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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.

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.

Prenatal exposure to endocrine disrupting chemicals (EDCs) has been shown to produce a predisposition to behavioral disorders in later life. Bisphenol A (BPA) and di(2‐ethylhexyl) phthalate (DEHP) are two widely prevalent EDCs in the environment and exposure to these chemicals is unavoidable. We examined if prenatal exposure to these chemicals would produce behavioral changes in offspring. Female rats were orally administered BPA (B; 5 μg/kg body weight), DEHP (D; 7.5 mg/kg body weight), a combination of BPA and DEHP (B+D), or saline (control; 10 μL/kg body weight) during days 6 through 21 of pregnancy. Adult offspring underwent a battery of behavioral tests consisting of the open field task (OFT), elevated plus maze (EPM), and shock probe defensive burying (SPDB). In the OFT, control and B+D‐treated females spent a significantly lower percentage of time in the center zone than control males. These sex differences were not observed in B‐ or D‐treated animals, however, both male and female D‐offspring spent significantly less time in the center compared to control males. In the EPM, B animals displayed sex differences that were not present in control animals, with B females spending significantly more time in the open arms compared to both control and B males. D and B+D animals were not significantly different from controls in time spent in the open arms. No differences were seen in total exploration of the OFT or EPM. Control female animals reared and explored the probe significantly more than control males during SPDB. Sex differences were not present in B‐ or B+D‐treated offspring and were altered in D‐treated offspring. B‐treated female offspring buried less than control female offspring, but did not differ in immobility time or frequency of rearing or probe exploration in the SPDB, indicating a less robust response to threat. B treated male offspring were no different than control male offspring in the SPDB. D‐treated female offspring reared and explored the probe fewer times than female control‐treated offspring. Behavior was similar to control male offspring for each behavior, suggesting a masculinization of behavioral response to threat. D‐treated male offspring buried significantly less and spent significantly more time immobile than control males, suggesting a phenotypic shift to a passive‐coping style in response to threat. Finally, male and female B+D offspring showed a similar behavioral phenotype during SPDB. In conclusion, these results demonstrate that prenatal exposure to EDCs differentially alters behavior in male and female rats.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.