Project
Effect of Prenatal Alcohol Exposure on Endochondral Bone Development
Principal Investigator(s): Kathy Keiver, phone: 604-822-0421, email: keiver@interchange.ubc.ca
Publications: This work will be presented as a poster at RSA, 2005 and as an oral presentation at the 2005 meeting of the Fetal Alcohol Syndrome Study Group.
Start/End Date: 2003-2005
Location: Food, Nutrition and Health, Faculty of Agricultural Sciences, UBC, Vancouver ,BC
Brief Description: Prenatal ethanol exposure retards growth and delays skeletal development. We have shown that ethanol’s effects on the skeleton occur even in the absence of general growth retardation, indicating that ethanol has specific effects on developing bone. Moreover, different bones vary in their sensitivity to ethanol, with greater effects occurring in those bones that undergo a greater proportion of their development in utero. This suggests that ethanol may specifically disrupt the later (rather than early) stages of bone formation.
The purpose of this study was to test this hypothesis by examining the effects of prenatal ethanol exposure on the different histological stages of bone formation. Female rats were fed a liquid diet with 36% ethanol-derived calories (ethanol, E group), or without ethanol (pair-fed, PF, or control, C groups) for 6 weeks; 3 weeks before breeding and during 3 weeks of pregnancy. E and C rats had ad lib access to diet, while PF rats were fed the same amount of diet as their E partners. Rats were terminated on d21 gestation and fetal tibiae fixed, decalcified, stained and sectioned for histological examination.
Photographs were taken at uniform magnification under light microscopy, and measurements made of the total bone length and the height of the resting, proliferative and hypertrophic chondrocyte zones. Maternal ethanol intake significantly decreased the total length of the tibia (vs. PF and C fetuses) and the height of the resting zone (vs. PF fetuses), and increased the height of the hypertrophic zone (vs. PF fetuses). Ethanol had no effect on the height of the proliferative zone. When expressed relative to total bone length, only the ethanol-induced increase in the height of the hypertrophic zone remained significant (vs. PF and C fetuses).
These results indicate that ethanol delays the exit of chondrocytes from the hypertrophic stage, consistent with our hypothesis that ethanol affects the later stages of bone formation, and suggests that ethanol may interfere with the initiation of cartilage calcification, chondrocyte apoptosis, or angiogenesis. Effects of ethanol on skeletal development could have important implications for long-term health, as they may increase the offspring’s risk of osteoporosis later in life.
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