Sex Specific Disruption of Estrogen Receptor Alpha (ERα) Density in the Social Brain Neural Network by Firemaster 550

Abstract We investigated how developmental exposure to the commercial flame retardant (FR) mixture Firemaster 550 (FM 550) affects estrogen receptor alpha (ERα) expression in key brain regions related to sociosexual behavior. We used prairie voles, a socially monogamous, biparental rodent species of high translational human relevance. This study used adult siblings from a prior behavioral study showing developmental FM 550 exposure impaired a range of socioemotional behaviors in adults including loss of partner preference in males. Dams were exposed to FM 550 (500, 1000, or 2000 µg/day) via subcutaneous (sc) injections throughout gestation, and pups were directly exposed from birth to weaning. ERα immunoreactive (ERα-ir) neuron numbers and mRNA expression levels were quantified in subregions of the social brain neural network (SBNN). As anticipated, FM 550 impacts were sex, dose, and region specific, with FM 550 tending to increase ERα-ir cell numbers in the anterior hypothalamus regardless of sex, but decrease them in the female mediobasal hypothalamus, amygdala and extended amygdala. These studies demonstrate that developmental FR exposure impacts adult SBNN ERα availability and provide support that disrupted ERα action in the SBNN may be a mechanism underlying disruption of socioemotional behavior, energy balance, and related neuroendocrine physiology. Impacted ERα neuronal populations are also influenced by other receptors, neuropeptides, neurosteroids and signaling molecules to govern prosocial behaviors, which is the ongoing direction of this work. Collectively, these data add to growing evidence that FM 550 FRs are neuroendocrine disruptors that can induce persistent impacts across developing socioemotional pathways and systems.