title: Effect of maternal immunopotentiation on apoptosis-associated molecules expression in teratogen-treated embryos.
abstract: OBJECTIVE
  Potentiation of the maternal immune system was shown by us to affect the embryonic response to teratogenic insults. In order to understand better the mechanisms underlying that phenomenon, we explored the effect of maternal immunopotentiation by rat splenocytes on the early stages of the embryonic response to cyclophosphamide (CP).
  
  
  METHODS
  Immunopotentiated CP-treated embryos were analysed for cell cycle changes by flow cytometry, while cell proliferation and apoptosis were assessed by 5'-bromo-2'-deoxyuridine (BrdU) incorporation and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) respectively. The expression of the p65 subunit of NF-kappaB, IkappaBalpha, Bax, bcl-2 and p53 was assessed by flow cytometry.
  
  
  RESULTS
  Exposure to CP resulted in significant growth retardation and in the appearance of cellular damage, a reduction in cell proliferation and the appearance of apoptotic cells, which were all found to be delayed in immunopotentiated embryos. In parallel, CP-treated embryos demonstrated a reduction in the percentage of p65- or IkappaBalpha-positive cells, while the percentage of bcl-2- or p53-positive cells increased initially and decreased later. Those changes were normalized by maternal immunopotentiation when tested at 24 hrs after exposure to the teratogen.
  
  
  CONCLUSIONS
  Our data implicate maternal immunopotentiation to protect the embryo against teratogenic insults, possibly through its effect on the expression of p65, bcl-2 or p53.
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel. shoshans@post.tau.ac.il
authors.forename: Shoshana
authors.initials: S
authors.lastname: Savion
authors.forename: Ilan
authors.initials: I
authors.lastname: Aroch
authors.forename: Keren
authors.initials: K
authors.lastname: Mammon
authors.forename: Hasida
authors.initials: H
authors.lastname: Orenstein
authors.forename: Amos
authors.initials: A
authors.lastname: Fein
authors.forename: Arkady
authors.initials: A
authors.lastname: Torchinsky
authors.forename: Vladimir
authors.initials: V
authors.lastname: Toder
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004622:Embryo, Mammalian / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005317:Fetal Growth Retardation / Q000276:immunology*; D020672:I-kappa B Proteins / Q000096:biosynthesis; D007114:Immunization; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D009153:Mutagens / Q000009:adverse effects; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D019892:eIF-2 Kinase / Q000096:biosynthesis
chemical_list: C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D009153:Mutagens; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D003520:Cyclophosphamide; D019892:eIF-2 Kinase