Prior work from this lab and others has revealed that perinatal exposure to bisphenol A (BPA) alters sociosexual and mood-related behaviors in rodents, primates, and humans in ways which are age and sex specific. These data suggest that developmental exposure to BPA and other endocrine disrupting compounds (EDCs) might be contributing to the growing prevalence of anxiety- and mood-related disorders in children and adults. Preliminary data from this laboratory reveal that many of these adverse behavioral effects do not manifest in Wistar rats maintained on a soy-rich diet, suggesting that soy isoflavones, such as genistein (GEN) have potentially counteracting effects. What remains to be determined, and will be the focus of the proposed work, is (1) if adoption of a soy-rich diet, either simultaneously or after BPA exposure can mitigate the adverse behavioral effects across the lifespan (2) if the individual isoflavone genistein (GEN) alone is sufficient to induce the counteracting effects and (3) if soy itself (in the absence of BPA) can induce behavioral changes. The latter is critical given the growing prevalence of soy infant formula. Thus, the experiments proposed herein will test the hypothesis that isoflavone consumption, even after BPA exposure has occurred, may help """"""""undo"""""""" the deleterious behavioral effects of BPA. It is further hypothesized that BPA is not acting as an estrogen mimic, but rather, via an epigenetic mechanism. To test these possibilities animals will undergo behavioral assessment in juvenile and adult life and a high throughput approach will be used to identify both neural and transcriptional changes within key hypothalamic regions (amygdala, bed nucleus of the stria terminalis and medial preoptic area) accompanying the effects. The proposed studies have the potential to uncover novel mechanisms of BPA action within neurobehavioral pathways, including those not directly mediated by ERs, and how they might be mitigated by soy isoflavones such as GEN.
Specific Aim 1 seeks to determine the degree to which consumption of a soy-rich diet or GEN can mitigate the sociosexual effects of developmental BPA exposure.
Specific Aim 2 will explore the molecular mechanisms by which soy intake counters BPA effects by assessing the hypothalamic gene expression and DNA methylation changes that correlate with observed behavioral changes in juvenile and adult life.
Epidemiological data suggest that the incidence of adolescent mental health disorders is increasing and it has been hypothesis that exposure to neuroendocrine disrupting chemicals may be a contributing factor. The goal of this research is explore the hypothesis that perinatal exposure to BPA alters sociosexual behaviors by interfering with development and function of the neuroendocrine pathways which regulate them. We will also test the hypothesis that consumption of an isoflavone-rich soy diet may mitigate these effects via an epigenetic mechanism.
|Patisaul, Heather B (2017) Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours. Proc Nutr Soc 76:130-144|
|Rebuli, Meghan E; Gibson, Paul; Rhodes, Cassie L et al. (2016) Sex differences in microglial colonization and vulnerabilities to endocrine disruption in the social brain. Gen Comp Endocrinol 238:39-46|
|Hicks, Kimani D; Sullivan, Alana W; Cao, Jinyan et al. (2016) Interaction of bisphenol A (BPA) and soy phytoestrogens on sexually dimorphic sociosexual behaviors in male and female rats. Horm Behav 84:121-6|
|Rebuli, Meghan E; Patisaul, Heather B (2016) Assessment of sex specific endocrine disrupting effects in the prenatal and pre-pubertal rodent brain. J Steroid Biochem Mol Biol 160:148-59|
|Cao, Jinyan; Echelberger, Roger; Liu, Min et al. (2015) Soy but not bisphenol A (BPA) or the phytoestrogen genistin alters developmental weight gain and food intake in pregnant rats and their offspring. Reprod Toxicol 58:282-94|
|Sullivan, Alana W; Beach, Elsworth C; Stetzik, Lucas A et al. (2014) A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster). Endocrinology 155:3867-81|
|Patisaul, Heather B; Mabrey, Natalie; Adewale, Heather B et al. (2014) Soy but not bisphenol A (BPA) induces hallmarks of polycystic ovary syndrome (PCOS) and related metabolic co-morbidities in rats. Reprod Toxicol 49:209-18|
|Rebuli, Meghan E; Cao, Jinyan; Sluzas, Emily et al. (2014) Investigation of the effects of subchronic low dose oral exposure to bisphenol A (BPA) and ethinyl estradiol (EE) on estrogen receptor expression in the juvenile and adult female rat hypothalamus. Toxicol Sci 140:190-203|
|Yeo, Michele; Patisaul, Heather; Liedtke, Wolfgang (2013) Decoding the language of epigenetics during neural development is key for understanding development as well as developmental neurotoxicity. Epigenetics 8:1128-32|
|Patisaul, Heather B; Sullivan, Alana W; Radford, Meghan E et al. (2012) Anxiogenic effects of developmental bisphenol A exposure are associated with gene expression changes in the juvenile rat amygdala and mitigated by soy. PLoS One 7:e43890|