Di-(2-ethylhexyl) phthalate upregulates ATF3 expression and suppresses apoptosis in mouse genital tubercle.
OBJECTIVE
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.
Liu
Xing
X
Department of Pediatric Urology, Chongqing Children's Hospital, Chongqing, China.
Zhang
De-Ying
DY
Li
Ya-Sha
YS
Xiong
Jing
J
He
Da-Wei
DW
Lin
Tao
T
Li
Xu-Liang
XL
Wei
Guang-Hui
GH
D051700:Activating Transcription Factor 3 / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D003314:Corn Oil / Q000737:chemistry / Q000633:toxicity; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D005837:Genitalia, Male / Q000187:drug effects*; D007021:Hypospadias / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000187:drug effects
D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D010968:Plasticizers; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D003314:Corn Oil; D004051:Diethylhexyl Phthalate