Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants and are ubiquitous environmental toxins, detectible at some level in ∼100% of women. Prior studies have suggested that PBDEs enhance placental inflammation, a known risk factor for neurodevelopmental disorders like autism. Therefore, our objective was to determine if in utero exposure to PBDE results in autism-like behaviors in offspring in an inflammation-dependent manner.
An IACAC-approved 2 x 2 factorial study design was implemented. Pregnant Wistar rats were assigned to one of 4 groups: control (VEH) without LPS, VEH with LPS, PBDE-209 without LPS, and PBDE-209 with LPS. Rats were received on gestational day (GD)3 and treated daily with cornflakes containing either PBDE-209 (1 mg/kg in corn oil) or VEH (corn oil alone) until delivery (GD23-24). On GD9, half of the dams of each group received LPS (100 mcg/kg intraperitoneally) or an equivalent volume of sterile saline (PBS). Pups from each litter underwent behavioral testing (open field and novel object) at post-natal day (PND)30 or PND60. Entries into center vs peripheral regions of the open field and interactions with or time spent with the novel object were recorded. Data was analyzed with generalized estimating equations. P < 0.05 was considered statistically significant.
Of 24 dams, 17 of them delivered 162 pups. LPS-treated dams weighed less at GD16 than PBS-treated dams (P=0.009). LPS and PBDE reduced PND9 pup weights (P=0.018). For open field testing, there were no significant differences at PND30 for time spent in peripheral regions, entries into peripheral regions, time spent in center regions, or entries into center regions. At PND60, LPS increased entries into central regions but PBDE reduced the number of entries (P=0.03) in LPS-treated rats. Between 78–100% of pups interacted with the novel object, more at PND60. Of the pups interacting with the novel object, PBDE exposure reduced the time to first encounter (P=0.03).
In utero exposure to LPS, PBDE-209, or both did not cause the expected autism-like behaviors in the offspring. However, PBDE-treatment significantly reduced the weights of the pups of LPS-treated dams, suggesting some adverse effects on pregnancy outcome.
© 2018 Published by Elsevier Inc.