PMID- 16414171
OWN - NLM
STAT- MEDLINE
DCOM- 20060407
LR  - 20221025
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 220
IP  - 2-3
DP  - 2006 Mar 15
TI  - Gene expression and estrogen sensitivity in rat uterus after developmental 
      exposure to the polybrominated diphenylether PBDE 99 and PCB.
PG  - 104-16
AB  - Considering the presence of polybrominated diphenylethers (PBDEs) in human milk 
      and cord blood, and the estrogenic activity of some congeners, it is conceivable 
      that PBDEs may interact with developing neuroendocrine systems. We investigated 
      effects of 2,2',4,4',5-pentabromo-DE (PBDE 99), a major congener in human milk, 
      on development of brain and reproductive organs, with focus on estrogen target 
      gene expression. Time-pregnant Long Evans rats were subcutaneously injected with 
      PBDE 99 (1 or 10 mg/kg/day), the PCB mixture Aroclor 1254 (10 mg/kg/day), known 
      to interfere with sexual development, or vehicle, from gestational day (GD) 10 to 
      GD 18. In female offspring, anogenital distance was unaffected by PBDE 99 but 
      increased by Aroclor; puberty (vaginal opening) was not significantly changed. 
      Adult PBDE 99-exposed offspring exhibited unchanged uterine weight but increased 
      ovarian weight. Uterine mRNA levels of estrogen target genes were determined by 
      real-time PCR. Progesterone receptor (PR) mRNA was down-regulated at both PBDE 99 
      doses, estrogen receptor alpha (ER alpha), ER beta and insulin-like growth 
      factor-I (IGF-I) were up-regulated at the lower dose. Aroclor induced different 
      effect patterns. In order to investigate possible changes in sensitivity of 
      target genes to estrogen, some offspring were ovariectomized at 10 weeks of age, 
      s.c. injected with estradiol-17beta (E2, 10 microg/kg) or vehicle at 12 weeks, 
      and sacrificed 6 h later. PBDE 99 dose-dependently reduced the magnitude of IGF-I 
      mRNA induction by E2, and increased the magnitude of ER beta repression. PBDE 99 
      also influenced baseline levels of PR, IGF-I and ER beta mRNAs in ovariectomized, 
      vehicle-injected controls. These data indicate that developmental exposure to 
      PBDE 99 at doses devoid of general toxicity, affects the regulation of estrogen 
      target genes in uterus. Since PBDE 99 was detected in blood and adipose tissue of 
      adult offspring, these effects may result from interactions with developmental 
      processes, adult functions, or a combination of both.
FAU - Ceccatelli, Raffaella
AU  - Ceccatelli R
AD  - GREEN Tox and Institute of Pharmacology and Toxicology, University of Zurich, 
      Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
FAU - Faass, Oliver
AU  - Faass O
FAU - Schlumpf, Margret
AU  - Schlumpf M
FAU - Lichtensteiger, Walter
AU  - Lichtensteiger W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060118
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Halogenated Diphenyl Ethers)
RN  - 0 (Phenyl Ethers)
RN  - 0 (Polybrominated Biphenyls)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Progesterone)
RN  - 11097-69-1 (Chlorodiphenyl (54% Chlorine))
RN  - 4TI98Z838E (Estradiol)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 7REL09ZX35 (pentabromodiphenyl ether)
SB  - IM
MH  - Adipose Tissue/chemistry
MH  - Animals
MH  - Chlorodiphenyl (54% Chlorine)/*toxicity
MH  - Estradiol/pharmacology
MH  - Estrogen Receptor alpha/genetics/metabolism
MH  - Estrogen Receptor beta/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Halogenated Diphenyl Ethers
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Ovariectomy
MH  - Phenyl Ethers/blood/pharmacokinetics/*toxicity
MH  - Polybrominated Biphenyls/blood/pharmacokinetics/*toxicity
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Receptors, Progesterone/genetics/metabolism
MH  - Uterus/*drug effects/metabolism
EDAT- 2006/01/18 09:00
MHDA- 2006/04/08 09:00
CRDT- 2006/01/18 09:00
PHST- 2005/09/10 00:00 [received]
PHST- 2005/12/08 00:00 [revised]
PHST- 2005/12/09 00:00 [accepted]
PHST- 2006/01/18 09:00 [pubmed]
PHST- 2006/04/08 09:00 [medline]
PHST- 2006/01/18 09:00 [entrez]
AID - S0300-483X(05)00634-7 [pii]
AID - 10.1016/j.tox.2005.12.004 [doi]
PST - ppublish
SO  - Toxicology. 2006 Mar 15;220(2-3):104-16. doi: 10.1016/j.tox.2005.12.004. Epub 
      2006 Jan 18.