Gestational exposure to FireMaster® 550 (FM 550) disrupts the placenta-brain axis in a socially monogamous rodent species, the prairie vole (Microtus ochrogaster)
Open accessAbstract
Gestational flame retardant (FR) exposure has been linked to heightened risk of neurodevelopmental disorders, but the mechanisms remain largely unknown. Historically, toxicologists have relied on traditional, inbred rodent models, yet those do not always best model human vulnerability or biological systems, especially social systems. Here we used prairie voles (Microtus ochrogaster), a monogamous and bi-parental rodent, leveraged for decades to decipher the underpinnings of social behaviors, to examine the impact of fetal FR exposure on gene targets in the mid-gestational placenta and fetal brain. We previously established gestational exposure to the commercial mixture Firemaster 550 (FM 550) impairs sociality, particularly in males. FM 550 exposure disrupted placental monoamine production, particularly serotonin, and genes required for axon guidance and cellular respiration in the fetal brains. Effects were dose and sex specific. These data provide insights on the mechanisms by which FRs impair neurodevelopment and later in life social behaviors.
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Developmental organophosphate ester exposure produced sex-specific hippocampal transcriptomic changes enriched for cation-transport pathways, including voltage-gated potassium and calcium channel genes and subunits, and involving mitochondrial regulation.
“developmental organophosphate ester exposure produced sex-specific hippocampal transcriptomic changes enriched for cation-transport pathways, including voltage-gated potassium and calcium channel genes and subunits”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
Prenatal exposure to a mixture of OPFRs altered placental gene programs linked to oxidative-stress defense, including downregulation of Sod2.
“Prenatal exposure to a mixture of OPFRs altered placental gene programs linked to oxidative-stress defense, including downregulation of Sod2, while developmental organophosphate ester exposure in brain produced transcriptomic signatures enriched for mitochondrial transcriptional regulation.”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
Gestational FireMaster 550 exposure disrupted placental monoamine production, particularly serotonin, and altered fetal-brain genes required for cellular respiration.
“In a complementary prairie vole model, gestational FireMaster 550 exposure disrupted placental monoamine production, particularly serotonin, and altered fetal-brain genes required for cellular respiration.”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
FRs can compromise both redox buffering and mitochondrial/metabolic support during synaptic development.
“These observations indicate that FRs can compromise both redox buffering and mitochondrial/metabolic support during synaptic development (Marinello et al., 2023; Newell et al., 2023a; Rock et al., 2020).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
Perinatal FM 550 exposure altered social-brain targets in a sex- and chemical-specific manner, including oxytocin receptor- and serotonin-related elements in regions such as the amygdala and BNST.
“while perinatal FM 550 exposure altered social-brain targets in a sex- and chemical-specific manner, including oxytocin receptor- and serotonin-related elements in regions such as the amygdala and BNST.”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
These data support the interpretation that FRs can leave persistent transcriptional imprints on neurodevelopmental pathways, even when DNA methylation or histone marks were not directly measured.
“These data support the interpretation that FRs can leave persistent transcriptional imprints on neurodevelopmental pathways, even when DNA methylation or histone marks were not directly measured (Marinello et al., 2023; Newell et al., 2023a).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
Developmental FM 550 exposure changed intrinsic membrane properties of nucleus accumbens core medium spiny neurons, showing reduced input resistance in both sexes.
“In addition, developmental FM 550 exposure changed intrinsic membrane properties of nucleus accumbens core medium spiny neurons, showing reduced input resistance in both sexes.”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
Gestational FireMaster 550 exposure disrupted the placenta-brain axis, with dose- and sex-specific changes in placental monoamine production and fetal-brain axon-guidance programs.
“Gestational FireMaster 550 exposure disrupted the placenta–brain axis, with dose- and sex-specific changes in placental monoamine production and fetal-brain axon-guidance programs, while perinatal FM 550 exposure altered social-brain targets in a sex- and chemical-specific manner, including oxytocin receptor- and serotonin-related elements in regions such as the amygdala and BNST.”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
FRs destabilize circuit-level excitability and the developmental organization of socially relevant neural networks.
“Together, these findings indicate that FRs destabilize circuit-level excitability and the developmental organization of socially relevant neural networks (Krentzel et al., 2021; Marinello et al., 2023; Schkoda et al., 2024).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
Recent developmental studies indicate durable gene-regulatory reprogramming by FRs.
“Direct evidence that FRs induce classical epigenetic remodeling remains less developed than for bisphenols or phthalates, but recent developmental studies indicate durable gene-regulatory reprogramming.”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Marinello et al., 2023
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Jocsak, G., Kiss, D. S., Alymbaeva, D., Diebald, A., Zsarnovszky, A., Heinzlmann, A., & Bartha, T. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1821381 · Cited by 1 · see citing works
“These data support the interpretation that FRs can leave persistent transcriptional imprints on neuro-developmental pathways, even when DNA methylation or histone marks were not directly measured (Marinello et al., 2023; Newell et al., 2023a).”
- Authors
- Marinello, W. P., Gillera, S. E. A., Han, Y., Richardson, J. R., St Armour, G., Horman, B. M., & Patisaul, H. B.
- Affiliations
- North Carolina State University (US)
- Florida International University (US)
- Corresponding author
- Patisaul, Heather B.
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2023-10
- Volume
- 576
- Pages
- 112041
- ISSN
- 0303-7207 (ISSN-L)
- PMC
- PMC10795011
- OpenAlex
- W4385652304
- Cited by
- 6
- References
- 9
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 312 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular and Cellular Endocrinology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- National Institute of Environmental Health Sciences (P30ES25128)
- CDMRP (AR160055)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- flame retardants, prenatal exposure, Microtus ochrogaster, neurodevelopmental disorders, social behavior, serotonin, axon guidance, cellular respiration, sex differences, dose-dependent effects, fetal brain
- MeSH terms
- Animals, Brain, Arvicolinae, Female, Humans, Male, Organophosphates, Placenta, Polybrominated Biphenyls, Pregnancy, Grassland
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