A new study has revealed significantly elevated levels of bisphenol A (BPA), a compound common in plastics, in pregnant mothers whose children were later diagnosed with autism. The researchers suggest that BPA interferes with fetal brain development, especially in boys, by inhibiting the enzyme aromatase, which is essential for hormone regulation in the developing brain.
Autism spectrum disorder (ASD), also known as autism, is a condition that affects neurological development, or the way the brain develops and functions.
People with ASD often have difficulty communicating and interacting socially and may exhibit repetitive behaviors, such as specific and intense movements or interests.
The condition is diagnosed clinically, so doctors and specialists identify signs and symptoms that characterize autism. It is estimated that between 1% and 2% of people in Western countries have ASD, and the incidence appears to be increasing.
Part of this increase is due to greater awareness of autism, making it easier to diagnose. However, other factors also contribute to this, including early life environment, genetics, and the interaction between genetics and environment.
Interestingly, around 80% of people diagnosed with ASD are male. This suggests that there is something specific to male brain development that may contribute to a higher risk of autism.
One hypothesis is that neurodevelopment, the process of brain formation, may differ between boys and girls in ways that increase the risk of autism for boys.
Aromatase is an enzyme in the brain that converts androgen hormones (associated with male development) into estrogen hormones (hormones typically associated with female development). During fetal brain development, especially in areas such as the amygdala (a region associated with emotions), aromatase is highly active in boys.
Studies suggest that altered aromatase levels are associated with ASD, as proposed by the “extreme male brain” theory, which suggests that autism is linked to more “masculine” features of brain development.
In autopsies of adults with ASD, males have been shown to have reduced aromatase activity compared to males without ASD. In particular, in the prefrontal cortex (an area of the brain involved in processes such as planning and decision-making), males with ASD have 38% less aromatase activity than expected.
In addition to genetic factors, the environment also plays a role. Exposure to chemicals such as bisphenol A (BPA) can interfere with aromatase function and, consequently, brain development.
Chemicals such as BPA are present in many plastics and food containers and are known to act as endocrine disruptors, which means they interfere with the production and regulation of hormones in the body.
Research has shown that exposure to BPA during pregnancy is associated with behavioral problems in children, including symptoms similar to ASD, with some of these effects being more pronounced in boys.
Studies in animals, such as mice, have also shown that exposure to BPA before birth leads to more pronounced brain and cognitive changes in males.
One hypothesis is that bisphenols, by interfering with aromatase, cause changes in brain development. This impact could occur through epigenetic changes, modifications that control gene activity without altering the DNA itself, but by influencing which genes are turned on or off.
Researchers are exploring the potential of 10-hydroxy-2-decenoic acid (10HDA), a component of royal jelly produced by bees, as an option for nutritional intervention for ASD.
Studies indicate that 10HDA helps maintain the balance of some important cellular processes in the brain and acts on elements that respond to estrogen, promoting neurogenesis (creation of new brain cells).
These effects suggest that it may be useful in counteracting the negative impacts of chemicals such as BPA on brain development, especially if more research proves these results in humans.
Researchers from the University of Melbourne investigated whether higher prenatal BPA exposure leads to an increased risk of ASD in males and explored aromatase as a potential underlying mechanism. They published their results in the renowned journal Nature Communications.
They examined the interaction between prenatal BPA, aromatase function, and sex concerning symptoms and diagnosis of human ASD in the Barwon Infant Study (BIS) birth cohort. From June 2010 to June 2013, samples were collected from 1,074 mother-infant pairs (10 sets of twins). Of these, a total of 847 children had prenatal bisphenol A measurements available.
A total of 43 children had a confirmed diagnosis of ASD by a pediatrician or psychiatrist against the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). ASD diagnoses were overrepresented in boys, with a ratio of 2.1:1 at age 9 (29 boys and 14 girls).
Mothers who had high levels of BPA during pregnancy were found to have a higher risk of developing symptoms of autism, especially boys. BPA appears to affect the functioning of aromatase, an enzyme that is crucial for regulating estrogen, a hormone that aids fetal brain development.
When aromatase is inhibited by BPA, brain development can be altered, leading to autism-like symptoms such as repetitive behaviors and social difficulties.
Experiments in mice have shown that BPA causes changes in behavior and brain structure, including changes in brain areas important for memory, sociability, and motor control.
Male mice exposed to BPA and aromatase knockout (ArKO) mice have deficits in sociability and increased grooming behavior. Sociability is the greater proportion of time spent in the stranger interaction zone compared to the empty interaction zone. In the three-chamber social interaction test (A), BPA-exposed mice spent less time investigating the stranger mouse compared to control male mice. B) ArKO male mice also spent less time with the stranger compared to WT male littermates. C) A schematic of the three-chamber sociability test. D) BPA-exposed male mice spent more time grooming themselves compared to control mice. There were no differences between BPA-exposed and control female mice.
To see if these effects could be reversed, the study also tested the use of 10HDA (a compound in royal jelly) in mice, which helped reduce the negative effects of BPA on the brain and improve social behavior in the affected mice.
The researchers suggest that reducing BPA exposure may reduce the risk of brain development problems during pregnancy. The study also points to 10HDA as a potential treatment to reduce the impacts of BPA on neurodevelopment, but more research is needed before testing in humans.
Male cortical neurons exposed to BPA and 10HDA exposure in vitro. A) Representative photomicrographs of primary cultures of mouse embryonic cortical neurons, red staining is βIII tubulin and green staining is aromatase. B) Compared to the BPA group, the vehicle and BPA + 10HDA groups have significantly longer neurites. The BPA + 10HDA group has longer neurites compared to the vehicle group, and there is no difference between the vehicle and 10HDA groups. C) Compared to the BPA group, the vehicle group and the BPA + 10HDA group have significantly higher spine densities. The BPA + 10HDA group has a higher spine density compared to the vehicle group, and there is no difference between the vehicle and 10HDA groups.
Despite the promising results, the study acknowledges some limitations. This indicates the need for further studies and, ideally, a clinical trial to confirm these effects in humans.
These findings may lead to new recommendations for BPA exposure, especially for pregnant women, and explore a potential protective approach with 10HDA.
READ MORE:
Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype.
Symeonides C, Vacy K, Thomson S, et al.
Nat Commun 15, 6367 (2024). https://doi.org/10.1038/s41467-024-48897-8
Abstract:
Male sex, early life chemical exposure, and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.
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