Reduced Birth Defects Caused by Maternal Immune Stimulation in Diabetic ICR Mice: Lack of Correlation with Placental Gene Expression

Abstract

Diabetes mellitus alters placental structure and function, events that may be related to embryopathy. Three different methods of maternal immune stimulation that modulate placental function and that result in approximately equal reduction of diabetic embryopathy were studied: footpad injection with complete Freund's adjuvant, intraperitoneal injection with granulocyte-macrophage colony stimulating factor (GM-CSF), or intraperitoneal injection with interferon-gamma (IFN-γ). A gene microarray was then used to examine expression of 151 placental genes. We hypothesized that maternal immune stimulation may overcome an embryopathy-inducing effect of diabetes on placenta, that might be detected by a shared profile of placental gene expression changes induced by the different immune stimulation procedures. However, the immune stimulation that caused the greatest reduction in birth defect incidence, IFN-γ, did not change the placental gene expression profile ascompared to control or diabetes. Complete Freund's adjuvant and GM-CSF significantly changed placental gene expression relative to control or diabetes, but differentially affected such genes. No common pattern of improved cytokine, cell-cycle, apoptotic, transcription factor, or other gene expression was identified, that might explain the ability of this procedure to reduce birth defects. These data suggest that maternal immune stimulation reduces birth defects in diabetic mice by a mechanism independent of placenta.