Di-(2-Ethylhexyl) Phthalate Upregulates Atf3 Expression and Suppresses Apoptosis in Mouse Genital Tubercle

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作者：Liu, X., Zhang, D. Y., Li, Y. S., Xiong, J., He, D. W., Lin, T., Li, X. L. & Wei, G. H.
期刊：Journal of occupational health 51, 57-63 (2009)
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OBJECTIVES: To investigate the effect of di-(2-ethylhexyl) phthalate (DEHP) on the expression of activating transcription factor 3 (ATF3) and apoptosis of fetal mouse genital tubercle (GT). METHODS: In this developmental toxicity study, pregnant C57BL/6 mice were exposed to corn oil or DEHP (100 or 500 mg/kg/day) from embryonic day 12 (ED12) to ED16. Apoptosis was characterized by Terminal transferase dUTP nick end labeling (TUNEL) assay. Using RT-PCR and western blot, the expressions of ATF3 and apoptosis-related genes (P53, Bcl-2 and Bax) were investigated. RESULTS: Apoptosis of fetal mouse GT cells notably decreased after DEHP treatment. DEHP activated ATF3 both at the mRNA and protein levels in GT. Furthermore, pro-apoptotic P53 was downregulated and the ratio of anti-apoptotic (Bcl-2)/pro-apoptotic (Bax) was not significantly changed. CONCLUSIONS: These results suggest that DEHP may induce external genital defects via a mechanism involving apoptosis, which might correlate with the regulation of ATF3 and P53 expressions.