DEP and DBP induce cytotoxicity in mouse embryonic stem cells and abnormally enhance neural ectoderm development. (May 2018)

• Record Type: Journal Article
• Authors: Yin, Nuoya; Liang, Shengxian; Liang, Shaojun; Hu, Bowen; Yang, Renjun; Zhou, Qunfang; Jiang, Guibin; Faiola, Francesco
• Is Part Of: Environmental pollution. Volume 236(2018)
• Page Start: 21
• Page End: 32
• Publication Date: 2018-05
• Subjects: DEP -- DBP -- Embryonic stem cell -- Developmental neural toxicity -- Phthalate; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2018.01.035
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Diethyl phthalate (DEP) and dibutyl phthalate (DBP) are two typical small phthalate esters, extensively used in personal care and consumer products. Although previous studies have linked phthalate esters to several health issues, it is still unclear whether they can affects the early stages of embryonic development. In this study, we evaluated the early developmental neurotoxicity as well as the cytotoxicity of DEP and DBP, using mouse embryonic stem cells (mESCs). Our results showed that both DEP and DBP could decrease mESC viability in a dose-dependent manner. Moreover, while DBP could activate the caspase-3/7 enzymes and cause cell membrane damage as well as intracellular ROS accumulation, interestingly DEP treatment only showed stimulation of ROS production. In addition, DEP and DBP treatment at non-cytotoxic concentrations, abnormally altered the expression levels of several vitally important regulators of embryo development. For instance, neural ectoderm markers, such as Pax6, Nestin, Sox1 and Sox3, were significantly up-regulated upon DEP and DBP exposure. In conclusion, our work suggests a potential developmental toxicity of DEP and DBP on mammals, especially for neural ectoderm specification. Our findings help better understand the association between health problems and DEP/DBP exposure and most significantly remind us of the importance of additional health risk tests for these two largely used chemicals. Graphical abstract: Image 1 Highlights: DEP and DBP decrease viability of mESCs in a dose-dependent manner. DBP induces apoptosis, membrane damage and ROS accumulation in mESCs. DEP and DBP disturb the differentiation process of mESCs. DEP and DBP abnormally enhance neural-ectoderm development at non-cytotoxic concentrations. Abstract : Our results directly provide evidence of the potential developmental neural toxicity of the two phthalate esters, DEP and DBP, which was not emphasized enough before.