Sex-specific effects on elements of the social brain neural network in Wistar rats from perinatal exposure to FireMaster 550 or its components
Abstract
Developmental exposure to chemical flame retardants (FRs) has been linked to a variety of neurodevelopmental disorders and abnormal socioemotional behaviors in human and laboratory animal studies. We have previously shown in Wistar rats that gestational and lactational exposure to the FR mixture Firemaster 550 (FM 550) or its brominated or organophosphate ester (OPFR) components (at 2000 µg, 1000 µg, and 1000 µg oral to the dam respectively (absolute and not by bodyweight)) results in increased anxiety-like behaviors in females and decreased sociality in both sexes. Using their siblings, this study characterized sex and chemical specific targets of disruption in brain regions underlying each behavioral phenotype. Offspring were exposed across gestation and lactation then prepared for either immunohistochemistry or autoradiography at postnatal day 90 to quantify expression of serotonin, estrogen receptor α (ERα), and oxytocin receptor (OTR) in multiple brain regions. No effect of exposure was found in males for any biological target. In females, serotonin innervation was increased in the medial amygdala of FM 550 exposed animals while ERα expression in the bed nucleus of the stria terminalis (BNST) was reduced by FM 550 and OPFR. Evidence of disrupted OTR was observed in males, particularly the BNST but considered an exploratory finding given the small sample size. These results begin to shed light on the mechanisms by which developmental FR exposure alters socioemotional beha…
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Perinatal FireMaster 550 exposure causes sex- and chemical-specific disruption of social-brain targets involving oxytocin receptor- and serotonin-related signaling.
“More recent work also indicates sex- and chemical-specific disruption of social-brain targets involving oxytocin receptor- and serotonin-related signaling after perinatal FireMaster 550 exposure (Krentzel et al., 2021; 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 Schkoda et al., 2024
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 Schkoda et al., 2024
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 Schkoda et al., 2024
Recent work in Wistar rats indicates sex- and chemical-specific disruption of oxytocin receptor- and serotonin-related elements of the social-brain network after perinatal FM 550 or component exposure.
“Recent work in Wistar rats further indicates sex- and chemical-specific disruption of oxytocin receptor- and serotonin-related elements of the social-brain network after perinatal FM 550 or component exposure, providing a plausible circuit-level substrate for altered socioemotional behavior (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 Schkoda et al., 2024
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 Schkoda et al., 2024
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 Schkoda et al., 2024
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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
“More recent work also indicates sex-and chem-ical-specific disruption of social-brain targets involving oxytocin receptor-and serotonin-related signaling after perinatal FireMaster 550 exposure (Krentzel et al., 2021; Schkoda et al., 2024).”
- Authors
- Schkoda, S., Horman, B., Witchey, S., St. Armour, G., Nelson, M., Gaeta, E., Scott, M., & Patisaul, H. B.
- Affiliations
- North Carolina State University (US)
- Corresponding author
- Patisaul, Heather B.
- Venue
- NeuroToxicology
- Publisher
- Elsevier BV
- Published
- 2024-12
- Volume
- 105
- Pages
- 111-120
- ISSN
- 0161-813X (ISSN-L)
- OpenAlex
- W4402282408
- Cited by
- 2
- References
- 10
- Citations by year
- 2026: 1 · 2025: 1
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroToxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (ES033825)
- National Institute of Environmental Health Sciences
- U.S. Department of Defense (AR160055)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Keywords
- brominated flame retardants, organophosphate flame retardants, developmental neurotoxicity, sex differences, social brain network, serotonin innervation, estrogen receptor alpha, oxytocin receptor, medial amygdala, bed nucleus of the stria terminalis, anxiety-like behavior, sociality, neurodevelopmental disorders, social-emotional behavior
- MeSH terms
- Animals, Brain, Female, Flame Retardants, Male, Nerve Net, Pregnancy, Prenatal Exposure Delayed Effects, Serotonin, Sex Characteristics, Social Behavior, Rats, Wistar, Receptors, Oxytocin, Estrogen Receptor alpha, Rats
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