Prenatal EDC Exposure Followed by Chronic Treatment with Estradiol Affects Brain Monoamine Levels in Female Rats

Abstract

In utero exposure to low doses of endocrine disrupting chemicals (EDCs), in particular the widely prevalent plasticizers bisphenol A (BPA) and di(2‐ethylhexyl) phthalate (DEHP), has been shown to produce long‐lasting behavioral effects in rats. Additionally, changes in estrogen are associated with the development of affective disorders in women; however, the underlying neurobiological mechanisms are unclear. A previous study from our lab found that chronic estradiol treatment led to decreased dopamine (DA) levels within the central amygdala (CeA). This study was conducted to further examine the cumulative effects of prenatal exposure to EDCs followed by chronic estradiol exposure in adult female rats on DA levels in stress‐related brain areas. Dams were orally administered saline (control; 10 μL/kg), BPA (B; 5 μg/kg), DEHP (D; 7.5 mg/kg) or a combination of BPA+DEHP (B+D) during days 6 through 21 of pregnancy. Adult female offspring were sham‐implanted or implanted with pellets that release 17β‐estradiol (E2) for 90 days (20 ng/day; Innovative Research America). The offspring then underwent a battery of behavioral tests at the end of treatment. Brains collected from the offspring were sectioned and the CeA, hippocampus (HC), and prefrontal cortex (PFC) were microdissected and analyzed for levels of DA using High‐Performance Liquid Chromatography (HPLC). Prenatal exposure to DEHP and/or B+D, but not B, was significantly associated with reductions in DA levels in the CeA and PFC. Within the CeA, only B+D‐E2 treated offspring showed a significant decrease in DA (p<0.05) in comparison with control offspring. Levels of DA were found to be lower in the PFC as well, particularly in D‐sham (p<0.05), D‐E2 (p<0.01), and B+D‐E2 (p<0.05) offspring compared to controls. No differences were observed in hippocampal DA levels in any of the treatment groups. These results indicate that prenatal exposure to DEHP or a mixture of EDCs in females may lead to alterations in monoamine levels in a region‐specific manner, and E2 treatment in adulthood may exacerbate these effects.Support or Funding InformationUniversity of Georgia Research Foundation and start‐up funds.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.