title: Sex specific changes in placental growth and MAPK following short term maternal dexamethasone exposure in the mouse.
abstract: OBJECTIVE
  Maternal glucocorticoid (GC) exposure during pregnancy can alter fetal development and program the onset of disease in adult offspring. The placenta helps protect the fetus from excess GC exposure but is itself susceptible to maternal insults and may be involved in sex dependant regulation of fetal programming. This study aimed to investigate the effects of maternal GC exposure on the developing placenta.
  
  
  METHODS
  Pregnant mice were treated with dexamethasone (DEX-1 μg/kg/h) or saline (SAL) for 60 h via minipump beginning at E12.5. Placentas were collected at E14.5 and E17.5 and the expression of growth factors and placental transporters examined by real-time PCR and/or Western blot. Histological analysis was performed to assess for morphological changes.
  
  
  RESULTS
  At E14.5, DEX exposed male and female fetuses had a lower weight compared to SAL animals but placental weight was lower in females only. Hsd11b2 and Vegfa gene expression was increased and MAPK1 protein expression decreased in the placentas of females only. At E17.5 placental and fetal body weights were similar and differences in MAPK were no longer present although HSD11B2 protein was elevated in placentas of DEX females. Levels of glucose or amino acid transporters were unaffected.
  
  
  CONCLUSIONS
  Results suggest sex specific responses to maternal GCs within the placenta. Decreased levels of MAPK protein in placentas of female fetuses suggest alterations in the MAPK pathway may contribute to the lower placental weights in this sex. This may contribute towards sex specific fetal programming of adult disease.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, 4072, Australia.
authors.forename: J S M
authors.initials: JS
authors.lastname: Cuffe
authors.forename: H
authors.initials: H
authors.lastname: Dickinson
authors.forename: D G
authors.initials: DG
authors.lastname: Simmons
authors.forename: K M
authors.initials: KM
authors.lastname: Moritz
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis*; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects* / Q000473:pathology; D010929:Placentation; D011247:Pregnancy; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D012737:Sex Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D011965:Receptors, Glucocorticoid; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D003907:Dexamethasone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1