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Effects of in utero alcohol exposure on B-cell development in the murine fetal liver
K L Biber1, K M Moscatello, D C Dempsey
1Department of Microbiology and Immunology and the Biomedical Research Institute, Louisiana State University Medical Center, Shreveport 71130, USA.
Insights
In utero alcohol exposure impacts fetal B-cell development late in gestation. Alcohol-exposed mice show decreased mature B cells by day 18, leading to immune dysfunction at birth.
Area of Science:
- Immunology
- Developmental Biology
- Toxicology
Background:
- Fetal alcohol syndrome (FAS) is a leading cause of birth defects and developmental disabilities.
- In utero alcohol exposure causes growth retardation, mental retardation, physical abnormalities, and immune dysfunction.
- Previous studies showed delayed B lymphopoiesis in weaned mice exposed to alcohol in utero.
Purpose of the Study:
- To investigate the effects of in utero alcohol exposure on fetal B-cell development.
- To determine if alcohol exposure impacts B lymphopoiesis during fetal development, specifically in the fetal liver.
- To identify the gestational timing of alcohol's effects on B-cell development.
Main Methods:
- Utilized a mouse model for in utero alcohol exposure.
- Employed flow cytometry to analyze B-cell developmental intermediates in fetal livers.
- Compared B-cell populations between alcohol-exposed and control groups at various gestational ages.
Main Results:
- B-cell development proceeded normally until gestational day 17 in alcohol-exposed fetuses.
- Between days 17 and 18 of gestation, a significant disruption in B-cell population dynamics was observed.
- By gestational day 18, alcohol-exposed mice showed decreased numbers of mature B-cell progenitors and B cells.
Conclusions:
- In utero alcohol exposure significantly disrupts fetal B-cell development late in gestation.
- Alcohol exposure impairs the progression of B-lineage cells along the developmental pathway.
- This disruption leads to an immunocompromised state at birth in offspring exposed to alcohol in utero.
Abstract:
Fetal alcohol syndrome is one of the leading causes of birth defects in this country. Children exposed to alcohol in utero suffer from growth and mental retardation, physical abnormalities, and immune dysfunction. Previous work from this laboratory demonstrated that B lymphopoiesis is delayed in mice exposed to alcohol in utero. The deficit in B-cell development was apparent shortly after birth and extended to well after weaning. Because lymphopoiesis begins in the fetal liver, the current study was done to determine if fetal B-cell development was affected as well by in utero exposure to alcohol. We now show that the effects of in utero alcohol exposure on B lymphopoiesis do not become apparent until late in gestation. Flow cytometry was used to enumerate several intermediates in the B-cell developmental pathway. These phenotypic analyses showed that before day 17 of gestation, B-lineage intermediates developed normally when compared with control animals. However, between days 17 and 18 of gestation, an abnormality in the population dynamics of B-lineage intermediates became apparent in the fetal liver of alcohol-exposed mice. Early intermediates in the B-cell developmental pathway were present in normal numbers; however, the more mature progenitors as well as B cells were decreased in number by gestational day 18. These data suggest that in utero alcohol exposure disrupts the ability of B-lineage intermediates to progress along the developmental pathway to maturity, thereby leaving the animal immunocompromised at birth.