ZD Group Research Articles

Moderate Zinc Deficiency Reduces Testicular Zip6 and Zip10 Abundance and Impairs Spermatogenesis in Mice1–3

Male infertility accounts for ~40% of cases of failure to conceive. Testes have a strict zinc (Zn) requirement and severe Zn deficiency compromises spermatogenesis, sperm viability, and motility, compromising fertility in men. Despite the high prevalence of marginal Zn deficiency in humans, less emphasis has been placed on understanding the consequences on male reproduction. Swiss Webster mice were used to visualize Zip protein expression during spermatogenesis using immunohistochemistry. Data suggest Zip5 imports Zn into Sertoli cells and spermatocytes, augmented by Zip10 (primary spermatocytes) and Zip8 (secondary spermatocytes). Zip6, 8, and 10 expression was retained in round spermatids, although Zip8 and Zip10 expression disappears during spermatid maturation. Zip1 and Zip6 expression was detected in mature, elongated spermatids. Zip14 was detected in undifferentiated spermatogonia and Leydig cells. Mice fed diets (n = 10/group) reduced in Zn concentration [marginal-Zn diet (MZD), 10 mg Zn/kg; low-Zn diet (ZD), 7 mg Zn/kg] for 30 d had >35% lower liver Zn concentrations than mice fed the control diet (C; 30 mg Zn/kg) (P < 0.05). Plasma Zn and testosterone concentrations and the testes Zn concentration and weight were not significantly lower than in controls. Plasma Zn was greater in the ZD group than in the C and MZD groups. Mice fed ZD had a reduced number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells (~50%; P < 0.05), compromised seminiferous tubule structure, and reduced Zip10 and Zip6 abundance (>50%; P < 0.5) compared with mice fed C. Our data provide compelling evidence that reduced Zn intake may be associated with infertility in men, perhaps independent of decreased levels of circulating Zn or testosterone, which warrants further investigation in human populations.

Effects of Zinc Supplementation and Deficiency on Bone Metabolism and Related Gene Expression in Rat

One hundred male rats were randomly divided into four groups (n = 25) and fed a Zn-adequate diet (ZA, 46.39 mg/kg), Zn-deficient diet (ZD, 3.20 mg/kg), Zn-overdose diet (ZO, 234.39 mg/kg), or were pair-fed a Zn-adequate diet (PF) for 5 weeks, respectively. The body weight, femur weight, and activity of alkaline phosphatase (ALP) were reduced in the ZD group but were increased in the ZO group. Zn concentrations in both liver and femur were elevated in the ZO group, whereas femur Zn was decreased in the ZD group. The concentrations of calcium and phosphorus were lower in the ZD than those in other groups. Serum calcium concentration was decreased in the ZD. The relative expression level of ALP was decreased in both ZD and PF, and no significant differences were observed between ZO and ZA. Insulin-like growth factor-I (IGF-I) mRNA level was reduced in the ZD but unchanged in the ZO and PF group. Zn deficiency also decreased ALP mRNA level as compared with that of PF group. Carbonic anhydrase II mRNA level was not affected by Zn. Nevertheless, dietary Zn influenced the growth, bone metabolism, and expression of IGF-I and ALP in male growing rats.

Effects of Zinc Deficiency on Colonic Microbiota

The purpose of this study was to evaluate colonic microbiota composition in response to a dietary zinc deficiency in mice. Male, 12‐wk‐old CD‐1 mice (n=5/ diet group) were fed a zinc adequate (ZA, 30.0 ppm) or a zinc deficient (ZD, 0.85 ppm) diet for 4 weeks. Transcript levels of colonic metallothionein (MT) and the zinc transporter (Zip4) were measured by qPCR as markers of zinc status. MT mRNA levels decreased by 0.55 fold (p=0.032) while Zip4 mRNA levels increased 2.88 fold (p=0.016). ZD mice didn't experience weight loss normally associated with deficiency. However, there was a difference in weight gain (6.9%± 1.6 vs. 3.6%± 1.1, p=0.01) in ZA and ZD mice, respectively. Microbiota composition was analyzed by denaturing gradient gel electrophoresis (DGGE) analysis and 16S rRNA sequencing. Initial DGGE profiling suggested that ZA and ZD groups differed in intestinal microbiota composition. 454 based 16S rRNA sequencing identified various phylotypes that, at the level of 99% identity, showed significant differences (p≤0.05) between the two diet groups. Weighted UniFrac analysis of overall microbiota composition indicated that ZD grouped separately from ZA, suggesting that a 4‐week zinc deficient diet alters overall colon microbiota composition in mice. Sponsored by the University of Florida University Scholars Program

The influence of gestational zinc deficiency on the fetal insulin-like growth factor axis in the rat

The insulin-like growth factor (IGF) axis, a key regulator of embryonic growth and development, is exquisitely sensitive to the nutrient status of the animal. In addition to macronutrient deficiencies, zinc deficiency can impact the IGF axis. Gestational zinc deficiency is teratogenic, resulting in intrauterine growth retardation and structural abnormalities. The aim of this study was to investigate the effects of gestational zinc deficiency on the fetal IGF axis in a rat model. From gestation day (GD) 0.5, dams consumed zinc-deficient (ZD, 0.3 mg zinc/kg) or control (25 mg zinc/kg) diet ad libitum, while a third group of dams consumed the control diet in amounts equivalent to the food intake of the ZD dams (Paired group). On GD 19.5 fetal tissue, blood and amniotic fluid were collected. Fetal growth was significantly reduced by zinc deficiency compared with the Paired and Control groups. Fetuses from the Paired group were smaller compared with the Control, but only ZD fetuses had structural malformations. Amniotic fluid IGF-1 concentrations were significantly lower in the Paired group than in the ZD and Control groups. Plasma of ZD fetuses contained lower levels of IGF binding protein-1 when compared with fetuses in the Paired and Control groups. Fetal liver IGF-1 mRNA levels were lower in the ZD fetuses than in the Paired and Control fetuses. These observations suggest that differences in the fetal IGF axis between ZD and Paired groups contribute to the poor pregnancy outcome and enhanced fetal growth retardation observed with zinc deficiency.

Gestational zinc deficiency affects the regulation of transcription factors AP-1, NF-κB and NFAT in fetal brain

Transcription factors AP-1, nuclear factor κB (NF-κB) and NFAT are central to brain development by regulating the expression of genes that modulate cell proliferation, differentiation, apoptosis and synaptic plasticity. This work investigated the consequences of feeding zinc-deficient and marginal zinc diets to rat dams during gestation on the modulation of AP-1, NF-κB and NFAT in fetal brain. Sprague–Dawley rats were fed from gestation day (GD) 0 a control diet ad libitum (25 μg zinc/g diet, C), a zinc-deficient diet ad libitum (0.5 μg zinc/g diet, ZD), the control diet in the amounts eaten by the ZD rats (restrict fed, RF) or a diet containing a marginal zinc concentration ad libitum (10 μg zinc/g diet, MZD) until GD 19. AP-1-DNA binding was higher (50–190%) in nuclear fraction isolated from ZD, RF and MZD fetal brains compared to controls. In MZD fetal brain, high levels of activation of the upstream mitogen-activated protein kinases JNK and p38 and low levels of ERK phosphorylation were observed. Total levels of NF-κB and NFAT activation were higher or similar in the ZD and MZD groups than in controls, respectively. However, NF-κB- and NFAT-DNA binding in nuclear fractions was markedly lower in ZD and MZD fetal brain than in controls (50–80%). The latter could be related to zinc deficiency-associated alterations of the cytoskeleton, which is required for NF-κB and NFAT nuclear transport. In summary, suboptimal zinc nutrition during gestation could cause long-term effects on brain function, partially through a deregulation of transcription factors AP-1, NF-κB and NFAT.

Effects of zinc levels on activities of gastrointestinal enzymes in growing rats

The present study investigated the effect of different zinc (Zn) levels on activities of gastrointestinal digestive enzymes of growing rats. Four diets including Zn-adequate (ZA; 46 mg/kg, control), Zn-deficient (ZD; 3 mg/kg), high Zn supply (ZH; 234 mg/kg) and pair-fed in which animals received the ZA diet at restricted amounts reflecting feed intake of the ZD group were fed to rats for 5 weeks. Dietary Zn was supplemented with ZnO. The results showed that Zn deficiency resulted in decreases in body weight, while ZH supply stimulated growth. The activities of sucrase, lactase and lipase were unaffected by dietary Zn levels. Maltase activity, however, was reduced in ZD group and elevated in ZH group. Amylase and protease activities were depressed by zinc deficiency. However, rats fed the Zn-repletion diet displayed higher activity of pepsin, pancreatic amylase and protease. In particular, ZH supply did have no effect on intestinal hydrolases activities. The present study suggested that zinc deficiency impaired the activities of digestive enzymes and growth of animals. However, ZH supply might improve the digestion of nutrients via increasing activities of gastrointestinal hydrolase and probably enhanced animal health.

Relationship between abnormal sperm morphology induced by dietary zinc deficiency and lipid composition in testes of growing rats

The present study investigated the effect of dietary Zn deficiency during sexual maturation on sperm integrity and testis phospholipid fatty acid composition. Male weanling Sprague-Dawley rats were randomised into four dietary groups for 3 weeks: Zn control (ZC; 30 mg Zn/kg); Zn marginally deficient (ZMD; 9 mg Zn/kg); Zn deficient (ZD; < 1 mg Zn/kg); pair fed (PF; 30 mg Zn/kg) to the ZD group. Morphology of cauda epididymal sperm and lipid profiles of testis phospholipids were analysed. The rats fed the ZD diet had a lower testis weight (P < 0.02). Seminal vesicles and prostate weight were also lower in the ZD and PF groups. Rats fed the ZD diet, but not the ZMD diet, had 34-35 % more abnormal spermatozoa and 24 % shorter sperm tail length than the ZC and PF rats (P < 0.001). Testis cholesterol concentration was higher in the ZD rats compared with the ZC and PF rats (P < 0.04). Testes were highly enriched with n-6 fatty acids by showing n-6 : n-3 fatty acid ratios of 27:1 in phosphatidylcholine (PC) and 23:1 in phosphatidylethanolamine (PE). The dominant fatty acid in testes was docosapentaenoic acid (22 : 5n-6), comprising 15 and 24 % of PC and PE, respectively. This fatty acid was significantly lower in the ZD rats, whereas 18 : 2n-6 was higher compared with the rats in the other diet groups. These results demonstrate that severe Zn deficiency adversely affects sperm integrity and modulates testis fatty acid composition by interrupting essential fatty acid metabolism. This suggests that Zn deficiency-associated abnormal testicular function is perhaps preceded by altered membrane fatty acid composition, especially of a major fatty acid, 22 : 5n-6.

The Effect of Peripheral Administration of Zinc on Food Intake in Rats Fed Zn-adequate or Zn-deficient Diets

Zinc deficiency induces a striking reduction of food intake in animals. To elucidate the mechanisms for this effect, two studies were connectedly conducted to determine the effects of peripheral administration of zinc on food intake in rats fed the zinc-adequate or zinc-deficient diets for a 3-week period. In study 1, two groups of male Sprague-Dawley rats were provided diets made either adequate (ZA; 38.89 mg/kg) or deficient (ZD; 3.30 mg/kg) in zinc. In study 2, after feeding for 3 weeks, both ZA and ZD groups received intraperitoneal (IP) injection of zinc solution with three levels (0.5, 1.0, and 2.0 microg zinc/g body weight, respectively) and cumulative food intake at 0.5, 1, 2, 4, and 24 h, and plasma hormones concentrations were measured. The results in study 1 showed rats fed the ZD diets revealed symptoms of zinc deficiency, such as sparse and coarse hair, poor appetite, susceptibility to surroundings, lethargy, and small movements. Zinc concentrations in serum, femur, and skeletal muscle of rats fed the ZD diets declined by 26.58% (P < 0.01), 27.32% (P < 0.01), and 24.22% (P < 0.05), respectively, as compared with ZA control group. These findings demonstrated that rat models with zinc deficiency and zinc adequacy had been fully established. The results in study 2 showed that IP administration of zinc in both ZA and ZD rats did not influence food intake at each time points (P > 0.05), although zinc deficiency suppressed food intake. Plasma neuropeptide Y (NPY) was higher, but insulin and glucagon were lower in response to zinc deficiency or zinc administration by contrast with their respective controls (P < 0.05). Leptin, T3, and T4 concentrations were uniformly decreased (P < 0.05) in rats fed the ZD diets in contrast to ZA diets; however, no differences (P > 0.05) were observed during zinc injection. Calcitonin gene-related peptide was unaffected (P > 0.05) by either zinc deficiency or zinc administration. The present studies suggested that zinc administration did not affect short-term food intake in rats even in the zinc-deficient ones; the reduced food intake induced by zinc deficiency was probably associated with the depression in thyroid hormones. The results also indicated that NPY and insulin varied conversely during the control of food intake.

Effects of Zinc on Hepatic Antioxidant Systems and the mRNA Expression Levels Assayed by cDNA Microarrays in Rats

Background: This study evaluated effects of zinc on the hepatic lipid peroxidation, antioxidant components and mRNA expression levels in rats. Methods: Three diets with different Zn levels including Zn adequacy (ZA; 34.50 mg/kg, control), Zn deficiency (ZD; 3.30 mg/kg), and Zn overdose (ZO; 345.45 mg/kg) were fed to rats for 6 weeks. The mRNA expression levels were analyzed by cDNA microarrays. Results: The body weight of rats fed the ZD diet was less (p < 0.01) than that of rats fed the ZA diet. Zn overdose elevated body weight, but the increase was not detected (p > 0.05) at week 6. Although copper and iron status in serum were declined (p < 0.01), those in liver were not affected (p > 0.05) by the high intake of zinc. The glutathione peroxidase (GPx) and glutathione (GSH) remained unchanged (p > 0.05) by zinc treatment. Rats fed the ZD diet showed reductions(p < 0.01) in the Cu-Zn superoxide dismutase (Cu-Zn SOD) and catalase (CAT) activity, and increases (p < 0.01) in the malondialdehyde and hydrogen peroxide (H₂O₂) contents. Rats fed the ZO diet particularly had higher Cu-Zn SOD (p < 0.01) activity. The mRNA expression levels of SOD were upregulated in the ZO group, and CAT was downregulated in the ZD group, while no changes in GPx mRNA levels were found after zinc treatment. Conclusion: The study suggested that zinc deficiency largely decreased body weight; zinc overdose, however, moderately stimulated growth in the early growing phase of rats. High dietary zinc did not compete with liver copper and iron status. Although Zn deficiency impaired antioxidant functions, zinc overdose hardly enhanced the antioxidant systems of animals.

Zinc-deficient rats have more limited bone recovery during repletion than diet-restricted rats.

The objective of this study was to investigate the effects of dietary zinc deficiency and diet restriction on bone development in growing rats, and to determine whether any adverse effects could be reversed by dietary repletion. Weanling rats were fed either a zinc-deficient diet ad libitum (ZD; <1 mg zinc/kg) or nutritionally complete diet (30 mg zinc/kg) either ad libitum (CTL) or pair-fed to the intake of the ZD group (DR; diet-restricted) for 3 weeks (deficiency phase) and then all groups were fed the zinc-adequate diet ad libitum for 3, 7, or 23 days (repletion phase). Excised femurs were analyzed for bone mineral density (BMD) using dual-energy x-ray absorptiometry, and plasma was analyzed for markers of bone formation (osteocalcin) and resorption (Ratlaps). After the deficiency phase, ZD had lower body weight and reduced femur BMD, zinc, and phosphorus concentrations compared with DR; and these parameters were lower in DR compared with CTL. Femur calcium concentrations were unchanged among the groups. Reduced plasma osteocalcin in ZD and elevated plasma Ratlaps in DR suggested that zinc deficiency limits bone formation while diet restriction accelerates bone resorption activity. After 23 days of repletion, femur size, BMD, and zinc concentrations remained lower in ZD compared with DR and CTL. Body weight and femur phosphorus concentrations remained lower in both ZD and DR compared with CTL after repletion. There were no differences in plasma osteocalcin concentrations after the repletion phase, but the plasma Ratlaps concentrations remained elevated in DR compared with CTL. In summary, both ZD and DR lead to osteopenia during rapid growth, but the mechanisms appear to be due to reduced modeling in ZD and higher turnover in DR. Zinc deficiency was associated with a greater impairment in bone development than diet restriction, and both deficiencies limited bone recovery during repletion in growing rats.

Effects of dietary fat and zinc on adiposity, serum leptin and adipose fatty acid composition in C57BL/6J mice

Zinc (Zn) has been implicated in altered adipose metabolism, insulin resistance and obesity. The objective of this study was to investigate the effects dietary Zn deficiency and supplementation on adiposity, serum leptin and fatty acid composition of adipose triglycerides and phospholipid in C57BL/6J mice fed low-fat (LF) or high-fat (HF) diets for a 16 week period. Weanling C57BL/6J mice were fed LF (16% kcal from soybean oil) or HF (39% kcal from lard and 16% kcal from soybean oil) diets containing 3, 30 or 150 mg Zn/kg diet (ZD = Zn-deficient, ZC = Zn control and ZS = Zn-supplemented, respectively). HF-fed mice had higher fat pad weights and lower adipose Zn concentrations than the LF-fed mice. The ZD and ZS groups had a reduced content of fatty acids in adipose triglycerides compared to the ZC group, suggesting that zinc status may influence fatty acid accumulation in adipose tissue. Serum leptin concentration was positively correlated with body weight and body fat, and negatively correlated with adipose Zn concentration. Dietary fat, but not dietary Zn, altered the fatty acid composition of adipose tissue phospholipid and triglyceride despite differences in Zn status assessed by femur Zn concentrations. The fatty acid profile of adipose triglycerides generally reflected the diets. HF-fed mice had a higher percentage of C20:4 n-6, elevated ratio of n-6/n-3, lower ratio of PUFA/SAT and reduced percentage of total n-3 fatty acids in adipose phospholipid, a fatty acid profile associated with obesity-induced risks for insulin resistance and impaired glucose transport. In summary, the reduced adipose Zn concentrations in HF-fed mice and the negative correlation between serum leptin and adipose Zn concentrations support an interrelationship among obesity, leptin and Zn metabolism.

Inanition may Reduce Alkaline Phosphatase Activity in Liver and Intestine of Zinc-Deficient Mice

Zinc-deficiency was induced in mice by feeding a Zn-deficient basal diet (ZD dietary group) containing 9% lipid (6% corn oil, 3% cod liver oil) for 8 wk. Thereafter, the corn oil was withdrawn from the basal diet and a subset of Zn-deficient animals (ZDLR group) was fed this modified low fat diet for another 8 wk. Alkaline phosphatase activity in intestine and liver was compared in these mice and in those allowed ad libitum access to the lipid-adequate Zn-supplemented diet (ZS group), in those pair-fed the Zn-supplemented diet (PF group) and in those fed the lipid-adequate, Zn-deficient diet ad libitum (ZD group). The enzyme activity in both intestine and liver of the ZDLR group was greater than in those of the ZD group and greater than or equal to those of the ZS and PF diet groups. The results of this study suggest that the reduction in alkaline phosphatase in Zn-deficient animals is a response secondary to associated inanition.

Effect of marginal zinc deficiency on the apolipoprotein-B content and size of mesenteric lymph chylomicrons in adult rats.

To investigate the mechanisms underlining the impaired intestinal absorption of lipids in zinc deficiency, the apo-B content and chemical composition of chylomicrons from marginally zinc-deficient rats fed 2.8 ppm of dietary zinc (ZD) were compared with those from pair-fed (PF) and ad libitum control (CT) groups fed an adequate level (30.8 ppm) of zinc. Chylomicrons, obtained by cannulating the mesenteric lymph, were isolated by ultracentrifugation at 1.3 X 10(6) g/min at 12 C and purified by 2% agarose column chromatography. Apolipoprotein- (apo) B was separated by the method of isopropanol precipitation. The apo-B concentration of chylomicrons was lowered significantly in ZD group. The apo-B contents of chylomicrons in ZD, PF and CT rats, as expressed as % chylomicron protein, were 8.7 +/- 0.1, 11.5 +/- 0.5 and 10.7 +/- 0.7%, respectively. No significant differences were noted between ZD and PF groups in total protein (TP), phospholipid (PL), triglyceride (TG) and cholesterol (CH), although there was a slight decrease in TG and an increase in CH in CT rats compared with ZD and PF groups. The ratio of the core to surface constituents, as determined by TG/(TP + PL), was significantly higher in ZD group relative to the controls, suggesting that chylomicrons from ZD rats were larger. This finding was consistent with the appearance of larger chylomicron particles in the lacteal of the intestinal mucosa following lipid ingestion. These findings suggest that the intestinal synthesis of apo-B may be defective in zinc-deficient rats and may explain in part the impaired absorption of dietary lipids observed in zinc deficiency.

Effects of Isolated Zinc Deficiency on the Composition of Skeletal Muscle, Liver and Bone during Growth in Rats

We investigated the effects of zinc deficiency on body composition by using intragastric force-feeding to obviate decreased food intake and altered eating patterns. Weanling male Sprague-Dawley rats were fed a purified zinc-deficient diet: the ad libitum-fed control group (AL; eight rats) was given powdered diet and water containing 25 ppm zinc; the zinc-replete group (ZN; nine rats) was force-fed a diet blended with water containing zinc in an amount of equal caloric intake to the AL group and allowed access to water containing zinc. The zinc intake of ZN rats was approximately twice that of AL rats based on water intake. The zinc-deficient group (ZD; 13 rats) was fed similarly to the ZN group except deionized water was used for diet preparation and drinking water. After 8 d, body and muscle weight were lower in the ZD group than in the ZN group. Femur weights were similar in the two groups. Serum, liver and femur zinc concentrations were 85, 22 and 42% lower, respectively, in the ZD group than in the ZN group. Serum glucose, relative liver weight, liver glycogen and liver lipids were higher, but muscle and liver DNA were lower in the ZD group than in control groups.

Learning and memory disabilities in young adult rats from mildly zinc deficient dams

Three experiments were conducted to test the behavior of the offspring of rat dams (ZD) fed a mildly zinc deficient diet (10.0 μg Zn/g) during pregnancy and lactation. Since zinc deficiency causes anorexia, a second group of rat dams (PF) was fed the same quantity of the diet during gestation and lactation as was consumed by their ZD mates. A third group of rats (AL) was fed the diet ad lib during gestation and lactation. The PF and AL dams were given zinc supplemented (25.0 μg Zn/ml) drinking water whereas the ZD dams were given double distilled, deionized drinking water. After weaning, the offspring of all dams were fed Purina Laboratory Chow ad lib until they were 100 days old. The offspring were then reduced to 85% of their ad lib weight and tested on a 17-arm radial maze for memory and learning. In Experiments 1 and 2, the ZD males suffered a significant learning deficit when compared to the AL males. Whereas the PF males suffered a significant learning impairment in Experiment 1, the learning deficit of the PF group was not as severe as the deficit of the ZD group. There was no impairment in reference (long-term) memory for any of the groups. In Experiment 3, significant differences in working (short-term) memory were found among the three groups of females. The ZD group was significantly inferior in working memory when compared to the PF and AL groups. No significant differences in working memory were found between the PF and AL groups.

Effects of short-term isolated zinc deficiency on intestinal growth and activities of several brush border enzymes in weaning rats.

To determine whether zinc has a specific role on intestinal growth and function, three groups of male weanling Sprague-Dawley rats were fed a semipurified zinc-deficient diet: ad libitum fed group received powdered diet and water containing 25 ppm of zinc; force fed (ZN, ZD) groups were fed identical amounts of diet to the ad libitum fed group by intragastric infusion three times per day. The diets were aqueous suspensions made with either deionized water (ZD) or water containing 25 ppm of zinc (ZN), and additional drinking water with (ZN) or without zinc (ZD) was offered ad libitum. Rats were sacrificed after 8 days of feeding. The ZD group showed growth arrest, perioral and periorbital dermal lesions, and abdominal distention within 8 days of feeding. Mucosal DNA, protein, sucrase, maltase, lactase, leucine aminopeptidase, and alkaline phosphatase were significantly decreased in the ZD group, whereas intestinal length, weight, and mucosal weight were unaltered. These results suggest that short-term isolated zinc deficiency impairs growth, digestion, and absorption in the rat small intestine, even in the absence of associated protein calorie malnutrition.

Studies of marginal zinc deprivation In rhesus monkeys: II. Pregnancy outcome

A marginal state of zinc deficiency was induced in the pregnant nonhuman primate, Macaca mulatta, by feeding a diet containing 4 ppm zinc beginning at conception. Pregnancy outcome of marginally zinc-deficient monkeys (ZD) was compared to both pair-fed (PF) and ad libitum fed (AL) control animals (100 ppm zinc). Stillbirths, abortions, and delivery complications were more frequent in both ZD and PF dams than in AL controls; no malformations were detected (maternal plasma zinc was normal during organogenesis). Male ZD neonates weighed significantly less than same sex controls; also, in relation to colony norms, 7/8 ZD males, 2/8 ZD females, and 1/10 PF controls were of low birth weight. Further, plasma zinc and iron levels were lower in ZD neonates than in AL and PF controls. ZD neonates also had reduced muscle tonus. Birth weight and maternal plasma zinc concentration were negatively correlated in ZD group but positively correlated in AL and PF groups. Indeed, maternal plasma zinc concentration alone did not identify a state of zinc deficiency which impaired fetal growth in monkeys.

Zinc Deficiency Affects neither Platelet Arachidonic Acid Metabolism nor Platelet Aggregation in Rats

The effects of zinc deficiency on arachidonic acid (AA) metabolism and platelet aggregation were studied in rats. Concentrations of AA metabolites synthesized by collagen-stimulated platelets were greater in rats fed a zinc-deficient diet (ZD group) than pair-fed control rats (PF group). This difference appeared to be due to increased platelet number in the ZD group. Preincubation of platelet-rich plasma of ZD group with various concentrations of zinc sulfate, prior to the aggregation induced by collagen suspension, affected neither concentrations of AA metabolites nor the degree of platelet aggregation. Contrary to a report by other investigators, ADP-induced platelet aggregation was not impaired in rats fed the zinc-deficient diet for 1 week or 5 weeks as compared to the pair-fed controls. Secondary phase aggregation was not observed during ADP-induced platelet aggregation regardless of concentrations of ADP, types and concentrations of anticoagulants used, routes of blood collection or types of dietary protein in this study. These results indicated that zinc deficiency does not seem to affect arachidonic acid metabolism or platelet aggregation in rats in relatively short-term studies.

Mild Zinc Deficiency and Undernutrition During the Prenatal and Postnatal Periods in Rats: Effects on Weight, Food Consumption, and Brain Catecholamine Concentrations

Rat dams were fed a 20% sprayed egg white diet, containing 10 ppm zinc, during gestation and lactation (ZD) and compared to zinc-adequate pair-fed (PF) and ad libitum fed (AL) control animals. AL dams consumed more food than the ZD group. Throughout gestation AL dams were heavier than PF and ZD dams. During lactation AL dams were heavier than the ZD dams which in turn were heavier than PF dams. Birth weights of ZD pups were less than the PF and AL pups. Postnatal daily weight gains of ZD pups were less than the PF pups which were less than AL pups. After weaning ZD pups fed commercial rat food gained less weight than PF and AL pups, and weight gain of PF and AL pups was similar. ZD dams had lower plasma zinc than control dams at parturition and at the end of lactation. Femur zinc of ZD, PF and AL dams was similar at parturition. ZD dams had lower femur zinc than PF and AL dams after lactation. Femur and liver zinc of ZD pups was lower than in PF and AL pups at birth. Regional brain catecholamine levels were not measured, but whole brain concentrations of catecholamines were not different among the groups. Thus, while mild zinc deficiency adversely affected growth of pups, effects on brain remain to be identified.zinc deficiency food intake weight change brain catecholamines