Nav: Home

Placental accumulation of flame retardant chemical alters serotonin production in rats

January 22, 2018

A North Carolina State University-led research team has shown a connection between exposure to a widely used flame retardant chemical mixture and disruption of normal placental function in rats, leading to altered production of the neurotransmitter serotonin. Evidence of endocrine, inflammatory and neurotransmitter signaling pathway disruption was also identified in the placentas. These data show, for the first time, that flame retardants can have sex-specific effects on placental functions critical for brain development.

FireMaster 550 (FM550) is a flame-retardant mixture used in foam-based baby products and furniture. First identified by collaborating researchers at Duke University nearly a decade ago, it was developed to replace PBDEs, a class of fire retardants being phased out of use because of safety concerns. The interuniversity research team recently demonstrated that FM 550 is an endocrine disruptor, with developmental exposure affecting anxiety- and hyperactivity-related behaviors in rats in sex-specific ways. They also showed that three of the FM 550 components dose-dependently accumulate in placenta, with levels higher in male-associated placentas.

Heather Patisaul, professor of biology at NC State, and her graduate student, Kylie Rock, wanted to know if FM 550 could sex-specifically impact the developing brain by altering placental function. They exposed pregnant female rats to 0, 300, or 1,000 micrograms of the chemical mixture per day for 10 days during gestation. The team used a variety of tools, including metabolomics and high throughput RNA sequencing, to examine the placentas and the developing brains of the offspring to identify possible pathways impacted by the chemical mixture. The dose levels used were all below the 50 milligrams per day currently considered safe.

In rat offspring exposed to 300 or 1,000 micrograms of FM550, the researchers found dose-dependent upregulation of multiple genes related to inflammatory and endocrine processes. Some were sex-specific. For example, levels of estrogen and androgen receptors were upregulated in female-associated placentas while inflammatory markers associated with increased risk of behavioral disorders were upregulated in placentas from both sexes. Additionally, the ratio of the serotonin metabolite 5-HIAA to serotonin was reduced in female placentas and fetal forebrains compared to the control group, demonstrating disruption of neurotransmitter production in the placenta and developing brain.

"We found that exposure to FM 550 can impact multiple placental pathways critical for early brain development, which is particularly concerning given that it is commonly found in baby products and furniture," Patisaul says. "Most intriguingly, we found some evidence that placental serotonin production is altered. This is important because in early development the placenta is the sole source of serotonin for the developing forebrain."
-end-
The research appears in Endocrine Connections. Rock is first author and Patisaul is corresponding author. Collaborating efforts were led by Heather Stapleton at Duke University and Susan Sumner at UNC Chapel Hill. The work was funded by the National Institute of Environmental Health Sciences (grants R56ES022957, P30ES025128 and T32ES021432).

Note to editors: An abstract follows

"Molecular Effects of Developmental FM 550 Exposure in Wistar Rat Placenta and Fetal Forebrain"

DOI: 10.1530/EC-17-0373

Authors: Kylie D. Rock, Brian Horman, Dereje Jima, Heather Patisaul, North Carolina State University; Susan L. McRitchie, Scott Watson, Jocelin Deese-Spruill, Susan Sumner, University of North Carolina at Chapel Hill; Allison L. Phillips, Duke University

Published:Endocrine Connections

Abstract:

Firemaster® 550 (FM 550) is a flame retardant (FR) mixture that has become one of the most commonly used FRs in foam-based furniture and baby products. Human exposure to this commercial mixture, comprised of brominated and organophosphate components, is widespread. We have repeatedly shown that developmental exposure can lead to sex-specific behavioral effects in rats. Accruing evidence of endocrine disruption and potential neurotoxicity have raised concerns regarding the neurodevelopmental effects of FM 550 exposure, but the specific mechanisms of action remains unclear. Additionally, we observed significant, and in some cases sex-specific, accumulation of FM 550 in placental tissue following gestational exposure. Because the placenta is an important source of hormones and neurotransmitters for the developing brain, it may be a critical target of toxicity to consider in the context of developmental neurotoxicity. Using a mixture of targeted and exploratory approaches, the goal of the present study was to identify possible mechanisms of action in the developing forebrain and placenta. Wistar rat dams were orally exposed to FM 550 (0, 300, or 1,000 μg/day;) for 10 days during gestation and placenta and fetal forebrain tissue collected for analysis. In placenta, evidence of endocrine, inflammatory, and neurotransmitter signaling pathway disruption was identified. Notably, 5-HT turnover was reduced in placental tissue and fetal forebrains indicating that 5-HT signaling between the placenta and the embryonic brain may be disrupted. These findings demonstrate that environmental contaminants, like FM 550, have the potential to impact the developing brain by disrupting normal placental functions.

North Carolina State University

Related Serotonin Articles:

Study illuminates serotonin contributions to cocaine's allure
A new study reinforces long-held suspicions that the brain chemical serotonin, a molecule usually associated with mood, appetite and libido, makes a direct contribution to the actions of cocaine.
Serotonin improves sociability in mouse model of autism
Scientists at the RIKEN Brain Science Institute in Japan have linked early serotonin deficiency to several symptoms that occur in autism spectrum disorder (ASD).
When our world turns 'upside-down,' serotonin helps us deal with it
It has been called the 'happiness molecule' due to its antidepressant effects in drugs such as Prozac.
More serotonin, less motivation? It depends on the circumstances
Neuroscientists discovered a surprising and completely unexpected behavioral effect of serotonin in mice, which strongly suggests that this neurotransmitter is involved in a biological mechanism affecting motivation.
LSD alters perception via serotonin receptors
Researchers from UZH have discovered how the perception of meaning changes in the brain under the influence of LSD.
This is LSD attached to a brain cell serotonin receptor
For the first time, UNC School of Medicine researchers solved the structure of LSD attached to a human serotonin receptor of a brain cell, and they may have discovered why an 'acid trip' lasts so long.
Imaging technique maps serotonin activity in living brains
MIT researchers have developed an imaging technique that, for the first time, enables three-dimensional mapping of serotonin as it's reabsorbed into neurons, across multiple regions of the living brain.
Maternal inflammation boosts serotonin and impairs fetal brain development in mice
Fighting the flu during pregnancy sickens a pregnant woman, but it may also put the fetus at a slightly increased risk for neurodevelopmental disorders like autism later in life.
Serotonin reduces apnea and could be a clue to understanding sudden infant death syndrome
Serotonin, a neurotransmitter in the brain, shortens periods of apnea (temporary cessation of breathing) and promotes inspiration, according to a study published today in Experimental Physiology.
The gates of serotonin: Cracking the workings of a notorious receptor
EPFL scientists have elucidated for the first time how a notoriously elusive serotonin receptor functions with atom-level detail.

Related Serotonin Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Don't Fear Math
Why do many of us hate, even fear math? Why are we convinced we're bad at it? This hour, TED speakers explore the myths we tell ourselves and how changing our approach can unlock the beauty of math. Guests include budgeting specialist Phylecia Jones, mathematician and educator Dan Finkel, math teacher Eddie Woo, educator Masha Gershman, and radio personality and eternal math nerd Adam Spencer.
Now Playing: Science for the People

#518 With Genetic Knowledge Comes the Need for Counselling
This week we delve into genetic testing - for yourself and your future children. We speak with Jane Tiller, lawyer and genetic counsellor, about genetic tests that are available to the public, and what to do with the results of these tests. And we talk with Noam Shomron, associate professor at the Sackler School of Medicine at Tel Aviv University, about technological advancements his lab has made in the genetic testing of fetuses.