PMID- 17011747
OWN - NLM
STAT- MEDLINE
DCOM- 20070306
LR  - 20131121
IS  - 0890-6238 (Print)
IS  - 0890-6238 (Linking)
VI  - 23
IP  - 1
DP  - 2007 Jan
TI  - Analysis of gene expression profiles in the offspring of rats following maternal 
      exposure to xenoestrogens.
PG  - 42-54
AB  - Many environmental chemicals are known endocrine disruptors (EDs). These have the 
      potential to alter endocrine systems via various mechanisms that include binding 
      to hormone receptors, thereby either mimicking or blocking the hormone actions 
      and causing abnormal gene expression. Here, to elucidate the molecular 
      mechanism(s) underlying the detrimental effects associated with the estrogenicity 
      of these chemicals, we determined whether gene profiles were altered in rats 
      exposed to 4-tert-octyphenol (OP) and diethylstilbestrol (DES) in utero. Pregnant 
      rats were treated with a high dose of OP (600 mg/kg BW per day) or DES (500 
      microg/kg BW per day) at gestational days (GD) 17, 18 and 19. Both dams and 
      neonates were euthanized at lactation day (LD) 5. The transcript profiles of 
      uterine tissue were compared in treated versus control in both maternal and 
      neonatal sites using cDNA microarray to determine the expression levels of 
      approximately 13,000 genes and expressed sequence tags (ESTs). The expression 
      levels of some known estrogen-responsive genes, i.e., complement component 3, 
      epidermal growth factor receptor or c-fos oncogene and calbindin 3, as well as 
      some other randomly selected genes, including general transcription factor IIa, 
      transcription factor 4 and lymphocyte specific 1, were increased by OP and/or DES 
      treatment in the uteri of both maternal and neonate groups. However, the 
      magnitude of these alterations in gene expression differed markedly between dams 
      and neonates, most likely reflecting the temporal susceptibility of the 
      reproductive tract to estrogenic chemicals. Importantly, the altered gene 
      patterns identified by microarray analysis were confirmed by RT-PCR and real-time 
      RT-PCR. Fifteen primers were designed to amplify specific altered genes. These 
      genes were selected for validation because of their markedly increased expression 
      levels and they were classified on the basis of gene ontology. Overall, a high 
      correlation was observed between microarray and real-time PCR data. Taken 
      together, these results indicate that placental exposure to OP or DES may cause 
      temporal changes in gene expression in the uteri of dams and neonates. Moreover, 
      these findings may provide useful indicators of the adverse effects of EDs and 
      prove particularly important in elucidating the effects of xenoestrogens on 
      estrogen-responsive tissues, such as the developing reproductive tract.
FAU - Dang, Vu Hoang
AU  - Dang VH
AD  - Laboratory of Veterinary Biochemistry and Molecular Biology, College of 
      Veterinary Medicine, Research Institute of Veterinary Medicine, Chungbuk National 
      University, Cheongju, Chungbuk 361-763, Republic of Korea.
FAU - Choi, Kyung-Chul
AU  - Choi KC
FAU - Hyun, Sang-Hwan
AU  - Hyun SH
FAU - Jeung, Eui-Bae
AU  - Jeung EB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060903
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Estrogens, Non-Steroidal)
RN  - 0 (Phenols)
RN  - 0 (RNA, Messenger)
RN  - 0 (Surface-Active Agents)
RN  - 731DCA35BT (Diethylstilbestrol)
RN  - IOY9FVU3J3 (4-tert-octylphenol)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Diethylstilbestrol/adverse effects
MH  - Estrogen Antagonists/*adverse effects
MH  - Estrogens, Non-Steroidal/adverse effects
MH  - Female
MH  - Gene Expression/*drug effects
MH  - *Gene Expression Profiling
MH  - Male
MH  - Maternal Exposure/*adverse effects
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phenols/*adverse effects
MH  - Pregnancy
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Surface-Active Agents/*adverse effects
MH  - Uterus/drug effects/metabolism
EDAT- 2006/10/03 09:00
MHDA- 2007/03/07 09:00
CRDT- 2006/10/03 09:00
PHST- 2006/04/21 00:00 [received]
PHST- 2006/08/25 00:00 [revised]
PHST- 2006/08/29 00:00 [accepted]
PHST- 2006/10/03 09:00 [pubmed]
PHST- 2007/03/07 09:00 [medline]
PHST- 2006/10/03 09:00 [entrez]
AID - S0890-6238(06)00206-1 [pii]
AID - 10.1016/j.reprotox.2006.08.010 [doi]
PST - ppublish
SO  - Reprod Toxicol. 2007 Jan;23(1):42-54. doi: 10.1016/j.reprotox.2006.08.010. Epub 
      2006 Sep 3.