Evaluation of dietary essentiality of vitamins for Penaeus monodon (Fabricius)

The effect of exclusion of individual water-soluble (thiamine, riboflavin, pyridoxine, cyanocobalamin, pantothenic acid, folic acid, niacin, biotin, choline, inositol, ascorbic acid) and fat-soluble vitamins (vit. A, D, K and E) in semi-purified diets on growth and survival of juvenile shrimp, P. monodon was studied in the laboratory for 8 weeks. Diets lacking riboflavin and vitamin K did not affect growth and survival of shrimp. However, deletion of inositol and choline resulted in poor growth. Maximum growth was observed in the control diet (C1) which was supplemented with all vitamins. Diet deficient in ascorbic acid, biotin, folic acid, niacin, thiamine and alpha-tocopherol resulted in poor appetite and poorer feed conversion efficiency. All treatments except the control (C1) resulted in histological changes in the digestive gland cells. Detachment or destruction of the epithelial cells was observed in all treatments lacking individual vitamins but more severely in the treatment without a vitamin supplement followed by inositol, choline and ascorbic acid deficient diets.     

On the physiology of the red alga Asterocytis ramosa in axenic culture

The red alga Asterocytis ramosa has been cultivated aseptically in artificial seawater ASP6 F. The alga shows optimal growth at 22·5–25° C. Optimal light conditions as well as phosphorus and nitrogen requirements were investigated. Nitrate and ammonium salts as well as organic nitrogen can be used as a nitrogen source. Arginine was an extremely good source of nitrogen, presumably because it splits off urea. Asterocytis is vitamin B₁₂ heterotrophic and growth is obtained with cyanocobalamin, Factor III and Factor Z₁. A mixture of other vitamins gives further stimulation. In the newly isolated culture, hexoses and pentoses enhanced growth. Acetate increased growth in an old axenic culture. In darkness no growth was obtained.     

Mutagenic activity of pyrolysates of cyanocobalamin and some other water-soluble vitamins in the model system with the Salmonella/mammalian microsomes

Pyrolysates of cyanocobalamin, thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, and ascorbic acid were tested for mutagenicity in the histidine-requiring mutants Salmonella typhimurium TA98 and TA100. Each vitamin was sealed in a glass tube and heated at 100-600 degrees C in a muffle furnace. Methanol-chloroform extracts of the pyrolysate of each vitamin tested did not show any mutagenicity in either TA98 or TA100 without rat liver 9000 x g supernatant fraction (S9) added. In the presence of S9, the B-group vitamins (cyanocobalamin, thiamine hydrochloride, riboflavin, and pyridoxine hydrochloride) were all mutagenic in TA98 and TA100, with the highest activity among the vitamins tested found in the pyrolysate of cyanocobalamin. The pyrolysate of 0.25 mumole cyanocobalamin produced 3200 revertants, while the pyrolysates of 0.25 mumole thiamine hydrochloride and riboflavin produced only 910 revertants, and the pyrolysate of pyridoxine hydrochloride did not show any mutagenicity at that amount. The mutagenicity was generally more active to TA98 than to TA100, indicating that frameshift-type mutagens were contained in the pyrolysates. The pyrolysate of ascorbic acid did not show any mutagenic activity in either TA98 or TA100 under the present experimental conditions.     

Effect of metal specific amino acid complexes and inorganic trace minerals on vitamin stability in premixes

Stability of vitamin activity in a swine premix containing metal specific amino acid complexes, inorganic trace minerals, or no trace minerals was evaluated over a 120-day storage period. Two vitamin-trace mineral premixes containing either metal specific amino acid complexes or inorganic trace mineral sources were formulated to contain 200% of NRC (1988) sow requirements for I, Cu, Zn, Mn, Fe, and Se based on a 5 g/kg dietary inclusion rate. A separate vitamin premix containing no trace minerals served as the control. The vitamin premix and the two vitamin-trace mineral premixes were formulated to contain the same level of vitamins. Vitamin levels exceeded NRC (1988) and were chosen to represent “typical” industry levels based on an informal survey of vitamin levels in commercial premixes in the U.S.A. Premixes were stored in an environmentally controlled feed storage room and samples were collected every month to determine vitamin activity. Minimal monthly vitamin stock losses in activity (0–1%) were observed for all vitamins except cyanocobalamin (2.8%) and choline (1.3%). Pantothenate, vitamin E, riboflavin, biotin and niacin were most resistant to destruction, while menadione, retinol, vitamin B-6, and thiamine were subject to the greatest loss of activity during the 120-day storage period. Use of metal specific amino acid complexes in vitamin-trace mineral premixes significantly reduced the loss of retinol, menadione, cyanocobalamin, thiamine, folates, vitamin B-6, and choline activity (P<0.05) compared to losses of vitamin activity in premixes containing inorganic trace minerals. Activity losses in retinol, cyanocobalamin, thiamine, and choline were similar between the vitamin premix and the vitamin-complexed trace mineral premix. Biotin activity was undetectable in the vitamin-complexed trace mineral premix due to unexplained analytical interference. Each vitamin was ranked according to relative vitamin assay cost, loss in vitamin activity per month, and susceptibility to multiple stress factors. This ranking was used to identify vitamins that could represent overall vitamin activity in a premix and could be assayed at a reasonable cost for a feed manufacturing quality control program. Retinol was identified as the best indicator vitamin, followed by thiamine, menadione, and cyanocobalamin. These results suggest that vitamin stability in swine vitamin-trace mineral premixes is improved when using metal specific amino acid complexes compared to inorganic trace mineral sources. More liberal safety margins for vitamins may be needed when formulating vitamin-trace mineral premixes using inorganic sources of trace minerals.     

Biosynthesis of vitamins B by the fungus Pleurotus ostreatus in a submerged culture

The intra- and extracellular contents of vitamins were studied in the course of submerged cultivation of the higher basidial mushroom Pleurotus ostreatus (Jacq.: Fr.) Kummer st. IMBF-1300 on liquid nutrient media. This strain was found to be autotrophic in respect of thiamin (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B5), pyridoxine (vitamin B6) and biotin (vitamin B7), but it failed to synthesize cyanocobalamin (vitamin B12). The composition and pH of the culture medium, containing such complex biostimulating supplements as maize extract and concentrated potato sap noticeably influence the contents of vitamins B1, B5 and B7 in the mycelium, and to a less degree they change the level of the intracellular biosynthesis of vitamins B2 and B6. Higher excretion of vitamins B5, B7 and especially B6 was observed on the semisynthetic media during the postexponential growth. Under experimental conditions vitamins B1 and B2 were accumulated only in the cells. The dry mycelium of P. ostreatus obtained by submerged cultivation on liquid media is a valuable source of B vitamins and, especially, of niacin. Thus the oyster mushroom and other edible mushrooms can be put at one of the top places among food-stuffs by the content of niacin.     

Growth kinetics of Chinese hamster ovary cells in a compact loop bioreactor. 3. Selection and characterization of an anchorage-independent subline and medium improvement.

Four sublines of Chinese hamster ovary (CHO) cells were selected or cloned on a 10% fetal calf serum supplemented MEM-alpha medium. Three of them were monolayer cultures and could proliferate by 2000 times a week (mu = 1.1 d 1) in T-flasks. The other subline, S1, could grow in suspension even in static T-flask cultures. The stability in chromosome number of these cell lines was investigated. By evaluating the kinetic growth parameters, i.e. the specific rates of growth, glucose consumption and lactic acid production, and the yields of cells and lactic acid from glucose, the S1 cells were considered to be the most suitable subline for the bioreactor suspension culture. The S1 cells reached the greatest maximum of cell concentration among all cell lines tested because of their efficient glucose utilization. Observed nutrient limitations in the S1 cell culture was overcome by modification of the medium composition, that is addition of 10 mg l-1 hypoxanthine, 1 mg l-1 FeSO4.7H2O, and 0.1 mg l-1 sodium putrescine, elimination of glutamine, supplementation of 6 mM asparagine and double amount of isoleucine, leucine, methionine and vitamins other than ascorbic acid, cyanocobalamin and biotin, increase of NaHCO3 concentration from 26 to 40 mM, and finally decrease of NaCl concentration from 122 to 100 mM. With this modified medium, 7.2 X 10(6) ml-1 of the maximum cell concentration was observed in a glucose fed-batch culture, the cell concentration which was twice as much as in batch cultures with the original medium.     

Effect of nutrients on the growth of a new alpine strain of Haematococcus (Chlorophyceae) from New Zealand

The microalga Haematococcus lacustris is a source of astaxanthin used widely in aquaculture, pharmaceutical, and cosmetic industries. A new strain of Haematococcus (LCR‐26C‐1f) isolated from the New Zealand alpine zone was evaluated in this study. The influence of vitamins, micronutrients, various carbon and nitrogen sources were investigated to maximize biomass production in batch cultures using shake flasks. Supplementation of vitamins consisting of thiamine, biotin, and cyanocobalamin improved the cell density by 40% over the vitamin‐free medium. Out of the individual vitamins tested, thiamine was shown to be necessary to maintain high cell densities. The best nitrogen source tested was nitrate in the form of sodium nitrate_, at a 40 mM concentration. Heterotrophic growth yielded much lower cell densities compared to autotrophic growth. The micronutrients iron and manganese were essential for growth. However, the best growth was obtained using a micronutrient mix that included iron, copper, cobalt, zinc, manganese and molybdenum.     

Biosynthesis of folic acid

Summary The influence of various vitamins on the biogenesis of folic acid has been studied in microorganisms requiring these as growth factors. In L. arabinosus, the folic acid synthesised was directly proportional to the availability of both riboflavin and pantothenic acid. The influence of cyanocobalamin on folic synthesis varied radically in different organisms. In case of the B₁₂/methionine auxotroph of E. coli there was an inverse relationship of vitamin B₁₂ to folic acid synthesis, while in Euglena the folic acid elaborated was in proportion to cyanocobalamin supplied. Synthesis of both folic acid and vitamin B₁₂ was depressed when thymine supply was adequate in the nutrition of E. coli 15 T ^-, a thymine auxotroph.     

Transient responses of hybridoma cells in continuous culture to step changes in amino acid and vitamin concentrations

The effects of step-change increase in the concentrations of amino acids and vitamins on the metabolism, growth, and antibody productivity of a murine hybridoma cell line grown in continuous culture on serum-free medium are presented. Additions of the amino acids cysteine with methionine, tryptophan, and isoleucine with valine and vitamin B(12) (as cyanocobalamin) resulted in significant increases in viable cell concentrations. Additions of aspartate with asparagine, and threonine with vitamin B(1) (as thiamine hydrochloride) resulted in significant increases in final antibody concentrations. Substantial decrease in the fraction of amino acid nitrogen excreted as ammonia occurred upon supplementation with three times the normal concentrations of branched chain amino acids. Decreases in the fraction of amino acid nitrogen converted to ammonia were paralleled by increases in the fraction converted to alanine. (c) 1994 John Wiley & Sons, Inc.     

Vitamin requirements for development of eight-cell hamster embryos to hatching blastocysts in vitro

We have shown in previous studies that development of 8-cell hamster embryos to hatching and hatched blastocysts in vitro is stimulated by the addition to the culture medium of a group of 11 water-soluble vitamins and growth factors from Ham's F10 medium. In the present study, the requirement for each of these vitamins for blastocyst hatching was examined by using a chemically defined protein-free medium. Eight-cell hamster embryos were cultured for 3 days either in medium with all 11 vitamins or in media with a single vitamin omitted at a time or in medium without any vitamins. The only vitamins whose omission caused a significant decrease in blastocyst hatching at any stage were inositol, pantothenate, and choline, with the omission of inositol having the most severe effect. This finding was confirmed in a subsequent experiment in which the addition of these 3 vitamins stimulated the same degree of hatching as all 11 vitamins.     

Conversion and Distribution of Cobalamin in Euglena gracilis z, with Special Reference to Its Location and Probable Function within Chloroplasts

Cobalamin is essentially required for growth by Euglena gracilis and shown to be converted to coenzyme forms promptly after feeding cyanocobalamin. Concentrations of coenzymes, methylcobalamin, and 5′-deoxyadenosylcobalamin, reached about 1 femtomole/10⁶ cells 2 hours after feeding cyanocobalamin to cobalamin-limited cells. Cobalamins all were bound to proteins in Euglena cells and located in subcellular fractions of chloroplasts, mitochondria, microsomes, and cytosol. Incorporated cobalamin into chloroplasts was localized in thylakoids. Methylcobalamin existed in chloroplasts, mitochondria, and cytosol, while 5′-deoxyadenosylcobalamin was in mitochondria and the cytosol, 2 h after feeding cyanocobalamin to Euglena cells. Quantitative alterations of methylcobalamin and 5′-deoxyadenosylcobalamin in chloroplasts suggest their important functions as coenzymes in this organelle. The occurrence of functional cobalamins in chloroplasts has not been reported in other photosynthetic eukaryotes.     

Role of alpha-tocopherol and retinol in the antiradical protection of the body in peptic ulcer]

Retinol and tocopherol content, the intensity of spontaneous chemiluminescence as well as concentration of malonic dialdehyde in the blood of practically healthy persons of different age groups and in patients with gastric and duodenal ulcer have been studied. Results are presented. The lower content of tocopherol was revealed in the young persons as compared with other age groups, while the level of vitamin A was not established to depend on age. The content of tocopherol is established to decrease in the blood serum under peptic ulcer. Under these conditions low level of retinol correlates with considerable growth of spontaneous chemiluminescence. Reserve interrelation of tocopherol content in the blood with the level of spontaneous chemiluminescence as well as the absence of true dependence on the concentration of malonic dialdehyde at peptic ulcer are proved. Mechanisms of participation of vitamins E and A in the inhibition of free-radical reactions are discussed, role of their deficiency in pathogenesis fo peptic ulcer is substantiated.     

Multiple antibiotics produced by Pseudomonas fluorescens HV37a and their differential regulation by glucose

Pseudomonas fluorescens HV37a inhibited growth of the fungus Pythium ultimum on potato dextrose agar (PDA). An antibiotic activity produced under these conditions was fractionated and partially characterized. Extracts prepared from the PDA on which HV37a was grown revealed a single peak of antibiotic activity on thin-layer chromatograms. Similar extracts were prepared from mutants of HV37a. Their analysis indicated that the antibiotic observed in thin-layer chromatograms was responsible for fungal inhibition observed on PDA. The production of the PDA antibiotic required the presence of glucose, whereas two other antibiotic activities were produced only on potato agar without added glucose. Two mutants (denoted AfuIa and AfuIb) previously characterized as deficient in fungal inhibition on PDA showed altered regulation of the production of all three antibiotics in response to glucose. These mutants were also deficient in glucose dehydrogenase. Mutants isolated as deficient in glucose dehydrogenase were also deficient in fungal inhibition and were grouped into two classes on the basis of complementation analysis with an AfuI cosmid. Glucose regulation of antibiotic biosynthesis therefore involves at least two components and requires glucose dehydrogenase.     

Effects of a diet deficient in the B complex vitamins on infectivity, growth and distribution of Echinostoma caproni in ICR mice

The effects of a diet deficient in the B vitamins on infectivity, growth, and distribution of Echinostoma caproni in ICR mice were studied. The vitamin-deficient diet (experimental) was isocaloric to the control diet but lacked the B vitamins. Thirty-six female, 6- to 8-week-old ICR mice were each infected with 25 metacercarial cysts. From the day of infection to the day of necropsy, 18 mice were fed the experimental diet and the remaining mice received the control diet. Equal numbers of experimental and control mice were necropsied at 2, 3 and 4 weeks postinfection (p.i.). Mice on the experimental diet showed a significant loss in body weight between 2 and 4 weeks p.i. There was no significant difference in worm recovery at 2 to 4 weeks p.i. from mice on either diet. Worms from hosts on the experimental diet were more dispersed and located more posteriad in the small intestine than those from mice on the control diet. Worm dry weight was significantly less in hosts on the experimental diet at all weeks p.i. compared with that of hosts on the control diet. The body area of worms on the experimental diet was significantly less at 2 and 3 weeks p.i. than that of worms on the control diet. An isocaloric diet deficient in the B vitamins had a detrimental effect on the growth of E. caproni in ICR mice.     

Identification and quantitation of corrinoid precursors of cobalamin from Pseudomonas denitrificans by high-performance liquid chromatography

After initial pretreatment for removal of interfering substances, corrinoid precursors of cobalamin from cultures of Pseudomonas denitrificans were separated by HPLC with a gradient elution system. In this system, all the following compounds are separated in their dicyano form, and retention times are given: cobyrinic acid; cobyrinic acid a-amide; cobyrinic acid c-amide; cobyrinic acid g-amide; cobyrinic acid a,g-diamide; cobyrinic acid c,g-diamide; cobyrinic acid a,c-diamide; cobyrinic acid a,c,g-triamide; cobyrinic acid triamide, tetraamide, and pentaamide isolated from P. denitrificans; cobyric acid; cobinamide; cobinamide phosphate; GDP-cobinamide; cyanocobalamin 5'-phosphate; and cyanocobalamin. Application of this HPLC method to culture samples of P. denitrificans revealed that in this microorganism the level of cobyrinic acid and cobyrinic acid monoamide is far lower than that of all other corrinoid precursors of cobalamin and suggested that (i) the (R)-1-amino-2-propanol group is incorporated only after completion of all the other amidations and (ii) the amidations follow only one sequence. The usefulness of this HPLC method was further demonstrated by identifying the 57Co-labeled corrinoid precursors of cobalamin accumulated by cobalamin-deficient mutants of Agrobacterium tumefaciens. A TLC system that separates the different corrinoid intermediates (in their dicyano form) and cyanocobalamin is also described.     

Stimulation of heterotrophic and autotrophic growth ofSphaerotilus discophorus by manganous ions

Growth ofS. discophorus in a casamino acids-mineral salts medium was stimulated 3-fold on addition of 0.05% MnSO₄·H₂O to the medium. Growth was measured by determinations of total nitrogen, protein and DNA on the washed cellular material.Autotrophic growth ofS. discophorus strain 43-R was obtained in an inorganic mineral salts medium supplemented with trace amounts of the essential vitamins, thiamin, biotin and cyanocobalamin and with Mn⁺⁺ as the sole available source of energy. A gas mixture of 5% CO₂-95% air was bubbled continuously through the cultures during incubation. Concomitant with growth, Mn⁺⁺ disappeared from the cultures and MnO₂ was formed.     

The quantitative requirements of human diploid cells (strain MRC-5) for amino acids, vitamins and serum.

The uptakes of all essential amino acids, vitamins (except riboflavin), glucose and serum during growth of human diploid cells (MRC-5) were determined. The amino acid uptakes varied considerably with the conditions of culture. The glucose requirement is several times greater than that for mouse LS or human HeLa cells. These analytical results were used to modify the medium so as to ensure that an excess of all defined medium constituents was present and pH was not limiting during study of the serum requirements. It was then found that maximum cell populations were directly proportional to the serum concentration. Hence the growth was limited by the supply of an unknown growth factor in serum. The serum growth factor was not replaced by a mixture of over 60 vitamins, co-enzymes, hormones and other organic and inorganic compounds considered to be possible growth factors, although this mixture did not lower the growth rate and somewhat (22%) increased the yield from the serum growth factor. The unit of serum growth factor is precisely defined in terms of the amount in a standard batch of calf serum. This standard contains 10 units/ml whereas the other batch of serum used contained only 5 units/ml.     

A glyphosate-based herbicide disrupted hematopoiesis and induced organ toxicities,ameliorated by vitamin B12 in a mouse model

Glyphosate-based herbicides (GBH) are widely used worldwide. Their negative impact on human health is a matter of debate by regulatory bodies and the public. The present study sought to determine the impact of a GBH on the vital organs; and the potential protective effects of vitamin B12 (cyanocobalamin) supplementation. Sixty white Swiss mice were randomly assigned to five treatment groups, each containing twelve mice. Group one represented the normal control; Group two mice were treated with 375 mg/kg of GBH for 56 days; Group three mice received 10 mg/kg of cyanocobalamin for 56 days; Group four mice were administered with 375 mg/kg of GBH and 10 mg/kg cyanocobalamin for 56 days and Group five received 10 mg/kg cyanocobalamin first for 7 days, then continued thereafter co-administered together with 375 mg/kg of GBH for 56 days). Oral administration of GBH induced severe anemia in mice, which was attenuated by cyanocobalamin. Moreover, GBH resulted in a very significant alteration of platelets, WBCs, and its sub-types. Once again, cyanocobalamin stabilized the levels of platelets and WBCs in the presence of GBH. GBH-induced elevation of triglycerides and HDL was nullified by the administration of cyanocobalamin. Further studies showed evidence for GBH-induced inflammation represented by an imbalance in serum levels of the TNF-α: IL-10 and IFN-γ ratios. The GBH severely depleted GSH levels in the liver. A GBH-induced rise in GSH in the kidney, lungs and brain was noted; and is an indicator of antioxidant capacity enhancement in response to a GBH-induced oxidant challenge. Moreover, cyanocobalamin supplementation abrogated GBH-induced oxidative stress as depicted by stabilized GSH levels in the liver, kidney, lungs, and brain. In the presence of cyanocobalamin, the GBH-induced liver injury depicted by elevation of AST, ALT, and bilirubin, was attenuated. From the results, we conclude that the capacity of cyanocobalamin to assuage GBH-induced inflammatory responses, hepatotoxicity, and hematological alteration as well as oxidative stress may be attributable to its antioxidant and anti-inflammatory properties. The current findings provide a solid foundation for further scrutiny of this phenomenon, with vital implications in GBH exposure and the role of potent antioxidant supplementation in the management of GBH-induced toxicity.     

A mutation in Flavobacterium psychrophilum tlpB inhibits gliding motility and induces biofilm formation

Flavobacterium psychrophilum is a psychrotrophic, fish-pathogenic bacterium belonging to the Cytophaga-Flavobacterium-Bacteroides group. Tn4351-induced mutants deficient in gliding motility, growth on iron-depleted media, and extracellular proteolytic activity were isolated. Some of these mutants were affected in only one of these characteristics, whereas others had defects in two or more. FP523, a mutant deficient in all of these properties, was studied further. FP523 had a Tn4351 insertion in tlpB (thiol oxidoreductase-like protein gene), which encodes a 41.4-kDa protein whose sequence does not exhibit high levels of similar to the sequences of proteins having known functions. TlpB has two domains; the N-terminal domains has five transmembrane regions, whereas the C-terminal domains has the Cys-X-X-Cys motif and other conserved motifs characteristic of thiol:disulfide oxidoreductases. Quantitative analysis of the thiol groups of periplasmic proteins revealed that TlpB is required for reduction of these groups. The tlpB gene is part of the fpt (F. psychrophilum thiol oxidoreductase) operon that contains two other genes, tlpA and tpiA, which encode a thiol:disulfide oxidoreductase and a triosephosphate isomerase, respectively. FP523 exhibited enhanced biofilm formation and decreased virulence and cytotoxicity. Complementation with the tlpB loci restored the wild-type phenotype. Gliding motility and biofilm formation appear to be antagonistic properties, which are both affected by TlpB.     

叶酸缺乏致胎鼠宫内发育迟缓及肝脏胰岛素生长因子系统表达变化

目的：叶酸是一种水溶性B族维生素,在体内氨基酸与核苷酸代谢中起重要作用,是胎儿生长发育所必须的营养素。本文通过建立叶酸缺乏的孕鼠模型,探讨叶酸缺乏对胎鼠宫内发育的影响,并研究胎鼠肝脏组织中胰岛素生长因子（IGF）系统的表达变化。方法：雌性C57BL／6J小鼠叶酸缺乏组6只、正常对照组6只,分别饲以不舍叶酸和含2mg叶酸／kg的纯合饲料。四周后与雄鼠交配,于怀孕第13．5天（13．5dpc）对孕鼠剖腹取胎,观察和评价胎鼠发育指标,并对宫内发育迟缓（IUGR）比率进行统计。用Real-timePCR法检测胎鼠肝脏组织中胰岛素生长因子I（IGFI）、胰岛素生长因子I受体（IGFIR）、胰岛素生长因子II（IGFII）、胰岛素生长因子II受体（IGFIIR）、胰岛素生长因子结合蛋白1（IGFBP-1）和胰岛素生长因子结合蛋白3（IGFBP-3）mRNA的相对表达水平。结果：叶酸缺乏组雌鼠合笼前每日体重增长量降低,13．5dpc胎鼠吸收胎和死胎比率升高,胎重下降,IUGR比率显著升高,差异有统计学意义（P〈0．05）;叶酸缺乏组胎鼠肝脏组织中IGFII和IGFIIRmRNA的相对表达水平均低于正常对照组（P〈0．05）,IGFI、IGFIR、IGFBP-1和IGFBP-3mRNA的相对表达水平两组间没有差异（P〉0．05）。结论：叶酸缺乏会导致小鼠孕中期胎鼠IUGR比率升高及胎肝IGFII和IGFIIRmRNA的表达水平降低,提示叶酸缺乏对IGF系统基因的调控,可能与胎鼠I-UGR发生机制有关。