Sex Differences in the Effects of Prenatal Exposure to Low Doses of Endocrine Disruptors on Stress‐Related Behavior

Abstract

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.