Hematopoietic system are major contributors in fetal immune development. The liver is the primary site of hematopoiesis in the rodent fetus. Histologically, it has been established that liver cells of hematopoietic origin disappear within 2 weeks after birth. The life span of these cells is regulated by many factors critical in the viability and function of these cells. Apoptosis (programmed cell death) occurs during embryonic development as well as in maintenance of tissue homeostasis. The role of and importance of apoptosis for the development and function of lymphoid cells has been extensively investigated, however less clear is the role apoptosis plays in regulating early progenitor and stem cells of hematopoietic origin in the liver. Ethanol and its metabolites produce specific fetal alcohol syndrome (FAS)-related malformations, including cell death. There is evidence that ethanol consumption causes immunodeficiencies in adults and that maternal ethanol consumption causes immunodeficiencies in children, both with correlative effects on cells and cytokine regulators. Very limited data exists characterizing the effect of maternal ethanol consumption of fetal liver hematopoietic cells, cytokine regulators and adhesion molecules. It is hypothesized in this study that maternal alcohol consumption alters the normal hematopoietic process that occurs in fetal liver during gestation, and thus its ability to seed the immune system is impaired. We propose to study the female rat liver for apoptosis utilizing 7-amino-actinomycin D (7-AAD) with Annexin V- Phycoerythrin. Apoptotic gene expression will be done to evaluate the mRNA levels of significant molecules participating in the induction and suppression of apoptosis.
The Specific Aims of this project are: 1. To evaluate the effects of maternal alcohol consumption on normal hematopoietic cell development in the fetal liver. 2. To evaluate the effects of maternal alcohol consumption on specific cytokine, growth factor and/or adhesion molecule expression patterns in hematopoietic or stromal cells in the fetal liver. 3. To evaluate the effect of maternal alcohol consumption on the rate of apoptosis of hematopoietic cells.
