Zebrafish (Danio rerio) fed vitamin E-deficient diets produce embryos with increased morphologic abnormalities and mortality.

The Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
The Journal of nutritional biochemistry (Impact Factor: 4.59). 06/2011; 23(5):478-86. DOI: 10.1016/j.jnutbio.2011.02.002
Source: PubMed

ABSTRACT Vitamin E (α-tocopherol) is required to prevent fetal resorption in rodents. To study α-tocopherol's role in fetal development, a nonplacental model is required. Therefore, the zebrafish, an established developmental model organism, was studied by feeding the fish a defined diet with or without added α-tocopherol. Zebrafish (age, 4-6 weeks) were fed the deficient (E-), sufficient (E+) or lab diet up to 1 years. All groups showed similar growth rates. The exponential rate of α-tocopherol depletion up to ~80 day in E- zebrafish was 0.029±0.006 nmol/g, equivalent to a depletion half-life of 25±5 days. From age ~80 days, the E- fish (5±3 nmol/g) contained ~50 times less α-tocopherol than the E+ or lab diet fish (369±131 or 362±107, respectively; P<.05). E-depleted adults demonstrated decreased startle response suggesting neurologic deficits. Expression of selected oxidative stress and apoptosis genes from livers isolated from the zebrafish fed the three diets were evaluated by quantitative polymerase chain reaction and were not found to vary with vitamin E status. When E-depleted adults were spawned, they produced viable embryos with depleted α-tocopherol concentrations. The E- embryos exhibited a higher mortality (P<.05) at 24 h post-fertillization and a higher combination of malformations and mortality (P<.05) at 120 h post-fertillization than embryos from parents fed E+ or lab diets. This study documents for the first time that vitamin E is essential for normal zebrafish embryonic development.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Tocopherols were discovered for their role in animal reproduction, but little is known about the contribution of deficiencies of vitamin E to human pregnancy loss. Objective: We sought to determine whether higher first-trimester concentrations of a-tocopherol and g-tocopherol were associated with reduced odds of miscarriage (pregnancy losses <24 wk of gestation) in women of rural Bangladesh. Design: A case-cohort study in 1605 pregnant Bangladeshi women [median (IQR) gestational age: 10 wk (8–13 wk)] who participated in a placebo-controlled vitamin A– or b-carotene–supplementation trial was done to assess ORs of miscarriage in women with low a-tocopherol (<12.0 mmol/L) and g-tocopherol (<0.81 mmol/L; upper tertile cutoff of the g-tocopherol distribution in women who did not miscarry). Results: In all women, plasma a- and g-tocopherol concentrations were low [median (IQR): 10.04 mmol/L (8.07–12.35 mmol/L) and 0.66 mmol/L (0.50–0.95 mmol/L), respectively]. In a logistic regression analysis that was adjusted for cholesterol and the other tocopherol, low a-tocopherol was associated with an OR of 1.83 (95% CI:1.04, 3.20), whereas a low g-tocopherol concentration was associated with an OR of 0.62 (95% CI: 0.41, 0.93) for miscarriage. Subgroup analyses revealed that opposing ORs were evident only in women with BMI (in kg/m2) >=18.5 and serum ferritin concentration <=150 mg/L, although low BMI and elevated ferritin conferred stronger risk of miscarriage. Conclusions: In pregnant women in rural Bangladesh, low plasma a-tocopherol was associated with increased risk of miscarriage, and low g- tocopherol was associated with decreased risk of miscarriage. Maternal vitamin E status in the first trimester may influence risk of early pregnancy loss. The JiVitA-1 study, from which data for this report were derived, was registered at as GHS-A-00-03-00019-00.
    American Journal of Clinical Nutrition 11/2014; 101(2). DOI:10.3945/ajcn.114.094920 · 6.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is estimated that >90% of Americans do not consume sufficient dietary vitamin E, as α-tocopherol, to meet estimated average requirements. What are the adverse consequences of inadequate dietary α-tocopherol intakes? This review discusses health aspects where inadequate vitamin E status is detrimental and additional vitamin E has reversed the symptoms. In general, plasma α-tocopherol concentrations <12 μmol/L are associated with increased infection, anemia, stunting of growth, and poor outcomes during pregnancy for both the infant and the mother. When low dietary amounts of α-tocopherol are consumed, tissue α-tocopherol needs exceed amounts available, leading to increased damage to target tissues. Seemingly, adequacy of human vitamin E status cannot be assessed from circulating α-tocopherol concentrations, but inadequacy can be determined from “low” values. Circulating α-tocopherol concentrations are very difficult to interpret because, as a person ages, plasma lipid concentrations also increase and these elevations in lipids increase the plasma carriers for α-tocopherol, leading to higher circulating α-tocopherol concentrations. However, abnormal lipoprotein metabolism does not necessarily increase α-tocopherol delivery to tissues. Additional biomarkers of inadequate vitamin E status are needed. Urinary excretion of the vitamin E metabolite α-carboxy-ethyl-hydroxychromanol may fulfill this biomarker role, but it has not been widely studied with regard to vitamin E status in humans or with regard to health benefits. This review evaluated the information available on the adverse consequences of inadequate α-tocopherol status and provides suggestions for avenues for research.
    Advances in Nutrition 09/2014; 5(5):503-14. DOI:10.3945/an.114.006254 · 4.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The composition of the typical commercial diet fed to zebrafish can dramatically vary. By utilizing defined diets we sought to answer two questions: 1) How does the embryonic zebrafish transcriptome change when the parental adults are fed a commercial lab diet compared with a sufficient, defined diet (E +)? 2) Does a vitamin E-deficient parental diet (E-) further change the embryonic transcriptome? We conducted a global gene expression study using embryos from zebrafish fed a commercial (Lab), an E + or an E- diet. To capture differentially expressed transcripts prior to onset of overt malformations observed in E- embryos at 48 hours post-fertilization (hpf), embryos were collected from each group at 36 hpf. Lab embryos differentially expressed (p < 0.01) 946 transcripts compared with the E + embryos, and 2,656 transcripts compared with the E- embryos. The differences in protein, fat and micronutrient intakes in zebrafish fed the Lab compared with the E + diet demonstrates that despite overt morphologic consistency, significant differences in gene expression occurred. Moreover, functional analysis of the significant transcripts in the E- embryos suggested perturbed energy metabolism, leading to overt malformations and mortality. Thus, these findings demonstrate that parental zebrafish diet has a direct impact on the embryonic transcriptome.
    Comparative Biochemistry and Physiology Part D Genomics and Proteomics 06/2014; DOI:10.1016/j.cbd.2014.02.001 · 2.82 Impact Factor