In utero exposure to flame retardants results in altered brain development in newborn rats

In utero exposure to flame retardants results in altered brain development in newborn rats

A new study from North Carolina State University shows that exposure to the flame retardant FireMaster® 550 (FM 550) or its individual brominated (BFR) or organophosphate ester (OPFR) components in utero resulted in altered brain development in newborn rats. The effects - particularly evidence of mitochondrial dysfunction and dysregulated choline and triglyceride levels in brain tissue - were greater in male offspring than in females. The work adds to the evidence that both OPFRs and BFRs can be neurotoxic.

FM 550 is a flame retardant blend that was first identified a decade ago. It was designed to replace PBDEs, a class of flame retardants that are being phased out for safety reasons.

While some new flame retardant blends still contain BFRs, the OPFRs are a popular replacement for PBDEs because it is believed that OPFRs do not accumulate in the body and therefore cannot be as harmful. In particular, it was hypothesized that OPFRs would not affect acetylcholinesterase – an important neurotransmitter. But it looks like OPFRs still affect choline signaling and are just as bad, if not worse, for the developing brain than PBDEs.”

Heather Patisaul, associate dean for research at NC State College of Sciences and corresponding author of the study

Patisaul and her colleagues conducted transcriptomic and lipidomic studies on the prefrontal cortices of newborn rats whose mothers were exposed to FM550 or individually to BFR or OPFR elements during pregnancy.

“Obtaining genetic information from transcriptomics is what researchers commonly do to uncover potential links between toxicity and health effects,” says Patisaul. "In this case, we also wanted to see whether the lipid or fat composition of the brain was altered - our brains are essentially balls of fat, and lipidomics can reveal how exposure can affect the brain in its earliest stages of development."

Both transcriptomic and lipidomic analyzes showed evidence of mitochondrial disruption, although the disruption was more pronounced in the offspring exposed to OPFRs. Mitochondria are found in almost every cell and serve as cellular energy generators, playing an important role in cellular respiration.

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Transcriptome analysis revealed disruption of cellular respiration genes associated with neurodegenerative diseases such as Alzheimer's and ALS, while lipidomics indicated disrupted choline and triglyceride levels in the brain.

In men exposed to OPFRs, genes associated with axon guidance and choline signaling were also dysregulated. Axon guidance is the process by which neurons make the proper connections during neural development. Choline is a precursor to the neurotransmitter acetylcholine, which influences critical aspects of neuronal function and neuronal signaling.

“Because so many altered genes are involved in respiration and choline, there is concern that these FRs affect basic autonomic functions and cognition,” says Patisaul. “So the bottom line is that exposure to BFRs and OPFRs disrupts both neuronal signaling and the ability of cells to properly produce and use energy.”

The researchers also found that male offspring were more affected than females.

“In previous rat studies, we found that OPFR levels are higher in placentas attached to males than females,” says Patisaul. “So this difference in exposure could be why we see different and more severe effects in men.

"The important message here is that the assumption that OPFRs are safer than other FRs is probably wrong. Both OPFRs and BFRs can disrupt cortical development and function. And the fact that these chemicals are detectable in the placenta means that they do not break down quickly enough to not cause harm."

The work appears in a special issue of Neuroendocrinology and was supported by the National Institute of Environmental Health Sciences (NIEHS) and the Environmental Protection Agency. The first author is Shannah Witchey, a former postdoctoral researcher at NC State. biggest concern.

Source:

North Carolina State University

Reference:

Witchey, SK, et al. (2022) The effects of gestational FireMaster 550 (FM 550) exposure on the neonatal cortex are sex-specific and largely attributable to organophosphate esters. Neuroendocrinology. doi.org/10.1159/000526959.

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