Neuroscience and psychology
Prenatal exposure to endocrine disruptors increases the risk of autism
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Ainhoa Pérez
Alumni
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MPH, MSc.
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Autism spectrum disorder is a neurodevelopmental condition that manifests later in life with symptoms such as difficulties in social interaction and a tendency toward repetitive behaviors. It is significantly more common in males, accounting for around 70-80% of cases diagnosed in studies with the best methodology for minimizing diagnostic bias, suggesting a vulnerability related to male-specific neurobiological development. A key factor contributing to this difference is the activity of aromatase, an enzyme responsible for converting androgens into estrogens in brain regions involved in emotional and social processing. Prenatal exposure to endocrine disruptors such as bisphenol A, one of several bisphenols present in plastics, has been identified as a factor that alters hormonal signaling during fetal development, potentially affecting aromatase function.
A recent study (Chin et al., 2024) evaluated the relationship between prenatal exposure to bisphenol A and the onset of autism spectrum disorder symptoms in children. More than 1,000 participants were recruited from the Barwon Infant Study cohort, and BPA levels were measured in maternal urine samples during pregnancy. Autism spectrum symptoms were assessed at different points in the child's life using validated scales. In addition, a genetic score based on polymorphisms associated with aromatase activity was developed. The Columbia Centre for Children's Health Study-Mothers and Newborns cohort was used to replicate the findings.
The results showed that high levels of prenatal bisphenol A correlated with a significant increase in autism spectrum symptoms in male children with low genetic aromatase activity. These children had higher scores on the early autism spectrum problems scale and a higher risk of clinical diagnosis of autism spectrum disorder at age 9. In males, prenatal bisphenol was associated with increased methylation of the CYP19A1 gene promoter, which regulates aromatase expression in the brain, which was confirmed by umbilical cord blood analysis and replicated in a second cohort. In addition, hypermethylation of the BDNF gene, crucial for neurogenesis and learning, was observed, suggesting a molecular link between prenatal exposure to bisphenol A and epigenetic alterations that impact neuronal development.
The study also included experiments in animal models and human cells. In cell cultures, exposure to bisphenol A reduced aromatase levels by half. In animal models, mice exposed to bisphenol A during gestation and aromatase knockout (ArKO) mice showed social deficits and repetitive behaviors similar to the symptoms of autism spectrum disorder in humans. These mice also had alterations in the amygdala and sensorimotor cortex, including a decrease in the number of neurons and dendrite density. The social deficits were reversed by postnatal administration of estradiol, confirming the relationship between aromatase dysfunction and these behaviors. Additionally, administration of 10-hydroxy-2-decenoic acid, a fatty acid with estrogenic properties present in royal jelly, restored social behaviors and altered neuronal structure, reversing the effects of bisphenol A on dendrites and neuronal spines.
In conclusion, the findings of this study indicate that prenatal exposure to bisphenol A interferes with aromatase function, affecting brain development in males and contributing to the onset of autism spectrum symptoms. These effects appear to be mediated by reduced aromatase activity and epigenetic alterations in key genes for neurogenesis, such as CYP19A1 and BDNF, which negatively affect neuronal development. The main limitations of the study include the single measurement of bisphenol A during pregnancy and the lack of long-term follow-up in humans. Therefore, further research and clinical studies are needed to confirm these results.
A recent study (Chin et al., 2024) evaluated the relationship between prenatal exposure to bisphenol A and the onset of autism spectrum disorder symptoms in children. More than 1,000 participants were recruited from the Barwon Infant Study cohort, and BPA levels were measured in maternal urine samples during pregnancy. Autism spectrum symptoms were assessed at different points in the child's life using validated scales. In addition, a genetic score based on polymorphisms associated with aromatase activity was developed. The Columbia Centre for Children's Health Study-Mothers and Newborns cohort was used to replicate the findings.
The results showed that high levels of prenatal bisphenol A correlated with a significant increase in autism spectrum symptoms in male children with low genetic aromatase activity. These children had higher scores on the early autism spectrum problems scale and a higher risk of clinical diagnosis of autism spectrum disorder at age 9. In males, prenatal bisphenol was associated with increased methylation of the CYP19A1 gene promoter, which regulates aromatase expression in the brain, which was confirmed by umbilical cord blood analysis and replicated in a second cohort. In addition, hypermethylation of the BDNF gene, crucial for neurogenesis and learning, was observed, suggesting a molecular link between prenatal exposure to bisphenol A and epigenetic alterations that impact neuronal development.
The study also included experiments in animal models and human cells. In cell cultures, exposure to bisphenol A reduced aromatase levels by half. In animal models, mice exposed to bisphenol A during gestation and aromatase knockout (ArKO) mice showed social deficits and repetitive behaviors similar to the symptoms of autism spectrum disorder in humans. These mice also had alterations in the amygdala and sensorimotor cortex, including a decrease in the number of neurons and dendrite density. The social deficits were reversed by postnatal administration of estradiol, confirming the relationship between aromatase dysfunction and these behaviors. Additionally, administration of 10-hydroxy-2-decenoic acid, a fatty acid with estrogenic properties present in royal jelly, restored social behaviors and altered neuronal structure, reversing the effects of bisphenol A on dendrites and neuronal spines.
In conclusion, the findings of this study indicate that prenatal exposure to bisphenol A interferes with aromatase function, affecting brain development in males and contributing to the onset of autism spectrum symptoms. These effects appear to be mediated by reduced aromatase activity and epigenetic alterations in key genes for neurogenesis, such as CYP19A1 and BDNF, which negatively affect neuronal development. The main limitations of the study include the single measurement of bisphenol A during pregnancy and the lack of long-term follow-up in humans. Therefore, further research and clinical studies are needed to confirm these results.
#Pregnancy #pediatrics #autism #maternalandchildhealth #disruptors #xenobiotics #microplastics
References:
Symeonides, C et al, 2024. Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype. Nat Commun 15, 6367 (2024). https://doi.org/10.1038/s41467-024-48897-8
* The news published on studies do not represent an official position of ICNS, nor a clinical recommendation.
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