Mouse study finds BPA exposure has transgenerational effects on gene linked to autism

Summary: Exposure to BPA appears to have a transgenerational effect on autism risk. Mice whose great grandmothers were exposed to BPA during pregnancy exhibited social behavioral deficits associated with ASD.

Source: The Endocrine Society

Transgenerational bisphenol A (BPA) exposure may contribute to autism, according to a mouse study published in the Endocrine Society’s journal Endocrinology.

Endocrine disrupting chemicals (EDCs) are chemicals or mixtures of chemicals that interfere with the way the body’s hormones work. BPA is a common EDC used in plastics and food storage material, and it is already present in most humans’ urine or blood. Animal studies have linked BPA to anxiety, aggression, and poor learning and social interactions. Studies of human populations report associations between BPA and neurobehavioral issues like attention deficit hyperactivity disorder and autism.

“Exposure of mouse fetuses to BPA disrupts formation of nerve cell connections in the brain, and this is a transgenerational effect,” said the study’s senior author, Emilie F. Rissman, Ph.D., of University of Virginia School of Medicine in Charlottesville, Va. and North Carolina State University in Raleigh, N.C. “To put this in human terms, if your great grandmother was exposed to BPA during her pregnancy and none of your other relatives ever came into contact with BPA, your brain would still show these effects.”

This shows plastic water bottles
In this mouse study, researchers tested mice descended from those exposed to BPA for social recognition and found that they showed a social behavioral deficient like autistic behavior. The image is credited to NIH/NIEHS.

In this mouse study, researchers tested mice descended from those exposed to BPA for social recognition and found that they showed a social behavioral deficient like autistic behavior. Mice whose great grandmothers were exposed to BPA during pregnancy were more active and took longer to habituate to strangers than other mice. More strikingly, they didn’t explore the new mice that were introduced to the group. Mice are very social and curious, so this is an exciting finding.

“Even if we ban all BPA right now, that will not change these long-term effects on the brain,” Rissman said.

Other authors of the study include: Jennifer T. Wolstenholme of the University of Virginia School of Medicine in Charlottesville, Va., and Virginia Commonwealth University in Richmond, Va.; Zuzana Drobná and Joshua W. Irvin of North Carolina State University; Anne D. Henriksen of James Madison University in Harrisonburg, Va.; Jessica A. Goldsby of the University of Virginia School of Medicine; Rachel Stevenson of Virginia Commonwealth University; and Jodi A. Flaws of the University of Illinois in Urbana, Ill.

Funding: The study received funding support from the National Institutes of Health and the Environmental Protection Agency.

About this neuroscience research article

Source:
The Endocrine Society
Media Contacts:
Jenni Glenn Gingery – The Endocrine Society
Image Source:
The image is credited to NIH/NIEHS.

Original Research: Open access
“Transgenerational Bisphenol A causes deficits in social recognition and alters post-synaptic density genes in mice”. Jennifer T Wolstenholme, Zuzana Drobná, Anne D Henriksen, Jessica A Goldsby, Rachel Stevenson, Joshua W Irvin, Jodi A Flaws, Emilie F Rissman.
Endocrinology. doi:10.1210/en.2019-00196

Abstract

Transgenerational Bisphenol A causes deficits in social recognition and alters post-synaptic density genes in mice

Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical (EDC). Developmental exposure produces changes in behavior and gene expression in brain. Here we examined social recognition behaviors in mice, three generations (F3) after exposure to gestational BPA. Second generation mice were bred in one of four mating combinations to reveal whether characteristics in F3 were acquired via maternal or paternal exposures. After repeated habituation to the same mouse, offspring of dams from the BPA-lineage failed to display increased investigation of a novel mouse. Genes involved in excitatory post-synaptic densities (PSD) were examined in F3 brains using qPCR. Differential expression of genes important for function and stability of PSDs were assessed at three developmental ages. Several related PSD genes ― SH3 and multiple ankyrin repeat domains 1 (Shank1), Homer scaffolding protein 1c (Homer1c), DLG associated protein 1 (Gkap), and discs large MAGUK scaffold protein 4 (PSD95) ― were differentially expressed in control- versus BPA-lineage brains. Using a second strain of F3 inbred mice exposed to BPA, we noted the same differences in Shank1 and PSD95 expression found in C57BL/6J mice. In sum, transgenerational BPA exposure disrupted social interactions in mice and dysregulated normal expression of PSD genes during neural development. The fact that the same genetic effects were found in two different mouse strains and in several brain regions, increased potential for translation. The genetic and functional relationship between PSD and abnormal neurobehavioral disorders is well established and our data suggest that BPA may contribute, in a transgenerational manner, to neurodevelopmental diseases.

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