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Acute postnatal exposure to di(2-ethylhexyl) phthalate adversely impacts hippocampal development in the male rat
C A Smith1, A Macdonald, M R Holahan
1Department of Neuroscience, Carleton University, Ottawa, ON K1S5B6, Canada. csmith@connect.carleton.ca
Insights
Early life exposure to di(2-ethylhexyl) phthalate (DEHP) impacts male rat hippocampus development, reducing axonal markers and neuron density. Female rats showed no significant effects from the same phthalate exposure.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Phthalate exposure during early life is linked to reproductive toxicity.
- Limited data exists on phthalates' effects on brain development.
- Hippocampal axonal fields undergo significant changes during early postnatal development.
Purpose of the Study:
- To investigate the impact of acute phthalate exposure on hippocampal development.
- To assess morphological outcomes in male and female rats during a critical developmental window (postnatal days 16-22).
Main Methods:
- Exposure of Long Evans rats to di(2-ethylhexyl) phthalate (DEHP; 10 mg/kg, i.p.) from postnatal day 16 to 22.
- Analysis of axonal markers in the CA3 region.
- Assessment of cell density in the dentate gyrus (DG) and CA3 areas.
Main Results:
- DEHP exposure reduced axonal markers in the CA3 distal stratum oriens (SO) of male rats.
- Cell density of immature neurons in the DG and mature neurons in the CA3 was reduced in male rats.
- No significant morphological differences were observed in the hippocampus of female rats exposed to DEHP compared to controls.
Conclusions:
- Di(2-ethylhexyl) phthalate (DEHP) negatively impacts male hippocampal development.
- Female rats appear less vulnerable to DEHP's effects on hippocampal morphology during this developmental period.
- Further research is recommended on phthalate exposure during critical neurodevelopmental stages.
Abstract:
The distribution of CA3 hippocampal axonal terminal fields undergo a period of widespread connectivity-based changes in the early postnatal stages of life. The purpose of the current study was to examine the effect of acute phthalate exposure during this period of hippocampal development (postnatal days 16-22 (p16-p22)) on morphological outcomes in male and female Long Evans rats. The reproductive toxicity of exposure to phthalates early in life has been well-documented; however, much less is known about the effects of phthalates on brain development. The present research demonstrated that exposure to di(2-ethylhexyl) phthalate (DEHP; 10 mg/kg, i.p.) from p16 to p22 reduced axonal markers in the CA3 distal stratum oriens (SO) and reduced cell density of both immature and mature neurons in the dentate gyrus (DG) and CA3, respectively, in male rats. The same markers in the hippocampus of female rats were similar in saline and DEHP-treated animals. These data suggest that DEHP has a negative impact on the development of the hippocampus in males but not females and recommend more extensive animal studies on phthalate exposure during the vulnerable post-natal developmental period when rapid structural and functional changes are taking place.
