title: Hepatotoxicity induced by neonatal exposure to diethylstilbestrol is maintained throughout adulthood via the nuclear receptor SHP.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: INSERM U 1103, Génétique Reproduction et Développement (GReD) , BP 80026, F-63171 Aubière Cedex , France +33 4 73407415 ; +33 4 73407042 ; david.volle@inserm.fr.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Vega
authors.forename: Marine
authors.initials: M
authors.lastname: Baptissart
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Martinot
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Saru
authors.forename: Silvère
authors.initials: S
authors.lastname: Baron
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: David H
authors.initials: DH
authors.lastname: Volle
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004054:Diethylstilbestrol / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000502:physiology; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency*
chemical_list: D004968:Estrogens, Non-Steroidal; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D004054:Diethylstilbestrol
keywords: estrogenic endocrine disrupter; liver; small heterodimer partner