Altered Hippocampal Lipid Profile Following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Rats

Abstract

Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl) phthalate (DEHP) disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females.

Neural Mechanisms Underlying the Disruption of Male Courtship Behavior by Adult Exposure to Di(2-ethylhexyl) Phthalate in Mice

“…Indeed, among the rodent studies addressing the effects of DEHP exposure in males, only four works were dedicated to adult exposure and its potential impact on the rat testis ( Agarwal et al 1986 ; Dostal et al 1988 ; Guo et al 2013 ; Li et al 2012 ), while no data are available on brain and behavior in rat or mice. Our results on the impact of low doses of DEHP may be also informative, as most studies on DEHP-induced effects on the nervous system used higher doses of this molecule in mice ( Komada et al 2016 ; Tanaka 2002 ; Tanaka 2005 ; Tanida et al 2009 ; Xu et al 2015 ) and rat ( Carbone et al 2010 ; Carbone et al 2013 ; Smith et al 2011 , 2015 ; Smith and Holahan 2014 ; Lin et al 2015 ).…”

Metabolomic Markers of Phthalate Exposure in Plasma and Urine of Pregnant Women

“…In addition, several correlating sphingolipids such as ceramide, ceramide-1-phosphate, sphingosine, and sphingosine-1-phosphate may serve as signaling molecules that influence obesity, diabetes, metabolic syndrome ( 56 – 58 ), oxidative stress and inflammatory signaling ( 59 ). Previous reports describe the effects of phthalates on sphingolipid metabolism in rat brain linked with hippocampal development ( 60 ) and liver toxicity ( 61 ), but additional research is required to understand their role in maternal-neonate health and obesity.…”

Toxic Effects of Di-2-ethylhexyl Phthalate: An Overview

“…Resistance of the female rat hippocampus to modification by DEHP is because DEHP alters the lipid profile of the hippocampus during postnatal development, leading to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats but no effect of DEHP on the abundance of phosphatidylcholine and sphingomyelin in the hippocampus of male rats. These studies suggested that upregulation of hippocampal lipids may serve a neuroprotective role in DEHP-exposed female rats [ 72 ].…”