title: Impairment of rat fetal beta-cell development by maternal exposure to dexamethasone during different time-windows.
abstract: OBJECTIVE
  Glucocorticoids (GCs) take part in the direct control of cell lineage during the late phase of pancreas development when endocrine and exocrine cell differentiation occurs. However, other tissues such as the vasculature exert a critical role before that phase. This study aims to investigate the consequences of overexposure to exogenous glucocorticoids during different time-windows of gestation for the development of the fetal endocrine pancreas.
  
  
  METHODS
  Pregnant Wistar rats received dexamethasone acetate in their drinking water (1 µg/ml) during the last week or throughout gestation. Fetuses and their pancreases were analyzed at day 15 and 21 of gestation. Morphometrical analysis was performed on pancreatic sections after immunohistochemistry techniques and insulin secretion was evaluated on fetal islets collected in vitro.
  
  
  RESULTS
  Dexamethasone given the last week or throughout gestation reduced the beta-cell mass in 21-day-old fetuses by respectively 18% or 62%. This was accompanied by a defect in insulin secretion. The alpha-cell mass was reduced similarly. Neither islet vascularization nor beta-cell proliferation was affected when dexamethasone was administered during the last week, which was however the case when given throughout gestation. When given from the beginning of gestation, dexamethasone reduced the number of cells expressing the early marker of endocrine lineage neurogenin-3 when analyzed at 15 days of fetal age.
  
  
  CONCLUSIONS
  GCs reduce the beta- and alpha-cell mass by different mechanisms according to the stage of development during which the treatment was applied. In fetuses exposed to glucocorticoids the last week of gestation only, beta-cell mass is reduced due to impairment of beta-cell commitment, whereas in fetuses exposed throughout gestation, islet vascularization and lower beta-cell proliferation are involved as well, amplifying the reduction of the endocrine mass.
authors: Laboratoire de Biologie Cellulaire, Université catholique de Louvain, Institut des Sciences de la Vie, Louvain-la-Neuve, Belgium.
authors: Olivier
authors: O
authors: Dumortier
authors: Nicolas
authors: N
authors: Theys
authors: Marie-Thérèse
authors: MT
authors: Ahn
authors: Claude
authors: C
authors: Remacle
authors: Brigitte
authors: B
authors: Reusens
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005333:Fetus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D018811:Maternal Exposure; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D001973:Bromodeoxyuridine; D003907:Dexamethasone; D007328:Insulin; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C498696:Neurog3 protein, rat