Developmental influence of magnesium deficiency on rat molar tooth composition and dental caries

The objective of this study was to determine if caries susceptibility of offspring could be altered by maternal magnesium deficiency. Magnesium deficiency was evident by reductions in the magnesium content of serum, tibia, milk, and muscle as well as by an increase in both serum and kidney calcium. Maternal magnesium deficiency however was not severe enough to influence gestational weight gain, litter size, pup survival or weanling pup weight. Offspring originating from these magnesium deficient dams had less calcium, phosphorus and zinc in molar dentin compared to controls at the end of a 45-day caries test period. This apparent preeruptive reduction in mineral content of offspring dentin was associated with higher caries scores on the first and second molar buccal surface.     

Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice

Maternal fructose consumption during pregnancy and lactation is associated with metabolic dysregulation in offspring. We tested the hypothesis that fish oil (FO) supplementation during pregnancy and lactation improves fructose-induced metabolic dysregulation in postpartum dams and offspring mice. We therefore aimed to determine the effects of FO supplementation on metabolic disruption in neonatal mice and dams induced by a maternal high-fructose diet (HFrD). The weight of the offspring of dams fed with HFrD on postnatal day 5 was significantly low, but this was reversed by adding FO to the maternal diet. Feeding dams with HFrD significantly increased plasma concentrations of triglycerides, uric acid, and total cholesterol, and decreased free fatty acid concentrations in offspring. Maternal supplementation with FO significantly suppressed HFrD-induced hypertriglyceridemia and hyperuricemia in the offspring. Maternal HFrD induced remarkable mRNA expression of the lipogenic genes Srebf1, Fasn, Acc1, Scd1, and Acly in the postpartum mouse liver without affecting hepatic and plasma lipid levels. Although expression levels of lipogenic genes were higher in the livers of postpartum dams than in those of nonmated mice, HFrD feeding increased the hepatic lipid accumulation in nonmated mice but not in postpartum dams. These findings suggest that although hepatic lipogenic activity is higher in postpartum dams than nonmated mice, the lipid consumption is enhanced in postpartum dams during pregnancy and lactation. Maternal FO supplementation obviously suppressed the expression of these lipogenic genes. These findings coincide with reduced plasma triglyceride concentrations in the offspring. Therefore, dietary FO apparently ameliorated maternal HFrD-induced dyslipidemia in offspring by suppressing maternal lipogenic gene expression and/or neonatal plasma levels of uric acid.     

Interaction between ethanol and low dietary zinc during gestation and lactation in the rat

Pregnant rats were fed individual liquid diets throughout gestation and lactation. The diets contained either 2 or 10 micrograms zinc/ml diet with or without 30% of the kilocalories supplied from ethanol. The low zinc diet produced a moderate zinc deficiency in dams evidenced by decreases in tissue zinc content, serum alkaline phosphatase activity and urinary zinc concentration. Despite the presence of high zinc content in the diet, ethanol antagonized the maternal zinc status to a level typical of that produced by the low zinc diet. The lowest zinc status, however, was found when low dietary zinc and ethanol were combined. The maternal interaction between ethanol and zinc also depressed offspring serum zinc and alkaline phosphatase activity in a similar manner. Ethanol, however, did not affect tissue content of calcium, magnesium or phosphorus, which indicates that ethanol is a specific antagonist of zinc utilization during gestation and lactation.     

High Dietary Fat Intake during Lactation Promotes the Development of Social Stress-Induced Obesity in the Offspring of Mice

This study examined how a maternal high-fat diet (HD) during lactation and exposure of offspring to isolation stress influence the susceptibility of offspring to the development of obesity. C57BL/6J mice were fed a commercial diet (CD) during pregnancy and a CD or HD during lactation. Male offspring were weaned at three weeks of age, fed a CD until seven weeks of age, and fed a CD or HD until 11 weeks of age. Offspring were housed alone (isolation stress) or at six per cage (ordinary circumstances). Thus, offspring were assigned to one of eight groups: dams fed a CD or HD during lactation and offspring fed a CD or HD and housed under ordinary circumstances or isolation stress. Serum corticosterone level was significantly elevated by isolation stress. High-fat feeding of offspring reduced their serum corticosterone level, which was significantly elevated by a maternal HD. A maternal HD and isolation stress had combined effects in elevating the serum corticosterone level. These findings suggest that a maternal HD during lactation enhances the stress sensitivity of offspring. White adipose tissue weights were significantly increased by a maternal HD and isolation stress and by their combination. In addition, significant adipocyte hypertrophy was induced by a maternal HD and isolation stress and exacerbated by their combination. Thus, a maternal HD and isolation stress promote visceral fat accumulation and adipocyte hypertrophy, accelerating the progression of obesity through their combined effects. The mechanism may involve enhanced fatty acid synthesis and lipid influx from blood into adipose tissue. These findings demonstrate that a maternal HD during lactation may increase the susceptibility of offspring to the development of stress-induced obesity.     

Low copper and brain abnormalities in fetus from triethylene tetramine dihydrochloride-treated pregnant mouse.

The effects of prenatal triethylene tetramine dihydrochloride (Trien-2HCl) exposure on fetal mice have been investigated on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 ppm as drinking water, ad libitum. At the level of 12,000 ppm, the frequency of total resorption tended to be high and that of fetal viability tended to be low, as compared to controls. Decreased maternal weight was observed in body, but not in liver, at the level of 12,000 ppm. Fetal body and cerebrum weights significantly decreased at the levels of 6,000 and 12,000 ppm; however, fetal liver weight remained unchanged. Maternal serum copper concentration was not affected by the Trien-2HCl. Fetal copper concentrations of liver and cerebrum were significantly lower in the Trien-2HCl-treated groups than in the controls, with levels decreasing in a dose-related manner. When the copper and zinc concentrations in the group treated at 12,000 ppm were compared with those in controls, significant decreases in both metals were observed in placenta but not in maternal liver. Changes in fetal zinc concentration varied by tissues: i.e., an increase in liver and no change in cerebrum. Fetal abnormalities were frequently observed in brain, and the frequency was increased with increasing levels of the Trien-2HCl. These results suggest that fetal brain abnormalities caused by Trien-2HCl may be due in part to induction of copper deficiency, which is almost equivalent to that in brindled mutant mouse.     

Evidence for increased selenium requirement for the rat during pregnancy and lactation

Adequacy of the National Research Council (NRC) selenium (Se) requirement for growth (0.1 ppm Se) was assessed in reproducing Sprague-Dawley rats. Either a casein-based diet with no added Se or the same diet supplemented with selenite to contain 0.05, 0.1, or 0.2 ppm Se was fed during pregnancy and lactation and to nonreproducing controls. Only 0.05 ppm Se was necessary to maintain maximal red blood cell (RBC) and liver Se concentrations and glutathione peroxidase (GSH-Px) activities in controls, whereas 0.2 ppm Se was necessary to maintain comparable RBC Se during pregnancy and tissue Se and GSH-Px activities during lactation. On d 2 of lactation, no differences in pup tissue Se or GSH-Px activities could consistently be related to maternal Se intake. By d 18 of lactation, however, Se status of nursing pups reflected maternal Se intake. Pups of dams fed 0.2 ppm Se had tissue Se and GSH-PX activities significantly greater than those of all other pups. Milk Se content correlated significantly with maternal Se intake and plasma Se and with pup tissue Se and GSH-Px activities. These results indicate that during reproduction 0.1 ppm Se is not adequate to maintain maternal tissue Se or GSH-Px activities comparable to those of normal controls; 0.2 ppm dietary Se is more appropriate, resulting in maternal GSH-PX activities similar to those of controls fed 0.1 ppm Se and milk Se concentrations that result in greater pup tissue GSH-Px activities.     

Effects of low levels of dietary lead and iron on hepatic RNA, protein, and minerals in young Japanese quail

Day-old Japanese quail were fed purified diets containing either 0.2 (control), 5.4, or 16.2 ppm lead as the acetate with either 25 (deficient) or 100 ppm (adequate control) iron for 2 weeks. Iron deficiency caused decreases in hemoglobin, iron, and manganese in the liver, and hepatic RNA synthesis. Iron deficiency also caused increased concentrations of lead, calcium, and molybdenum in the liver. Lead supplements caused increased concentrations of lead in the liver, and with adequate dietary iron, each supplemental lead level caused a slight decrease in the concentration of RNA in the liver. Treatment had no effect on DNA or protein synthesis, body weight, or liver weight in relation to body weight. These low levels of dietary lead did not cause the same adverse metabolic effects observed by others with higher levels of lead; however, iron deficiency increased lead uptake by the liver and affected RNA synthesis.     

Maternal protein restriction during pregnancy and lactation in rats imprints long-term reduction in hepatic lipid content selectively in the male offspring

Maternal protein restriction during pregnancy and lactation reduces whole body lipid stores and alters lipid homeostasis in the adult offspring. Lipid homeostasis in the body is regulated, in part, by the liver via the metabolic processes of synthesis and utilization of lipids. The present study tested the hypothesis that maternal protein restriction will imprint changes in hepatic lipid metabolism and thereby alter the hepatic lipid content of the adult offspring. Pregnant rats were fed purified diets containing 19% protein (control group) or 8% protein (low-protein group) throughout pregnancy and lactation. On day 28, pups from both groups were weaned onto regular laboratory chow. On days 65 and 150, male and female pups from each litter in both groups were killed and blood and liver collected. Maternal protein restriction was found to reduce birth weight and produce long-term reduction in the body weight of the offspring. On day 65, liver triglyceride content was decreased by 40% in the male offspring that were fed a low-protein diet. The reduction in liver triglyceride content persisted until day 150, at which time it was accompanied by decreases in hepatic cholesterol content. No such changes were observed in the female offspring. To determine if the alterations in liver lipid content resulted in compensatory changes in liver carbohydrate stores, hepatic glycogen content was measured in male offspring. Hepatic glycogen content was similar between the 2 groups on days 65 and 150. In conclusion, the present study in rats showed that maternal protein restriction during pregnancy and lactation imprints long-term changes in hepatic lipid content selectively in the male offspring.     

母体钙代谢与补钙对妊娠的影响

妊娠期缺钙严重影响母婴的安全健康 ,其原因是由于妊娠期母体钙代谢发生变化 ,使母体血清游离钙离子浓度降低 ,血清铅浓度增高。有关研究表明 ,母体缺钙导致血铅竞争性过高 ,使胎儿身长、体重均小于胎龄儿 ,胎儿宫内发育迟缓的发生率增高 ,甚至发生早产、死胎等。同时发现血清钙离子可能对内源性一氧化氮合成释放起调节作用 ,而内皮素是最强的缩血管物质之一 ,母体补钙可调节一氧化氮与内皮素的平衡 ,从而降低妊高征的发生率。因此孕期补充钙剂是非常重要的。     

Growth and development in rats and deficiency of magnesium and pyridoxine

Eight-eight female weanling Sprague-Dawley rats were fed diets containing either 650 or 150 mg magnesium/kg diet and 7.0 or 3.5 mg pyridoxine-HCl/kg diet, in a 2 x 2 factorial arrangement, during growth, gestation, and lactation. The objective of the study was to determine whether concurrent dietary deficiencies of magnesium and pyridoxine were synergistic, additive, or antagonistic with regards to effects on reproductive performance, growth, and development of offspring, and tissue content of magnesium and calcium. Body weight of dams and pups was not different between groups until day 9 of lactation, at which point those animals in either low magnesium group weighed less than the other. Litter size and birth weight were not different. Development, as measured by timing of unfolding of the external ear, opening of both eyes, and clinical emergence of incisors, was delayed in pups from litters in the low magnesium groups. A synergistic effect on delay of onset of ear unfolding by deficiency of both magnesium and pyridoxine was observed. Calcium content of heart and kidney from dams was increased in the low magnesium groups. Renal calcium was not further increased by the level of pyridoxine deficiency in this study. The calcium to magnesium ratio in heart from pups was higher in those from litters in the low magnesium and pyridoxine group than in the others. Results indicate that simultaneous deficiencies of magnesium and pyridoxine may impair function synergistically. Because these two nutrients are often reported to be presented in inadequate amounts in diets of women in their reproductive years, the potential exists for impaired reproductive success.     

Influence of different levels of dietary pyridoxine on milk composition in the rat

The effects of five different levels of dietary pyridoxine on milk composition were studied in the rat. Sprague-Dawley strain rats received diets containing 1.2, 2.4, 4.8, 9.6 or 19.2 mg pyridoxine-HCl/kg diet throughout growth, gestation and lactation. Milk samples obtained on days 10, 11, and 12 of lactation were similar in concentrations of total fat, solids-not-fat, carbohydrate, casein and non-casein protein for rats fed the five levels of pyridoxine. The level of vitamin B-6 in milk was significantly higher for rats fed 9.6 or 19.2 mg pyridoxine.HCl/kg diet compared to values for rats fed the three lower levels of vitamin. A higher level of dietary pyridoxine (9.6 mg/kg diet) was required to increase the levels of the vitamin in mammary gland and milk than was needed for maternal liver (4.8 mg/kg) or muscle tissue (2.4 mg/kg). The findings indicated that as the level of pyridoxine was decreased in the diet from an apparently adequate level, the concentration of the vitamin in milk decreased before that in liver or muscle tissue. This suggested that the concentration of the vitamin in milk was an indicator of marginal deficiency of vitamin B-6.     

哺乳期农村乳母乳汁无机元素含量的变化

目的了解哺乳期人乳无机元素含量的变化及其与乳母膳食的关联。方法采用横断面调查方法,收集55名陕西省澄城县农村健康乳母清晨乳样,利用原子吸收分光光度法测定乳汁钙、镁、铁、锰、锌和铜的浓度。采用24小时回顾法进行连续3天膳食调查,计算膳食营养素的摄入量。结果农村乳母乳汁中镁、锌、铜浓度随哺乳期延长明显降低,铁浓度随哺乳期延长而上升。乳母膳食钙摄入量约为钙膳食参考摄入量(DRI)1/3,膳食无机元素的摄入量与人乳相应元素之间无明显相关性。多因素分析表明,乳汁中钙与镁、铁与铜、锰与锌均呈正相关,钙分别与乳脂、铁、锌呈负相关。结论随哺乳期时间延长,成熟乳中镁、锌、铜浓度降低而铁浓度增加,乳母膳食钙的摄入严重不足,乳汁各元素与膳食相应元素之间无关联。     

Influence of dietary zinc on lead toxicity during gestation and lactation in the female rat.

Confirmed pregnant female albino rats received a purified diet containing either 12 or 120 ppm zinc with or without lead (0 to 500 ppm) from day 0 gestation through day 16 of lactation. An 11% reduction in dam weight gain during gestation and a 12% reduction in average pup weight in rats fed the low zinc plus lead diet was markedly different compared to controls not receiving lead and lead supplemented rats receiving supplemental zinc. Milk lead concentration was reduced in rats receiving additional dietary zinc and lead which was reflected in a 15% reduction in pup tibia lead concentration, a 20% reduction in inhibition of pup liver delta-aminolevulinic acid dehydratase activity and a 31% reduction in pup blood porphyrin concentration. Some of the beneficial effects of supplemental zinc on lead toxicity of pups may be explained by a reduction of both liver lead (40%) and blood lead (32%) concentration of dams. However an interaction between lead and zinc at the placental and mammary barriers must also be considered. The results of this study suggest that nutritional status of zinc may be an important factor in modifying lead burden of infants borne by women occupationally and environmentally exposed to lead.     

Zinc-vitamin A interaction in pregnant and fetal rats: supplemental vitamin A does not prevent zinc-deficiency-induced teratogenesis

The influence of a higher-than-normal intake of vitamin A on the detrimental effects of zinc deficiency on vitamin A metabolism was investigated in pregnant Sprague-Dawley rats. At mating, rats were fed diets containing 100 (control), 4.5, or 0.5 micrograms/g zinc combined with 4 (control) or 8 micrograms retinyl acetate/g. Low intake of zinc, but not of vitamin A, caused food intake, total body weight change, fetal weight and placental weight to be low. Incidence of teratogenic effects was more pronounced in low zinc groups than in controls. Concentrations of vitamin A in maternal plasma and liver were affected by the amount of zinc in the diet. Dietary vitamin A, however, did not affect either of these parameters. Maternal plasma zinc concentration was affected only by low dietary zinc, whereas plasma copper and iron were unaffected by the dietary treatments. Maternal liver iron was higher in zinc-deficient rats than in controls; however, maternal liver zinc and copper concentrations were not altered by dietary treatments. No significant differences in vitamin A concentration of fetal liver, fetal plasma, or placenta were seen among the groups. Fetuses from zinc-deficient dams had significantly lower levels of liver vitamin A and liver zinc than did controls. Fetal liver iron was higher in zinc-deficient fetuses than in controls, whereas fetal liver copper was not affected by dietary treatment. These data suggest that supplemental dietary vitamin A does not ameliorate the effect of zinc deficiency on vitamin A metabolism during pregnancy.     

Prenatal lead exposure and weight of 0- to 5-year-old children in Mexico city

Background: Cumulative prenatal lead exposure, as measured by maternal bone lead burden, has been associated with smaller weight of offspring at birth and 1 month of age, but no study has examined whether this effect persists into early childhood.Objective: We investigated the association of perinatal maternal bone lead, a biomarker of cumulative prenatal lead exposure, with children’s attained weight over time from birth to 5 years of age.Methods: Children were weighed at birth and at several intervals up until 60 months. Maternal tibia and patella lead were measured at 1 month postpartum using in vivo K-shell X-ray fluorescence. We used varying coefficient models with random effects to assess the association of maternal bone lead with weight trajectories of 522 boys and 477 girls born between 1994 and 2005 in Mexico City.Results: After controlling for breast-feeding duration, maternal anthropometry, and sociodemographic characteristics, a 1-SD increase in maternal patella lead (micrograms per gram) was associated with a 130.9-g decrease in weight [95% confidence interval (CI), –227.4 to –34.4 g] among females and a 13.0-g nonsignificant increase in weight among males (95% CI, –73.7 to 99.9 g) at 5 years of age. These associations were similar after controlling for concurrent blood lead levels between birth and 5 years.Conclusions: Maternal bone lead was associated with lower weight over time among female but not male children up to 5 years of age. Given that the association was evident for patellar but not tibial lead levels, and was limited to females, results need to be confirmed in other studies.     

Developmental toxicity induced by inhalation exposure of pregnant rats to N,N-dimethylacetamide

Developmental toxicity of N,N-dimethylacetamide (DMAC) was examined by exposing pregnant rats by inhalation to DMAC vapor at 0 (control), 100, 300, 450 or 600 ppm (v/v) for 6 h/d during Gestation Days 6 through 19. Fetal body weight and the number of male live fetuses were significantly decreased, along with a tendency of the number of intrauterine deaths to increase. The number of fetuses with visceral and skeletal malformations was significantly increased in the 450 and 600 ppm groups, while the number of fetuses with anasarca as an external malformation was increased at 600 ppm. Observed cardiovascular malformations included ventricular septum defect, persistent truncus arteriosus, malpositioned subclavian branch and retroesophageal subclavian artery. Persistent truncus arteriosus was accompanied by ventricular septal defect (VSD). Incidences of the persistent truncus arteriosus, which was classified as a serious congenital heart disease affecting postnatal survival, were increased at 450 and 600 ppm. Increased liver weights and hepatocellular swelling occurred in the dams exposed to 300 ppm and above, whereas neither hepatocellular necrosis nor increased serum activity of liver transaminases was observed in any of the exposed groups. Maternal body weights were decreased at 450 and 600 ppm. The most sensitive signs of developmental toxicity appeared at the exposure level of 300 ppm which was also the level of slight maternal toxicity. The No-Observed-Adverse-Effect-Level (NOAEL) was determined as 100 ppm for the endpoints of fetal and maternal toxicities. The NOAEL of 100 ppm and the induction of serious cardiovascular malformations occurring at 450 ppm and above were discussed with reference to the existing occupational exposure limit for DMAC.     

Maternal High-Fat Diet Reduces Type-2 Neural Stem Cells and Promotes Premature Neuronal Differentiation during Early Postnatal Development

Maternal obesity or exposure to a high-fat diet (HFD) has an irreversible impact on the structural and functional development of offspring brains. This study aimed to investigate whether maternal HFD during pregnancy and lactation impairs dentate gyrus (DG) neurogenesis in offspring by altering neural stem cells (NSCs) behaviors. Pregnant Sprague-Dawley rats were fed a chow diet (CHD) or HFD (60% fat) during gestation and lactation. Pups were collected on postnatal day 1 (PND 1), PND 10 and PND 21. Changes in offspring body weight, brain structure and granular cell layer (GCL) thickness in the hippocampus were analyzed. Hippocampal NSCs behaviors, in terms of proliferation and differentiation, were investigated after immunohistochemical staining with Nestin, Ki67, SOX2, Doublecortin (DCX) and NeuN. Maternal HFD accelerated body weight gain and brain structural development in offspring after birth. It also reduced the number of NSCs and their proliferation, leading to a decrease in NSCs pool size. Furthermore, maternal HFD intensified NSCs depletion and promoted neuronal differentiation in the early postnatal development period. These findings suggest that maternal HFD intake significantly reduced the amount and capability of NSCs via reducing type–2 NSCs and promoting premature neuronal differentiation during postnatal hippocampal development.     

Effects of dietary cadmium on mallard ducklings

Mallard (Anas platyrhynchos) ducklings were fed cadmium in the diet at 0, 5, 10, or 20 ppm from 1 day of age until 12 weeks of age. At 4-week intervals six males and six females from each dietary group were randomly selected, bled by jugular venipuncture, and necropsied. Significant decreases in packed cell volume (PCV) and hemoglobin (Hb) concentration and a significant increase in serum glutamic pyruvic transaminase (GPT) were found at 8 weeks of age in ducklings fed 20 ppm cadmium. Mild to severe kidney lesions were evident in ducklings fed 20 ppm cadmium for 12 weeks. No other blood chemistry measurement, hematological parameter, or tissue histopathological measurement indicated a reaction to cadmium ingestion. Body weight, liver weight, and the ratio of the femur weight to length were not affected by dietary cadmium. Femur cadmium concentration in all ducklings 12 weeks of age declined from the values detected at 4 and 8 weeks of age. Liver cadmium concentrations were significantly higher in relation to the increased dietary levels and in relation to the length of time the ducklings were fed the cadmium diets. At 12 weeks of age the cadmium concentration in liver tissue was twice that in the diet.     

A maternal high-fat diet represses the expression of antioxidant defense genes and induces the cellular senescence pathway in the liver of male offspring rats

Maternal high-fat (HF) diet feeding is associated with increased risk of developing metabolism-related diseases in adult offspring, including chronic liver disease. The present study tested the hypothesis that maternal HF diet leads to a decreased antioxidant defense capacity and causes cellular senescence in liver of adult offspring rats, which might increase risk of developing chronic liver disease. Timed-pregnant Sprague Dawley rats were fed a HF diet (45% of energy from fat) or a control (C) diet (16% of energy from fat) during gestation and lactation. The resulting offspring were fed a C diet after weaning to generate 2 offspring groups: C diet-fed offspring of dams fed C diet (C/C) and C diet-fed offspring of dams fed a HF diet (HF/C). At 12 wk of age, male rats were killed and samples were collected for analysis. Maternal HF diet significantly increased plasma TG and hepatic TBARS concentrations and the size of hepatic lipid droplets in offspring rats. The expression of antioxidant defense genes, such as glutathione peroxidase-1, Cu/Zn superoxide dismutase (Sod1), paraoxonase enzymes (Pon1, Pon2, and Pon3), were significantly lower in the liver of HF/C pups than in C/C pups. The expression of Inhibitor of cyclin dependent Kinase 4a (p16INK4a), a marker of cellular senescence, and cyclooxygenase-2 (Cox2), a proinflammatory marker, was significantly higher in the HF/C offspring group than in the C/C offspring group. Western-blot analysis shows that cyclin D1 and phosphorylated retinoblastoma protein were significantly lower in HF/C offspring than in C/C offspring. The results provide the first evidence to our knowledge that maternal HF diet might alter antioxidant defense capacity and program the p16INK4a-dependent cellular senescence in the liver of adult offspring.