Nature Communications (Aug 2024)
Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype
- Christos Symeonides,
- Kristina Vacy,
- Sarah Thomson,
- Sam Tanner,
- Hui Kheng Chua,
- Shilpi Dixit,
- Toby Mansell,
- Martin O’Hely,
- Boris Novakovic,
- Julie B. Herbstman,
- Shuang Wang,
- Jia Guo,
- Jessalynn Chia,
- Nhi Thao Tran,
- Sang Eun Hwang,
- Kara Britt,
- Feng Chen,
- Tae Hwan Kim,
- Christopher A. Reid,
- Anthony El-Bitar,
- Gabriel B. Bernasochi,
- Lea M. Durham Delbridge,
- Vincent R. Harley,
- Yann W. Yap,
- Deborah Dewey,
- Chloe J. Love,
- David Burgner,
- Mimi L. K. Tang,
- Peter D. Sly,
- Richard Saffery,
- Jochen F. Mueller,
- Nicole Rinehart,
- Bruce Tonge,
- Peter Vuillermin,
- the BIS Investigator Group,
- Anne-Louise Ponsonby,
- Wah Chin Boon
Affiliations
- Christos Symeonides
- Minderoo Foundation
- Kristina Vacy
- The Florey Institute of Neuroscience and Mental Health
- Sarah Thomson
- The Florey Institute of Neuroscience and Mental Health
- Sam Tanner
- The Florey Institute of Neuroscience and Mental Health
- Hui Kheng Chua
- The Florey Institute of Neuroscience and Mental Health
- Shilpi Dixit
- The Florey Institute of Neuroscience and Mental Health
- Toby Mansell
- Murdoch Children’s Research Institute
- Martin O’Hely
- Murdoch Children’s Research Institute
- Boris Novakovic
- Murdoch Children’s Research Institute
- Julie B. Herbstman
- Columbia Center for Children’s Environmental Health, Columbia University
- Shuang Wang
- Columbia Center for Children’s Environmental Health, Columbia University
- Jia Guo
- Columbia Center for Children’s Environmental Health, Columbia University
- Jessalynn Chia
- The Florey Institute of Neuroscience and Mental Health
- Nhi Thao Tran
- The Florey Institute of Neuroscience and Mental Health
- Sang Eun Hwang
- The Florey Institute of Neuroscience and Mental Health
- Kara Britt
- Department of Anatomy and Developmental Biology, Monash University
- Feng Chen
- The Florey Institute of Neuroscience and Mental Health
- Tae Hwan Kim
- The Florey Institute of Neuroscience and Mental Health
- Christopher A. Reid
- The Florey Institute of Neuroscience and Mental Health
- Anthony El-Bitar
- The Florey Institute of Neuroscience and Mental Health
- Gabriel B. Bernasochi
- The Florey Institute of Neuroscience and Mental Health
- Lea M. Durham Delbridge
- Faculty Medicine, Dentistry & Health Sciences, University of Melbourne
- Vincent R. Harley
- Department of Anatomy and Developmental Biology, Monash University
- Yann W. Yap
- The Hudson Institute of Medical Research
- Deborah Dewey
- Departments of Paediatrics and Community Health Sciences, The University of Calgary
- Chloe J. Love
- School of Medicine, Deakin University
- David Burgner
- Murdoch Children’s Research Institute
- Mimi L. K. Tang
- Murdoch Children’s Research Institute
- Peter D. Sly
- School of Medicine, Deakin University
- Richard Saffery
- Murdoch Children’s Research Institute
- Jochen F. Mueller
- Queensland Alliance for Environmental Health Sciences, The University of Queensland
- Nicole Rinehart
- Monash Krongold Clinic, Faculty of Education, Monash University
- Bruce Tonge
- Centre for Developmental Psychiatry and Psychology, Monash University
- Peter Vuillermin
- Murdoch Children’s Research Institute
- the BIS Investigator Group
- Anne-Louise Ponsonby
- Murdoch Children’s Research Institute
- Wah Chin Boon
- The Florey Institute of Neuroscience and Mental Health
- DOI
- https://doi.org/10.1038/s41467-024-48897-8
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 22
Abstract
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 and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.
