Developmental exposure to the Fox River PCB mixture modulates behavior in juvenile mice

Developmental exposures to PCBs are implicated in the etiology of
neurodevelopmental disorders (NDDs). This observation is concerning given
the continued presence of PCBs in the human environment and the increasing
incidence of NDDs. Previous studies reported that developmental exposure
to legacy commercial PCB mixtures (Aroclors) or single PCB congeners found
in Aroclors caused NDD-relevant behavioral phenotypes in animal models.
However, the PCB congener profile in contemporary human samples is
dissimilar to that of the legacy Aroclors, raising the question of whether
human-relevant PCB mixtures similarly interfere with normal brain
development. To address this question, we assessed the developmental
neurotoxicity of the Fox River Mixture (FRM), which was designed to mimic
the congener profile identified in fish from the PCB-contaminated Fox
River that constitute a primary protein source in the diet of surrounding
communities. Adult female C57BL/6 J mouse dams (8-10 weeks old) were
exposed to vehicle (peanut oil) or FRM at 0.1, 1.0, or 6.0 mg/kg/d in
their diet throughout gestation and lactation, and neurodevelopmental
outcomes were assessed in their pups. Ultrasonic vocalizations (USVs) and
measures of general development were quantified at postnatal day (P) 7,
while performance in the spontaneous alternation task and the 3-chambered
social approach/social novelty task was assessed on P35. Triiodothyronine
(T3) and thyroxine (T4) were quantified in serum collected from the dams
when pups were weaned and from pups on P28 and P35. Developmental exposure
to FRM did not alter pup weight or body temperature on P7, but USVs were
significantly decreased in litters exposed to FRM at 0.1 or 6.0 mg/kg/d in
the maternal diet. FRM also impaired male and female pups'
performance in the social novelty task. Compared to sex-matched vehicles,
significantly decreased social novelty was observed in male and female
pups in the 0.1 and 6.0 mg/kg/d dose groups. FRM did not alter performance
in the spontaneous alternation or social approach tasks. FRM increased
serum T3 levels but decreased serum T4 levels in P28 male pups in the 1.0
and 6.0 mg/kg/d dose groups. In P35 female pups and dams, serum T3 levels
decreased in the 6.0 mg/kg/d dose group while T4 levels were not altered.
Collectively, these findings suggest that FRM interferes with the
development of social communication and social novelty, but not memory,
supporting the hypothesis that contemporary PCB exposures pose a risk to
the developing brain. FRM had sex, age, and dose-dependent effects on
serum thyroid hormone levels that overlapped but did not perfectly align
with the FRM effects on behavioral outcomes. These observations suggest
that changes in thyroid hormone levels are not likely the major factor
underlying the behavioral deficits observed in FRM-exposed animals.