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Prenatal programming with endocrine disrupting chemicals (EDCs), in particular the ubiquitous plasticizers bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP), can induce long-lasting behavioral changes in rats. Additionally, changes in estrogen are correlated with the development of mood disorders in women; however, the underlying neurobiological mechanisms are unclear. This study was conducted to determine the cumulative effects of prenatal exposure to EDCs followed by chronic estradiol treatment in adult female rats on monoamine levels in the prefrontal cortex (PFC) and hippocampus (HC). 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 PFC and HC were microdissected and analyzed for levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT), using High-Performance Liquid Chromatography (HPLC). Significant reductions in monoamine levels were observed in the PFC while NE and 5-HT levels were markedly reduced in the HC after prenatal exposure to D or BD. BPA’s effects on monoamines were comparatively modest. E2 exposure increased DA but decreased 5-HT levels in the PFC of control animals. Prenatal exposure to EDCs made the offspring non-responsive to E2. The marked reduction in monoamine levels could have implications for learning and memory.

Bisphenol A (BPA) and Diethylhexyl Phthalate (DEHP) are common environmental endocrine disrupting chemicals (EDCs) that exert a range of potential adverse health effects. EDC exposure can occur in utero and during early postnatal life, when organ systems are differentiating resulting in a number of disorders in adulthood. The aim of this study was to evaluate the immunotoxic effect of prenatal exposure to individual and combinations of BPA and DEHP on male and female rat thymus. From gestational day 6 till 21, Sprague Dawley dams were orally administered either saline (control; n=7), BPA (5μg/Kg BW; n=7), DEHP (7.5mg/Kg BW; n=7), or a mixture of BPA and DEHP (B+D; n=7). Male and female offspring were sacrificed at 16 weeks of age. Thymus and spleen were dissected, weighed, and stored for further processing. Our data showed that spleen weight to body weight (BW) ratio of EDC treated offspring were comparable to those from age‐matched control rats. However, male offspring (but not females) that were prenatally exposed to BPA alone exhibited a 40% decrease (p<0.01) and those exposed to DEHP alone had a 27% reduction in thymus/BW ratio (p<0.05). To understand if prenatal EDC exposure was promoting early thymus involution through apoptosis, we performed Terminal deoxynucleotidyl transferase‐dUTP nick end labeling (TUNEL) staining of nicked DNA on thymic sections. There was significant apoptosis in the thymic cortex in both male and female offspring that were prenatally exposed to individual EDCs. Apoptosis was hardly detected in the medullary region. Apoptosis in the B+D group was markedly reduced compared to individual EDC exposures. These results suggest that prenatal exposure to even low BPA and moderate DEHP levels can promote apoptosis in the thymus. This could possibly affect immune functions in adulthood. Interestingly, exposure to a mixture of these EDCs did not produce any significant change in apoptosis in the thymus.Support or Funding InformationSupported by UGA 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.