Exposure to flame retardants during pregnancy alters brain development in rats

A new study from North Carolina State University showed that exposure to the flame retardant FireMaster?550 (FM 550) or its brominated (BFR) or organophosphate (OPFR) components in utero alters brain development
in newborn rats.
This effect — most evident evidence of mitochondrial destruction and dysregulated choline and triglyceride levels in brain tissue — was greater
in male offspring than in female offspring.
This work provides further evidence that both OPFRs and BFRs can be neurotoxic.

FM550 is a flame retardant mixture that was first discovered
a decade ago.
It is used to replace PBDEs, a class of flame retardants
that have been phased out due to safety concerns.

"While some new flame retardant mixtures still contain brominated flame retardants, OPFRs are a popular alternative to PBDEs because OPFRs are not thought to accumulate in the body and are therefore less harmful," said
Heather Patisaul, associate dean of research at the North Carolina Institute of Technology and corresponding author of the study.
Specifically, OPFRs are thought to not affect acetylcholinesterase
, a key neurotransmitter.
But it seems that OPFRs still affect choline signaling and are as bad
, if not worse, than PBDEs for the developing brain.
”

Pattisol and her colleagues conducted transcriptomic and lipidomic studies
of the prefrontal cortex of female mice exposed to FM550, BFR, or OPFR elements during pregnancy.

"Obtaining genetic information from transcriptomics is how researchers often tease out potential links between toxicity and health effects," Pattisol said
.
"In this case, we also wanted to see if the lipid or fat composition of the brain was altered – our brains are essentially fat globules, and lipidomics could reveal the effects
of exposure to early developmental stages on the brain.
"

Both transcriptome and lipidome analysis showed evidence of mitochondrial disruption, although this disruption was more pronounced
in offspring exposed to OPFRs.
Mitochondria are found in almost every cell and are cellular energy generators that play a vital role
in cellular respiration.

Transcriptomic analysis found disruption of cellular respiration genes associated with neurodegenerative diseases such as Alzheimer's and amyotrophic lateral sclerosis, while lipidomic analysis noted disruption of choline and triglyceride levels in the brain
.

In males exposed to OPFRs, dysregulation
of genes associated with axonal guidance and choline signaling also occurred.
Axon guidance is the process by which
neurons make proper connections during neurodevelopment.
Choline is a precursor to the neurotransmitter acetylcholine, which affects key aspects of
neuronal function and neuronal signaling.

"With so many altered genes associated with respiration and choline, there is concern that these FRs impair basic autonomic function and cognition
," Patisol said.
"So, the bottom line is that exposure to BFRs and OPFRs disrupts neuronal signaling and the ability of cells to
properly produce and utilize energy.
"

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

"In earlier rat studies, we found that the levels of OPFR in the placenta were higher in males than in females," Pattisol said
.
"So, the difference in exposure may be the reason why
we see different and more heavily impacted in men.
"

"The important message here is that the assumption that opfr is safer than other FRs is likely to be wrong
.
Both OPFRs and BFRs interfere with cortical development and function
.
In fact, these chemicals can be detected in the placenta, meaning they don't break down fast enough to cause damage
.
”

The study was published in a special issue of Neuroendocrinology and supported by the National Institute of Environmental Health Sciences (NIEHS) and the U.
S.
Environmental Protection Agency
.
Conflicts of
interest.