PMID- 25263461
OWN - NLM
STAT- MEDLINE
DCOM- 20150720
LR  - 20141114
IS  - 1744-7631 (Electronic)
IS  - 1472-8222 (Linking)
VI  - 18
IP  - 12
DP  - 2014 Dec
TI  - Hepatotoxicity induced by neonatal exposure to diethylstilbestrol is maintained 
      throughout adulthood via the nuclear receptor SHP.
PG  - 1367-76
LID - 10.1517/14728222.2014.964209 [doi]
AB  - BACKGROUND: Liver physiology is sensitive to estrogens, which suggests that the 
      liver might be a target of estrogenic endocrine disrupters (EED). However, the 
      long-term consequences of neonatal exposure to EED on liver physiology have 
      rarely been studied. The nuclear receptor small heterodimer partner (SHP) 
      mediates the deleterious effects of neonatal exposure to diethylstilbestrol (DES) 
      on male fertility. OBJECTIVES: As SHP is involved in liver homeostasis, we aimed 
      to determine whether neonatal estrogenic exposure also affected adult liver 
      physiology through SHP. Male mouse pups were exposed to DES in the first 5 days 
      of life. RESULTS: DES exposure leads to alterations in the postnatal bile acid 
      (BA) synthesis pathway. Neonatal DES-exposure affected adult liver BA metabolism 
      and subsequently triglyceride (TG) homeostasis. The wild-type males neonatally 
      exposed to DES exhibited increased liver weight and altered liver histology in 
      the adult age. The use of deficient male mice revealed that SHP mediates the 
      deleterious effects of DES treatment. These long-term effects of DES were 
      associated with differently timed alterations in the expression of epigenetic 
      factors. CONCLUSIONS: However, the molecular mechanisms by which neonatal 
      exposure persist to affect the adult liver physiology remain to be defined. In 
      conclusion, we demonstrate that neonatal DES exposure alters adult hepatic 
      physiology in an SHP-dependent manner.
FAU - Vega, Aurelie
AU  - Vega A
AD  - INSERM U 1103, Genetique Reproduction et Developpement (GReD) , BP 80026, F-63171 
      Aubiere Cedex , France +33 4 73407415 ; +33 4 73407042 ; david.volle@inserm.fr.
FAU - Baptissart, Marine
AU  - Baptissart M
FAU - Martinot, Emmanuelle
AU  - Martinot E
FAU - Saru, Jean-Paul
AU  - Saru JP
FAU - Baron, Silvere
AU  - Baron S
FAU - Schoonjans, Kristina
AU  - Schoonjans K
FAU - Volle, David H
AU  - Volle DH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140929
PL  - England
TA  - Expert Opin Ther Targets
JT  - Expert opinion on therapeutic targets
JID - 101127833
RN  - 0 (Estrogens, Non-Steroidal)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (nuclear receptor subfamily 0, group B, member 2)
RN  - 731DCA35BT (Diethylstilbestrol)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Animals, Newborn
MH  - Diethylstilbestrol/*toxicity
MH  - Epigenesis, Genetic/drug effects/physiology
MH  - Estrogens, Non-Steroidal/*toxicity
MH  - Liver/*drug effects/pathology/*physiology
MH  - Male
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, Cytoplasmic and Nuclear/*deficiency
OTO - NOTNLM
OT  - estrogenic endocrine disrupter
OT  - liver
OT  - small heterodimer partner
EDAT- 2014/09/30 06:00
MHDA- 2015/07/21 06:00
CRDT- 2014/09/30 06:00
PHST- 2014/09/30 06:00 [entrez]
PHST- 2014/09/30 06:00 [pubmed]
PHST- 2015/07/21 06:00 [medline]
AID - 10.1517/14728222.2014.964209 [doi]
PST - ppublish
SO  - Expert Opin Ther Targets. 2014 Dec;18(12):1367-76. doi: 
      10.1517/14728222.2014.964209. Epub 2014 Sep 29.