Gestational exposure to flame retardants alters brain development in rats

A new study from North Carolina State University shows that in utero exposure to the flame retardant FireMaster 550 (FM 550) or its individual brominated (BFR) or phosphate ester (OPFR) components resulted in altered brain development in newborn rats. The effects—primarily evidence of mitochondrial destruction and disturbances in choline and triglyceride levels in brain tissue—were stronger in male offspring than in female offspring.

The work adds to the evidence that both OPFR and BFR may be neurotoxic. It appears in a special issue Neuroendocrinology. Shanna Vitchey, a former doctoral student at North Carolina State, is the first author.

FM 550 is a flame retardant compound first discovered ten years ago. It was developed to replace PBDEs, a class of flame retardants that are being phased out due to safety concerns.

“Although some newer flame retardants still contain BFRs, OPFRs are a popular replacement for PBDEs because OPFRs are believed not to accumulate in the body and therefore may not be as harmful,” says Heather Patizaul, associate dean for research. in the North Carolina State College of Science and corresponding author of the study. “In particular, OPFRs were thought to have no effect on acetylcholinesterase, a key neurotransmitter. But it appears that OPFRs still affect choline signaling and are as harmful to the developing brain as, if not worse than, PBDEs.”

Patizaul and her colleagues performed transcriptomic and lipidomic studies of the prefrontal cortex of newborn rats whose mothers were exposed to FM550 or BFR or OPFR elements individually during pregnancy.

“Getting genetic information from transcriptomics is what researchers routinely do to uncover potential links between toxicity and health effects,” says Patizaul. “In this case, we also wanted to see if the lipid (or fat) composition of the brain was altered—our brains are essentially globules of fat, and lipidomics can show how exposure can affect the brain at the earliest stages of development.”

Both transcriptomic and lipidomic analyzes showed evidence of mitochondrial disruption, although the perturbations were more pronounced in OPFR-exposed offspring. Mitochondria are found in almost every cell and serve as cellular energy generators, playing a vital role in cellular respiration.

Transcriptomic analysis revealed the disorder cellular respiration genes associated with neurodegenerative diseases such as Alzheimer’s disease and ALS, while lipidomics indicates impaired choline and triglyceride levels in the brain.

Genes related to axon guidance and choline signaling were also disrupted in males exposed to OPFR. Axon guidance is the process by which neurons make the correct connections during nervous system development. Choline is a precursor to the neurotransmitter acetylcholine, which affects important aspects of neuronal function and neuronal signaling.

“With so many altered genes involved in respiration and choline, there is concern that these FRs impair basic autonomic function and cognition,” says Patizaul. “So the bottom line is that exposure to BFR and OPFR disrupts both neuronal signaling and the cells’ ability to properly produce and use energy.”

The researchers also found that male offspring suffered more than women.

“In earlier studies in rats, we found that OPFR levels were higher in placentas attached to males than to females,” says Patizaul. “So this difference in exposure may be why we see different and more severe effects in men.

“The important message here is that the perception that OPFRs are safer than other FRs is likely wrong. Both OPFR and BFR can disrupt cortical development and function. And the fact that these chemicals are found in the placenta means that they don’t break down quickly enough to do no harm.”