Prenatal alcohol exposure reduces mandibular calcium and phosphorus concentrations in newborn rats (original) (raw)
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Effect of Duration of Maternal Alcohol Consumption on Calcium Metabolism and Bone in the Fetal Rat
Alcoholism: Clinical & Experimental Research, 2004
Background: Prenatal ethanol exposure can retard fetal growth and delay skeletal development. Ethanol also impairs maternal calcium (Ca) homeostasis and this impairment could mediate some of ethanol's effects on the fetal skeleton. Our previous studies suggest that the duration of maternal ethanol consumption may be an important factor for determining the severity of ethanol's effects on Ca homeostasis and fetal skeletal development. The purpose of this study was, therefore, to determine the effect of the duration of maternal ethanol consumption on fetal growth and skeletal development and to investigate the possibility that ethanol's effects may be related to perturbations in fetal/maternal Ca homeostasis. Methods: Rats were fed ethanol (36% ethanol-derived calories) in liquid diets for 3 weeks (days 1-21 of gestation) or 6 weeks (for 3 weeks before and throughout gestation). Fetuses were collected on day 21 of gestation, and body weight and length were measured. Fetuses were stained to determine the degree of skeletal ossification, and fetal blood was analyzed for ethanol, Ca (total and ionic Ca), albumin, parathyroid hormone (PTH), and osteocalcin. Results: Maternal ethanol consumption decreased fetal growth and delayed fetal skeletal development. Although there was a trend for fetal body length and serum osteocalcin levels to be more severely affected with an increased duration of maternal ethanol consumption, duration had no effect on fetal body weight or skeletal ossification. Fetal Ca homeostasis was also affected by ethanol exposure, with fetal hypocalcemia apparent after 6 weeks of maternal ethanol intake. A significant inverse relationship was found between fetal blood Ca levels and blood alcohol concentration (BAC), suggesting that the severity of the fetal hypocalcemia may have been related to differences in fetal BAC, rather than duration of maternal ethanol intake. Fetal serum PTH levels did not differ significantly among treatment groups indicating that the fetal hypocalcemia was not caused by a decrease in PTH levels. Conclusions: Prenatal ethanol exposure impaired Ca homeostasis and skeletal development in the fetal rat. The severity of ethanol's effects was only marginally dependent on the duration of maternal ethanol consumption per se and seemed to be more related to the relative exposure of the fetus to ethanol (fetal BAC). The relationship between the ethanol-induced fetal hypocalcemia and skeletal effects remains to be determined.
Effect of Duration of Alcohol Consumption on Calcium and Bone Metabolism During Pregnancy in the Rat
Alcoholism: Clinical & Experimental Research, 2003
Background: Little is known about the consequences of drinking during pregnancy for the long-term health of the mother. Alcohol (ethanol) has been shown to disrupt calcium (Ca) homeostasis and is known to have deleterious effects on bone. During pregnancy, bone turnover is increased to maintain Ca homeostasis; therefore, pregnancy may be a time of life when maternal bone is particularly susceptible to the effects of ethanol. This study investigated the effect of duration of ethanol consumption on Ca homeostasis and bone during pregnancy in the rat. Methods: Rats were fed ethanol (36% ethanol-derived calories) in liquid diets for 3 (21 days gestation only) or 6 (3 weeks before and throughout 21 days gestation) weeks. Maternal blood was analyzed for Ca (total and ionized Ca [iCa]), the Ca-regulating hormones (parathyroid hormone [PTH], 1,25(OH) 2 D, calcitonin), and osteocalcin (a marker for bone formation). Bone was analyzed for ash (mineral) content. Results: Dams consuming ethanol (E dams) had decreased blood Ca levels (total and iCa) at both 3 and 6 weeks, but iCa was lower in E dams after 6 compared with 3 weeks. Importantly, ethanol seemed to interfere with the normal compensatory response to these decreased Ca levels. In contrast to pair-fed controls, serum PTH levels actually were decreased, 1,25(OH) 2 D levels failed to increase, and calcitonin levels were increased in ethanol-consuming dams, regardless of duration. Moreover, ethanol decreased bone formation, as indicated by serum osteocalcin levels, after both 3 and 6 weeks consumption, and after 6 weeks, the ash content of bone also was decreased. In addition, a relationship was found between the blood alcohol concentration (BAC) and some measures of Ca and bone metabolism. Serum 1,25(OH) 2 D and osteocalcin levels varied inversely, whereas serum calcitonin varied directly with BAC, suggesting that time of sampling after drinking may be an important variable for interpreting ethanol's effects on Ca and bone metabolism. In all rats, serum osteocalcin levels varied directly with PTH and 1,25(OH) 2 D levels. Conclusions: Ethanol consumption during pregnancy impaired Ca homeostasis in the dam, regardless of duration of consumption, and resulted in decreased bone formation and ash content of bone. Significant relationships among the Ca-regulating hormones, BAC, and osteocalcin support the hypothesis that ethanol's effects on the Ca-regulating hormones may mediate some of its effects on bone.
European Journal of General Medicine
Aim: To investigate the effects of alcohol contained continuous modified liquid diet ingestion in rats' offspring on bone length, bone mineral density and body weights. Methods: In Alcoholic group (n= 19), Wistar rats' offspring were provided 7.2% ethanol during intrauterine and postnatal breast feeding period (4 weeks). These rats were fed by modified liquid diet without ethanol till 12 weeks of age after weaning. Control group (pair-fed control rats, n= 9) was fed an isocaloric Modified Liquid Diet without ethanol throughout the experiment (12 weeks). In the all rats, bone mineral density (BMD) of the bilateral tibias were measured with dual-energy X-ray absorptiometry (DEXA) and statistically compared. Results: Compared with control group, there was a significant fall in tibia length (p=0.02); but the mild loss of body weight and bone mineral density was not found statistically significant (p>0.05). Conclusion: Mild decrease in bone loss and body weights in offspring rats of provided alcohol during intrauterine life may be attributed the irregular feeding habits due to social factors in chronic alcohol consumption in human. Our findings related the significant short tibia length in chronic alcohol treated rats during pregnancy and lactation period were found correlated with the studies in human and animal models.
Effect of Prenatal Ethanol Exposure on Fetal Calcium Metabolism
Alcoholism: Clinical and Experimental Research, 1997
Alcohol consumption has adverse effects on both adult and developing bone. The mechanisms by which alcohol affects bone, however, are unknown. This study examined the possibility that maternal alcohol consumption may affect fetal bone development by altering fetal levels of parathyroid hormone (PTH), 1,25(OH),D, or calcitonin (hormones that regulate calcium (Ca) and bone metabolism in the adult animal). Female Sprague-Dawley rats were bred and divided into three groups: 1 group was fed lab chow ad libitum (Control; C) and the other 2 groups received a liquid diet with (Ethanol; E) or without (Pair-fed; PF) ethanol. Blood from dams and fetuses was collected on day 21 of gestation, and selected fetuses were stained for determination of the degree of bone ossification. Mean fetal body weight and fetal skeletal ossification were reduced in the E compared with PF and C groups. Total Ca levels in fetal serum, however, showed a trend to be increased in E compared with PF and C fetuses, and no significant group dfirences were found in fetal serum levels of albumin, PTH, or calcitonin. Serum levels of 25-OH-D and 1,25(OH),D were significantly decreased in E and PF, compared with C fetuses. Total Ca levels in maternal serum did not vary with the group; however, serum albumin levels were higher in E, compared with PF and C dams, suggesting that serum ionic Ca levels may have been reduced in the E dams. Serum levels of 25-OH-D were reduced in the E, compared with PF and C dams, whereas levels of 1,25(0H),D were elevated. PTH levels did not vary among groups. Interestingly, serum calcitonin levels were elevated in the E, compared with PF and C, dams. These results indicate that the effects of ethanol on fetal bone development do not appear to be related to alterations in fetal serum levels of PTH, 1,25(OH),D, or calcitonin. Maternal ethanol consumption, however, results in reduced appetite and a decrease in dietary Ca intake. Despite the reduced Ca intake, the ability of the dam to maintain Ca homeostasis appeared intact, although this may be dependent on the duration of ethanol consumption.
Prenatal ethanol exposure disrupts the histological stages of fetal bone development
Bone, 2007
Maternal ethanol intake during pregnancy results in impairments in general growth and skeletal development in the offspring. We have previously shown that ethanol retards skeletal ossification at doses lower than those that affect growth. Moreover skeletal sites vary in their sensitivity to ethanol effects, with more severe effects occurring in bones that undergo a greater proportion of their development in utero. Taken together, these data suggest that ethanol has specific effects on bone development, and that later stages in the ossification process may be particularly affected. Such effects could have important implications for the offspring's long-term bone health, as studies suggest that the intrauterine environment can program the skeleton. The present study examined the histological stages of bone development to determine if prenatal ethanol exposure alters the morphological development of the growth plate in the fetal rat. Rats were fed a liquid diet containing ethanol (Ethanol, E group), or without ethanol (Pair-Fed, PF, or Control, C groups) for 6 weeks: 3 weeks prior to breeding and during 3 weeks of pregnancy. Fetal tibiae were fixed, decalcified and stained for histological analysis on day 21 of gestation. Maternal ethanol intake resulted in a significant decrease in fetal total bone and diaphysis lengths, compared with tibiae from PF and C fetuses. Although the lengths of the epiphyses were not affected, ethanol disrupted the organization of the histological zones within the epiphyses. Prenatal ethanol exposure decreased the length of the resting zone, but increased the length of the hypertrophic zone. Enlargement of the hypertrophic zone is consistent with an effect of ethanol on the later stages of bone development; however ethanol's effect on the resting zone indicate that earlier stages of bone development may also be disrupted. The functional significance of these morphological changes to long-term bone health remains to be determined.
OnLine Journal of Biological Sciences, 2015
Alcohol exerts teratogenic effects and its consumption during pregnancy may cause various alterations in the fetus, including deficit of bone development. The objective of this study was to evaluate the initial responses, on osteoblasts isolated from newborn rat calvaria, after prenatal ethanol exposure. Nine pregnant rats were divided into three groups according to the diet fed during pregnancy: Rats fed 20% ethanol, Pair-fed and control were the groups. At 3 days of life, newborn rats were euthanized for removal of the calvaria and isolation of osteogenic cells by sequential enzymatic digestion. The cells were cultured for a maximum period of 14 days. The effect of alcohol was investigated by the measurement of cell adhesion, proliferation and viability, total protein content, Alkaline Phosphatase (ALP) activity and bone matrix formation. The results showed the highest proliferation in ETH group on the 3 th day and the highest ALP activity and bone matrix formation, in this group, on the 14 th day, indicating that prenatal ethanol seems to affect the proliferation early and the ALP activity and bone matrix formation in more advanced periods.
Effect of prenatal alcohol exposure on bony craniofacial development: A mouse MicroCT study
Alcohol, 2013
Craniofacial bone dysmorphology is an important but under-explored potential diagnostic feature of fetal alcohol spectrum disorders. This study used longitudinal MicroCT 3D imaging to examine the effect of prenatal alcohol exposure on craniofacial bone growth in a mouse model. C57BL/6J dams were divided into 3 groups: alcohol 4.2% v/v in PMI Ò liquid diet (ALC), 2 weeks prior to and during pregnancy from embryonic (E) days 7-E16; pair-fed controls (PF), isocalorically matched to the ALC group; chow controls (CHOW), given ad libitum chow and water. The MicroCT scans were performed on pups on postnatal days 7 (P7) and P21. The volumes of the neurocranium (volume encased by the frontal, parietal, and occipital bones) and the viscerocranium (volume encased by the mandible and nasal bone), along with total skull bone volume, head size, and head circumference were evaluated using general linear models and discriminant analyses. The pups in the alcohol-treated group, when compared to the chow-fed controls (ALC vs CHOW) and the isocaloric-fed controls (ALC vs PF), showed differences in head size and circumference at P7 and P21, the total skull volume and parietal bone volume at P7, and volume of all the tested bones except nasal at P21. There was a growth trend of ALC < CHOW and ALC < PF. While covarying for gender and head size or circumference, the treatment affected the total skull and mandible at P7 (ALC > CHOW), and the total skull, parietal bone, and occipital bone at P21 (ALC < CHOW, ALC < PF). While covarying for the P7 measures, the treatment affected only the 3 neurocranial bones at P21 (ALC < CHOW, ALC < PF). Discriminant analysis sensitively selected between ALC and CHOW (AUC ¼ 0.967), between ALC and PF (AUC ¼ 0.995), and between PF and CHOW (AUC ¼ 0.805). These results supported our hypothesis that craniofacial bones might be a reliable and sensitive indicator for the diagnosis of prenatal alcohol exposure. Significantly, we found that the neurocranium (upper skull) was more sensitive to alcohol than the viscerocranium (face).
Effect of Maternal Ethanol Consumption on Maternal and Fetal Calcium Metabolism
Alcoholism: Clinical and Experimental Research, 1996
Alcohol consumption can have deleterious effects on both adult and developing bone. The mechanism(s) by which alcohol affects bone, however, is unknown. This study investigated the possibility that alcohol affects bone by alterations in calcium (Ca) metabolism. Female rats were fed lab chow ad libitum (C, Control) or a liquid diet with (E, Ethanol) or without (PF, Pair-Fed) ethanol. After 2 weeks on their respective diets, the rats were bred and the experimental diets continued throughout gestation. Blood (dams only) and tissue were collected on day 21 of gestation. The Ca content of maternal bone showed a trend toward a decrease in E and PF compared with C dams. Ionic Ca (iCa) levels were decreased in the blood of the E compared with PF and C dams. Serum parathyroid hormone levels were elevated in the E compared with C dams, consistent with the low iCa levels. Serum levels of 1 ,25(OH),D, however, were elevated only in the PF dams. Mean fetal body weight and fetal skeletal ossification were reduced in the E compared with PF and C groups, but no group differences were found in fetal Ca content. These results indicate that maternal ethanol consumption compromised the ability of the dam to regulate her blood iCa levels, possibly partly due to a failure to increase 1,25(OH),D levels. The delays in skeletal development observed in the ethanol exposed fetuses, however, do not appear to result from impaired placental Ca transfer.
Prenatal ethanol exposure has differential effects on fetal growth and skeletal ossification
Bone, 2005
There is increasing evidence suggesting that the intrauterine environment may influence long-term bone health and the risk of developing osteoporosis in later life. Alcohol (ethanol) is one factor whose presence in the prenatal environment has long-term consequences for the offspring, including permanent growth retardation. Moreover, prenatal ethanol exposure retards both fetal and postnatal bone development. It is unknown if ethanol's effects on skeletal development result from generalized growth retardation or effects specific to skeletal development. Furthermore, the level of ethanol exposure required to produce skeletal effects is unknown. The objectives of this study were to determine (1) if ethanol exerts specific effects on fetal skeletal development that are independent from its effects on general growth, and (2) the level of prenatal ethanol exposure required to affect fetal growth and skeletal ossification. Rats were fed isocaloric diets with ethanol (15%, 25%, or 36% ethanol-derived calories (EDC), approximating low, moderate, and high exposure levels), or without ethanol (pair-fed, PF, or control, C groups), prior to and throughout 21 days of gestation. The degree of Einduced delay in development was determined by comparison of E fetuses on d21 gestation to C fetuses on d17-d21 gestation. Prenatal ethanol exposure at 36% EDC decreased fetal body weight, length, and skeletal ossification compared with PF and C fetuses on d21 gestation. Importantly, effects on ossification, but not body weight or length, were also seen at the more moderate dose of 25% EDC, and the number of bones affected and the severity of effects on ossification tended to increase with dose of ethanol. Comparison of E fetuses on d21 gestation with C fetuses from d17 to 21 gestation indicated that the ethanol-induced delay in development differed for weight and skeletal ossification, and was not uniform among skeletal sites. Taken together, these data suggest that prenatal ethanol exposure has effects on fetal skeletal development that are independent of those on overall fetal growth, and that these effects occur even at moderate levels of maternal drinking. Effects of prenatal ethanol exposure on fetal skeletal development could potentially increase the offspring's risk of osteoporosis later in life.
Chronic Consumption of Alcohol Adversely Affects the Bone of Young Rats
Acta Ortopédica Brasileira
Objective: To assess the effect of chronic alcohol consumption on the longitudinal growth of the tibia and bone quality parameters in young rats under an experimental setup. METHODS: The control (n=10) rats received only water. The ethanol (n=10) rats received ethyl alcohol at concentrations established in the protocol for the induction of chronic alcohol consumption. The blood samples were immediately collected via cardiac puncture and processed to evaluate the levels of alkaline phosphatase by automated spectrophotometry. Following blood sample collection, both tibias were dissected, and weighed; the tibial length was measured., and the samples were stored in a freezer for future analysis of the bone mineral content and mechanical resistance, known as maximal load and stiffness. RESULTS: Compromised bone health, with a 35.3% decrease in the serum alkaline phosphatase levels (p < 0.01), a 10% decrease in the tibial mass (p < 0.05), and a 5.3% decrease in the tibial length (p ...