Perinatal exposure to benzyl butyl phthalate induces alterations in neuronal development/maturation protein expression, estrogen responses, and fear conditioning in rodents

Abstract

Phthalate exposure has recently been associated with behavioral actions that are linked to its endocrine-disrupting properties. The purpose of this study was to investigate the molecular, anatomical, and behavioral effects of indirect perinatal benzyl butyl phthalate (BBP) exposure in offspring of BBP-treated pregnant dams. In two separate experiments, we administered BBP (10.0 μg/ml) on food pellets to pregnant dams and examined the offspring. The first experiment revealed reproductive anatomical abnormalities linked to BBP's endocrine-disrupting properties, whereas histological analysis revealed preserved hippocampal neuronal migration. The second experiment demonstrated learning and memory impairments accompanied by molecular abnormalities in multiple brain regions. Offspring from BBP-treated dams had altered levels of several proteins important for neuronal circuitry formation, tissue development, and maturation. We suggest that BBP administration disrupts normal learning and that these effects could be related to alterations in brain development and result in a phenotype similar to that observed in neurodevelopmental disorders.

Behavioral Effects of Exposure to Phthalates in Female Rodents: Evidence for Endocrine Disruption?

“…Four other studies assessed the effects of exposure to lower doses of phthalates with BBP at 10 µg/kg/d, DEHP at 33 mg/kg/d, or a phthalate mixture at 0.2 to 1 mg/kg/d on aversive stimulus associated learning [ 82 ], object recognition memory [ 83 ], and cognitive flexibility [ 72 , 84 ], respectively. In mice, the novel object recognition test indicated a higher preference for the novel object in mice exposed to 200 mg/kg/d [ 83 ].…”

“…In the aversive-stimulus associative test, a shorter duration of freezing during the interval period and the tone period was observed in rats exposed to BBP at 10 µg/kg/d [ 82 ]. Analyses of the hippocampus and amygdala, the two regions involved in this behavior, showed increased amounts of synapsin-1 in the dorsal hippocampus and lower amounts of ERα and MeCP2 protein in the amygdala [ 82 ].…”

“…In the aversive-stimulus associative test, a shorter duration of freezing during the interval period and the tone period was observed in rats exposed to BBP at 10 µg/kg/d [ 82 ]. Analyses of the hippocampus and amygdala, the two regions involved in this behavior, showed increased amounts of synapsin-1 in the dorsal hippocampus and lower amounts of ERα and MeCP2 protein in the amygdala [ 82 ]. These studies suggest that developmental exposure to even relatively low doses of phthalates can alter morphology and cognitive function related to the hippocampus, cortex, and amygdala.…”

The detrimental effect of microplastics on critical periods of development in the neuroendocrine system

“…A model of maternal perinatal exposure to BBP was performed in rodents by the group of DeBartolo and colleagues (DeBartolo et al, 2016). In this study, it was observed that the BBP‐exposed offspring had learning and memory impairments, that were accompanied by molecular abnormalities in multiple brain regions (DeBartolo et al, 2016).…”

“…A model of maternal perinatal exposure to BBP was performed in rodents by the group of DeBartolo and colleagues (DeBartolo et al, 2016). In this study, it was observed that the BBP‐exposed offspring had learning and memory impairments, that were accompanied by molecular abnormalities in multiple brain regions (DeBartolo et al, 2016). On the other hand, in order to make an exposure model closer to what happens with the daily use of plastics, Kougias, Sellinger, Willing, and Juraska (2018) performed in rats an experimental approach to evaluate the long‐term neurological effects derived from perinatal exposure to an environmentally relevant mixture of phthalates.…”