title: Prebreeding maternal immunostimulation with Freund's complete adjuvant reduces placental damage and distal limb defects caused by methylnitrosourea.
abstract: OBJECTIVE
  Immunostimulation reduces murine teratogen-induced birth defects. It is unclear if placental improvement contributes to this outcome. The current study examined murine placental ultrastructure and fetal limb development following maternal methylnitrosourea (MNU) exposure, +/-Freund's complete adjuvant (FCA) immunostimulation.
  
  
  METHODS
  Two murine strains (CD-1, C57BL/6N) were administered MNU on gestation day 9 (GD9), FCA pre-breeding, or FCA + MNU. Fetal limb and placental development were examined on GD14.
  
  
  RESULTS
  MNU decreased placental weight and reduced placental cellular viability; FCA reversed these effects. MNU shortened fetal limbs and increased digital defects in both strains. Placentas were less damaged in C57BL/6N versus CD-1 mice, and distal limb malformations improved only in CD-1 mice. FCA immunostimulation also increased pregnancy rate.
  
  
  CONCLUSIONS
  Improved fetal outcome from immune-stimulated mice may not be dependent on improved placental morphology. However, placental function and morphology in immune-stimulated mice may not directly correlate, thus functional improvements should be examined for possible relationship to reduced birth defects.
authors.affiliation: Department of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Blacksburg, VA 24060, USA. mrprater@vt.edu
authors.forename: Mary
authors.initials: M
authors.lastname: Renee Prater
authors.forename: Kurt L
authors.initials: KL
authors.lastname: Zimmerman
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Laudermilch
authors.forename: Steven D
authors.initials: SD
authors.lastname: Holladay
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005620:Freund's Adjuvant / Q000627:therapeutic use*; D017880:Limb Deformities, Congenital / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008431:Maternal-Fetal Exchange; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate
chemical_list: D008770:Methylnitrosourea; D005620:Freund's Adjuvant