@article{marinello_gillera_han_richardson_st armour_horman_patisaul_2023, title={Gestational exposure to FireMaster® 550 (FM 550) disrupts the placenta-brain axis in a socially monogamous rodent species, the prairie vole (<i>Microtus ochrogaster</i>)}, volume={576}, ISSN={["1872-8057"]}, DOI={10.1016/j.mce.2023.112041}, abstractNote={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.}, journal={MOLECULAR AND CELLULAR ENDOCRINOLOGY}, author={Marinello, William P. and Gillera, Sagi Enicole A. and Han, Yoonhee and Richardson, Jason R. and St Armour, Genevieve and Horman, Brian M. and Patisaul, Heather B.}, year={2023}, month={Oct} }
 @article{marinello_gillera_fanning_malinsky_rhodes_horman_patisaul_2022, title={Effects of developmental exposure to FireMaster (R) 550 (FM 550) on microglia density, reactivity and morphology in a prosocial animal model}, volume={91}, ISSN={["1872-9711"]}, url={http://dx.doi.org/10.1016/j.neuro.2022.04.015}, DOI={10.1016/j.neuro.2022.04.015}, abstractNote={Microglia are known to shape brain sex differences critical for social and reproductive behaviors. Chemical exposures can disrupt brain sexual differentiation but there is limited data regarding how they may impact microglia distribution and function. We focused on the prevalent flame retardant mixture Firemaster 550 (FM 550) which is used in foam-based furniture and infant products including strollers and nursing pillows because it disrupts sexually dimorphic behaviors. We hypothesized early life FM 550 exposure would disrupt microglial distribution and reactivity in brain regions known to be highly sexually dimorphic or associated with social disorders in humans. We used prairie voles (Microtus ochrogaster) because they display spontaneous prosocial behaviors not seen in rats or mice and are thus a powerful model for studying chemical exposure-related impacts on social behaviors and their underlying neural systems. We have previously demonstrated that perinatal FM 550 exposure sex-specifically impacts socioemotional behaviors in prairie voles. We first established that, unlike in rats, the postnatal colonization of the prairie vole brain is not sexually dimorphic. Vole dams were then exposed to FM 550 (0, 500, 1000, 2000 µg/day) via subcutaneous injections through gestation, and pups were directly exposed beginning the day after birth until weaning. Adult offspring's brains were assessed for number and type (ramified, intermediate, ameboid) of microglia in the medial prefrontal cortex (mPFC), cerebellum (lobules VI-VII) and amygdala. Effects were sex- and dose-specific in the regions of interests. Overall, FM 550 exposure resulted in reduced numbers of microglia in most regions examined, with the 1000 µg FM 550 exposed males particularly affected. To further quantify differences in microglia morphology in the 1000 µg FM 550 group, Sholl and skeleton analysis were carried out on individual microglia. Microglia from control females had a more ramified phenotype compared to control males while 1000 µg FM 550-exposed males had decreased branching and ramification compared to same-sex controls. Future studies will examine the impact on the exposure to FM 550 on microglia during development given the critical role of these cells in shaping neural circuits.}, journal={NEUROTOXICOLOGY}, publisher={Elsevier BV}, author={Marinello, William P. and Gillera, Sagi Enicole A. and Fanning, Marley J. and Malinsky, Lacey B. and Rhodes, Cassie L. and Horman, Brian M. and Patisaul, Heather B.}, year={2022}, month={Jul}, pages={140–154} }
 @article{gillera_marinello_nelson_horman_patisaul_2022, title={Individual and Combined Effects of Paternal Deprivation and Developmental Exposure to Firemaster 550 on Socio-Emotional Behavior in Prairie Voles}, volume={10}, ISSN={["2305-6304"]}, url={https://doi.org/10.3390/toxics10050268}, DOI={10.3390/toxics10050268}, abstractNote={The prevalence of neurodevelopmental disorders (NDDs) is rapidly rising, suggesting a confluence of environmental factors that are likely contributing, including developmental exposure to environmental contaminants. Unfortunately, chemical exposures and social stressors frequently occur simultaneously in many communities, yet very few studies have sought to establish the combined effects on neurodevelopment or behavior. Social deficits are common to many NDDs, and we and others have shown that exposure to the chemical flame retardant mixture, Firemaster 550 (FM 550), or paternal deprivation impairs social behavior and neural function. Here, we used a spontaneously prosocial animal model, the prairie vole (Microtus ochrogaster), to explore the effects of perinatal chemical (FM 550) exposure alone or in combination with an early life stressor (paternal absence) on prosocial behavior. Dams were exposed to vehicle (sesame oil) or 1000 µg FM 550 orally via food treats from conception through weaning and the paternal absence groups were generated by removing the sires the day after birth. Adult offspring of both sexes were then subjected to open-field, sociability, and a partner preference test. Paternal deprivation (PD)-related effects included increased anxiety, decreased sociability, and impaired pair-bonding in both sexes. FM 550 effects include heightened anxiety and partner preference in females but reduced partner preference in males. The combination of FM 550 exposure and PD did not exacerbate any behaviors in either sex except for distance traveled by females in the partner preference test and, to a lesser extent, time spent with, and the number of visits to the non-social stimulus by males in the sociability test. FM 550 ameliorated the impacts of parental deprivation on partner preference behaviors in both sexes. This study is significant because it provides evidence that chemical and social stressors can have unique behavioral effects that differ by sex but may not produce worse outcomes in combination.}, number={5}, journal={TOXICS}, author={Gillera, Sagi Enicole A. and Marinello, William P. and Nelson, Mason A. and Horman, Brian M. and Patisaul, Heather B.}, year={2022}, month={May} }
 @article{gillera_marinello_cao_horman_stapleton_patisaul_2021, title={Sex-specific Disruption of the Prairie Vole Hypothalamus by Developmental Exposure to a Flame Retardant Mixture}, volume={162}, ISSN={["1945-7170"]}, url={http://dx.doi.org/10.1210/endocr/bqab100}, DOI={10.1210/endocr/bqab100}, abstractNote={Abstract}, number={8}, journal={ENDOCRINOLOGY}, publisher={The Endocrine Society}, author={Gillera, Sagi Enicole A. and Marinello, William P. and Cao, Kevin T. and Horman, Brian M. and Stapleton, Heather M. and Patisaul, Heather B.}, year={2021}, month={Aug} }
 @article{developmental exposure to tetrabromobisphenol a has minimal impact on male rat reproductive health._2020, url={https://doi.org/10.1016/j.reprotox.2020.05.003}, DOI={10.1016/j.reprotox.2020.05.003}, abstractNote={The flame retardant and plasticizer, tetrabromobisphenol-A (TBBPA) has rapidly become a common component in the manufacture of circuit boards and plastics worldwide. It is also an analog of bisphenol A (BPA), an endocrine disrupting chemical identified by the Endocrine Society. As such, TBBPA needs to be investigated for similar potential human health risks. Using rats as a model, we exposed pregnant dams and their progeny to 0, 0.1, 25, or 250 mg TBBPA/kg of body weight until the offspring reached adulthood and assessed the first generation of males for any reproductive tract abnormalities. We found no differences in the morphology of testes, sperm, prostates, or secondary sex organs from post-natal day 21 through one-year of age. A delay in the time to preputial separation was found with the 250 mg/kg treatment. Also, minor differences of sperm count at one-year old with the 25 mg/kg treatment and expression levels of two steroidogenic pathway enzymes at either post-natal day 90 or one-year old in the 250 mg/kg treatment group were detected, but spermatogenesis was not disrupted. While these results may lead to the supposition that TBBPA is less harmful than its parent compound BPA, more studies need to be conducted to assess long-term exposure effects.}, journal={Reproductive toxicology (Elmsford, N.Y.)}, year={2020}, month={May} }
 @article{rock_gillera_devarasetty_horman_knudsen_birnbaum_fenton_heather_2019, title={Sex-specific behavioral effects following developmental exposure to tetrabromobisphenol A (TBBPA) in Wistar rats}, volume={75}, ISSN={["1872-9711"]}, url={https://doi.org/10.1016/j.neuro.2019.09.003}, DOI={10.1016/j.neuro.2019.09.003}, abstractNote={Tetrabromobisphenol A (TBBPA) has become a ubiquitous indoor contaminant due to its widespread use as an additive flame retardant in consumer products. Reported evidence of endocrine disruption and accumulation of TBBPA in brain tissue has raised concerns regarding its potential effects on neurodevelopment and behavior. The goal of the present study was to examine the impact of developmental TBBPA exposure, across a wide range of doses, on sexually dimorphic non-reproductive behaviors in male and female Wistar rats. We first ran a pilot study using a single TBBPA dose hypothesized to produce behavioral effects. Wistar rat dams were orally exposed using cookie treats to 0 or 0.1 mg TBBPA/kg bw daily from gestational day (GD) 9 to postnatal day (PND) 21 to assess offspring (both sexes) activity and anxiety-related behaviors. Significant effects were evident in females, with exposure increasing activity levels. Thus, this dose was used as the lowest TBBPA dose in a subsequent, larger study conducted as part of a comprehensive assessment of TBBPA toxicity. Animals were exposed to 0, 0.1, 25, or 250 mg TBBPA/kg bw daily by oral gavage starting on GD 6 through PND 90 (dosed dams GD 6 - PND 21, dosed offspring PND 22 - PND 90). Significant behavioral findings were observed for male offspring, with increased anxiety-like behavior as the primary phenotype. These findings demonstrate that exposure to environmental contaminants, like TBBPA, can have sex-specific effects on behavior highlighting the vulnerability of the developing brain.}, journal={NEUROTOXICOLOGY}, publisher={Elsevier BV}, author={Rock, Kylie D. and Gillera, Sagi Enicole A. and Devarasetty, Pratyush and Horman, Brian and Knudsen, Gabriel and Birnbaum, Linda S. and Fenton, Suzanne E. and Heather, Patisaul B.}, year={2019}, month={Dec}, pages={136–147} }
 @article{gillera_marinello_horman_phillips_ruis_stapleton_reif_patisaul_2019, title={Sex-specific effects of perinatal FireMaster® 550 (FM 550) exposure on socioemotional behavior in prairie voles.}, volume={79}, url={https://doi.org/10.1016/j.ntt.2019.106840}, DOI={10.1016/j.ntt.2019.106840}, abstractNote={The rapidly rising incidence of neurodevelopmental disorders with social deficits is raising concern that developmental exposure to environmental contaminants may be contributory. Firemaster 550 (FM 550) is one of the most prevalent flame-retardant (FR) mixtures used in foam-based furniture and baby products and contains both brominated and organophosphate components. We and others have published evidence of developmental neurotoxicity and sex specific effects of FM 550 on anxiety-like and exploratory behaviors. Using a prosocial animal model, we investigated the impact of perinatal FM 550 exposure on a range of socioemotional behaviors including anxiety, attachment, and memory. Virtually unknown to toxicologists, but widely used in the behavioral neurosciences, the prairie vole (Microtus ochrogaster) is a uniquely valuable model organism for examining environmental factors on sociality because this species is spontaneously prosocial, biparental, and displays attachment behaviors including pair bonding. Dams were exposed to 0, 500, 1000, or 2000 μg of FM 550 via subcutaneous (sc) injections throughout gestation, and pups were directly exposed beginning the day after birth until weaning. Adult offspring of both sexes were then subjected to multiple tasks including open field, novel object recognition, and partner preference. Effects were dose responsive and sex-specific, with females more greatly affected. Exposure-related outcomes in females included elevated anxiety, decreased social interaction, decreased exploratory motivation, and aversion to novelty. Exposed males also had social deficits, with males in all three dose groups failing to show a partner preference. Our studies demonstrate the utility of the prairie vole for investigating the impact of chemical exposures on social behavior and support the hypothesis that developmental FR exposure impacts the social brain. Future studies will probe the possible mechanisms by which these effects arise.}, journal={Neurotoxicology and teratology}, publisher={Elsevier BV}, author={Gillera, Sagi Enicole A. and Marinello, William P. and Horman, Brian M. and Phillips, Allison L. and Ruis, Matthew T. and Stapleton, Heather M. and Reif, David M. and Patisaul, Heather B.}, year={2019}, month={Nov}, pages={106840} }