title: Impaired trophoblast invasion and increased numbers of immune cells at day 18 of pregnancy in the mesometrial triangle of type 1 diabetic rats.
abstract: BACKGROUND
  Type 1 diabetes (T1D) is associated with adverse pregnancy outcome, usually attributed to hyperglycemia. Recently, we showed that pregnancy outcome in normoglycemic T1D rats was characterized by decreased fetal and placental weight, suggesting impaired placental development. In the present study, we tested the hypothesis that trophoblast invasion and spiral artery (SA) remodeling is impaired in T1D rats ant that this is associated with aberrant local presence of NK cells and macrophages in the mesometrial triangle (MT).
  
  
  METHODS
  Placentae with MT from pregnant biobreeding diabetes-prone (BBDP; T1D model) rats, control biobreeding diabetes-resistant (BBDR) and Wistar-rats were dissected at day 18 of gestation and stained for trophoblast invasion, SA remodeling, uNK cells and macrophages.
  
  
  RESULTS
  Interstitial trophoblast invasion and SA remodeling was impaired in BBDP-rats vs. control rats, coinciding with increased presence of NK cells and an increased iNOS+/CD206+ ratio of macrophages.
  
  
  CONCLUSIONS
  Decreased fetal and placental weight in BBDP-rats was associated with diminished interstitial trophoblast invasion and less optimal SA remodeling, increased numbers of NK cells and increased iNOS+/CD206+ macrophage ratio in the MT of BBDP-rats.
  
  
  CONCLUSIONS
  The impaired trophoblast invasion and SA remodeling may be due to an aberrant local immune-response and may result in damage to the fetal placenta and insufficient supply of nutrients towards the fetus with eventually decreased fetal weight as a consequence.
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center, Groningen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Groen
authors.affiliation: Department of Pathology and Medical Biology, Div. of Medical Biology, University of Groningen, University Medical Center, Groningen, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: Uuldriks
authors.affiliation: Department of Pathology and Medical Biology, Div. of Medical Biology, University of Groningen, University Medical Center, Groningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: de Vos
authors.affiliation: Department of Cell Biology, Div. of Immunology, University of Groningen, University Medical Center, Groningen, The Netherlands.
authors.forename: J T
authors.initials: JT
authors.lastname: Visser
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center, Groningen, The Netherlands.
authors.forename: T P
authors.initials: TP
authors.lastname: Links
authors.affiliation: Department of Pathology and Medical Biology, Div. of Medical Biology, University of Groningen, University Medical Center, Groningen, The Netherlands. Electronic address: m.m.faas@umcg.nl.
authors.forename: M M
authors.initials: MM
authors.lastname: Faas
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology; D010064:Embryo Implantation / Q000276:immunology; D004717:Endometrium / Q000276:immunology* / Q000473:pathology; D005260:Female; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000276:immunology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014327:Trophoblasts / Q000502:physiology*
keywords: Biobreeding diabetes prone rats; Immune cells; Placenta; Spiral artery remodeling; Trophoblast invasion; Type 1 diabetes