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Neuroscience. 2011 Oct 13;193:100-8. doi: 10.1016/j.neuroscience.2011.06.082. Epub 2011 Jul 18.

Acute postnatal exposure to di(2-ethylhexyl) phthalate adversely impacts hippocampal development in the male rat.

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Department of Neuroscience, Carleton University, Ottawa, ON K1S5B6, Canada.


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.

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