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The effects of prenatal alcohol exposure on endochondral bone development in the fetal rat Snow, Mary Elizabeth

Abstract

Maternal ethanol intake during pregnancy results in impairments in general growth and skeletal development. However, it is unknown if ethanol’s effects on skeletal development result from generalized growth retardation or effects specific to bone. Additionally, the level of ethanol exposure required to produce skeletal effects is unknown. The objective of this thesis was to determine if prenatal ethanol exposure has specific effects on bone development, in addition to its effects on general growth, in the fetal [i.e. fœtal ] rat. The studies in this thesis were designed to test the hypotheses that (1) prenatal ethanol exposure affects skeletal development at doses of ethanol lower than those required to affect general growth (assessed by fetal body weight and length), (2) skeletal sites differ in their sensitivity to the effects of prenatal ethanol exposure and (3) prenatal ethanol exposure disrupts the morphology of the growth plate of the fetal tibia. The first study examined the effect of different doses of ethanol (designed to approximate low, moderate and high levels of exposure) on fetal growth and skeletal development. This study showed that endochondral ossification was affected by a moderate level of ethanol exposure, whereas body weight and length were only affected by a high level of exposure. Furthermore, the effects of ethanol varied by bone, with bones that undergo more development in utero being more sensitive than bones that are less developed in utero. Taken together, these data indicate the ethanol’s effects on endochondral ossification are independent of ethanol’s effects on general growth and that ethanol may affect the later, rather than the earlier, stages of endochondral ossification. The second study examined the effect of a high level of ethanol exposure on the histological stages of fetal bone development in the tibia, one of the bones found to be most affected by ethanol exposure. Ethanol exposure resulted in decreased tibial length, which was due to a decrease in the length of the diaphysis rather than the epiphyses. In addition, ethanol exposure resulted in a decrease in the resting zone length (which was proportional to the decrease in total bone length) and an enlargement of the hypertrophic zone length. As there is increasing evidence to suggest that the intrauterine environment may influence long-term bone health, the effects of prenatal ethanol exposure on fetal skeletal development could potentially increase the offspring’s risk of osteoporosis later in life.

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