked to aromatase gene activity. Laboratory studies found that this methylation mediates the association between prenatal BPA exposure and changes in brain-derived neurotrophic factor (BDNF) methylation, an essential component of neuroplasticity and synaptic function.
As predicted by the hypothesis, males were more likely to be affected by BPA exposure than females. However, not all males showed the same association. Instead, the association was found in males who were identified as genetically more vulnerable to the impacts of BPA. As with other multifactorial conditions, the interaction between genetic characteristics and environmental exposures can contribute to the development of autism.
The study findings support an underlying causal relationship between prenatal BPA exposure and ASD. This study also points to potential therapies for reversing BPA’s effects on aromatase.
Implications
BPA is the most studied bisphenol, but it is not the only concern. Substitute bisphenols, such as BPS and BPF, have similar chemical structures and therefore behave similarly at the molecular level. Research has been showing for years that these BPA-substitute bisphenols can have similar endocrine-disrupting effects.
Phthalates, which are also commonly used in plastics, have also been shown to have similar effects on aromatase. With bisphenols and phthalates used in so many consumer products, they are largely unavoidable. This is why we need stronger regulations that can protect everyone’s health.
In her presentation, Dr. Ponsonby expressed hope that the Global Plastics Treaty negotiations would take into account the human health impacts of early-life exposure to chemicals in plastics, and move to phase out these substances.
For more on prenatal BPA exposure and ASD, see our webinar Male autism spectrum disorder & prenatal BPA exposure. And for another helpful discussion of the significance of this study, see Bruce Lanphear's blog post Plastic Chemicals—A Hidden Link to Autism?
This organizational blog was produced by CHE's Science Writer, Matt Lilley.