Title page for ETD etd-01262007-141024

Type of Document Master's Thesis
Author Laudermilch, Chelsea Lee
URN etd-01262007-141024
Title Birth Defect Amelioration and Placental cytokine Expression in Mnu-Exposed Dams treated With Ifn-Gamma
Degree Master of Science
Department Biomedical and Veterinary Sciences
Advisory Committee
Advisor Name Title
Prater, Mary Renee Committee Chair
Holladay, Steven D. Committee Member
Huckle, William R. Committee Member
  • teratogenesis
  • IFN-gamma
  • cytokine
  • Birth defect
  • placenta
Date of Defense 2007-01-16
Availability unrestricted
Each year, 7.9 million babies are born with birth defects. Seventy percent of those could be prevented, ameliorated, or repaired; yet 3.2 million children still die by the age of three (March of Dimes Global Report 2006). We have found that non-specific maternal immune stimulation with the cytokine interferon-gamma (IFN-gamma) can successfully ameliorate some of these defects in the C57BL/6N mouse model. We have observed a reduction in the distal limb malformations syndactyly, polydactyly, and webbing by 47%, 100%, and 63% respectively when IFN-gamma is given 2 days prior to MNU administration. We have also observed that IFN-gamma works at the placental level to protect against MNU-induced damage. Trophoblast loss and associated cytokine alterations occur in gestation day (GD) 14 placenta following GD9 MNU exposure, showing that fetal-maternal communication can be hindered due to MNU. In the labyrinthine layer of the placenta, we observed multifocal fibrinous necrosis of endothelial cells due to MNU, however IFN-gamma almost completely protected the trophoblast and endothelial cells when given to the dam as an immune stimulant. To determine the genes participating in these processes, gene microarray studies were conducted. Hepatocyte growth factor (HGF), interleukin 1 beta (IL1Β), and insulin-like growth factor 2 (IGF2) were elucidated as genes that were significantly expressed in GD12 placenta. These genes are similar in that they are all connected to the Jak-Stat signaling pathway. These findings provide a possible mechanism for birth defect reduction by maternal immune stimulation with IFN-gamma in MNU-challenged mice.
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