Effects of maternal ethanol consumption on hematopoietic cells in the rat fetal liver☆

Abstract 

During development, there are many factors to be considered in studying the efficacy of the hematopoietic system to provide the immune system with adequate numbers of functional cells within the immune repertoire. Hematopoietic cells must be able to develop, proliferate, and emigrate from the hematopoietic fetal liver to other tissues of the body, such as the thymus and bone marrow. There is evidence that ethanol consumption causes immune deficiencies in adults and that maternal ethanol consumption causes immune deficiencies in children, both with correlative effects on cells and cytokinetic regulators. Therefore, the ability of the hematopoietic system to seed the immune system may be jeopardized by maternal ethanol consumption. In this study, test groups included female rats (1) fed a Lieber–DeCarli ethanol liquid diet, (2) pair-fed a control liquid diet, or (3) fed standard laboratory chow. Livers were removed from fetuses 18 and 21 days postconception (dpc) and analyzed by immunophenotyping and flow cytometry. There was a 22% and 38% decrease in fetal body weight and a 25% and 30% decrease in fetal liver weights between ethanol-fed and pair-fed groups at 18 and 21 dpc, respectively. At 18 dpc, fetal body and liver weights of the pair-fed animals were also significantly reduced to those of the chow-fed group. However, by 21 dpc, both body and liver weights of the two control groups were not statistically different. The effects of maternal ethanol consumption on the distribution of hematopoietic cells were characterized by using monoclonal antibodies (mAbs) anti-CD43 (a progenitor hematopoietic cell marker) versus labeling with anti-Vβ8.2 (pre-T cells), anti-B220 (pre-B cells), and anti-NKR-P1A (pre-natural killer cells). With the use of flow cytometric analysis, at 18 dpc ethanol-exposed fetuses showed 40% and 62% decreases in B220⁺ and Vβ8.2⁺ cells, respectively, versus findings for pair-fed controls, with no significant change in NKR-P1A⁺ cells. At 21 dpc, ethanol-exposed fetuses showed a 46% decrease in B220⁺ cells among the CD43⁺ cells, with a 50% increase in Vβ8.2⁺ cells. Observed alterations in gross fetal body and liver weights, together with modifications in the percentage of hematopoietic cells in the fetal liver after maternal ethanol consumption, strongly support the suggestion that the ability of the hematopoietic system to impart a repertoire of cells that are functional in the regulatory and effector mechanisms of the immune process may be compromised.

Keywords:  Ethanol, Immune development, Hematopoietic cells