Maternal Zinc Deficiency Research Articles

Intergenerational Impact of Parental Zinc Deficiency on Metabolic and Redox Outcomes in Drosophila melanogaster.

Zinc deficiency is a common nutritional disorder with detrimental health consequences. Whether parental zinc deficiency induces intergenerational effects remains largely unknown. We investigated the effects of a combined maternal and paternal zinc deficiency on offspring's metabolic outcomes and gene expression changes in Drosophila melanogaster. The parent flies were raised on zinc-deficient diets throughout development, and their progeny were assessed. Offspring from zinc-deprived parents exhibited a significant (p < 0.05) increase in body weight and whole-body zinc levels. They also displayed disrupted glucose metabolism, altered lipid homeostasis, and diminished activity of antioxidant enzymes. Gene expression analysis revealed significant (p < 0.05) alterations in zinc transport genes, with increases in mRNA levels of dZIP1 and dZnT1 for female and male offspring, respectively. Both sexes exhibited reduced dZnT35C mRNA levels and significant (p < 0.05) increases in the mRNA levels of DILP2 and proinflammatory markers, Eiger and UPD2. Overall, female offspring showed higher sensitivity to parental zinc deficiency. Our findings underscore zinc's crucial role in maintaining health and the gender-specific responses to zinc deficiency. There is the need for further exploration of the underlying mechanisms behind these intergenerational effects.

Maternal Fed Zinc-Deficient Diet: Effects on Relaxin Family Peptides and Oxidant System in the Testis and Liver Tissue of Male Offspring

Today, the studies are limited on roles of insulin-like peptide 3 (INSL3), insulin-like peptide 7 (INSL7), and relaxin family peptide receptor 1 (RXFP1) which are synthesized by the testis. It is aimed to investigate the levels of the sex hormone as testosterone and the family of insulin-like proteins (relaxin family peptides), which are important in the puberty transition, in the testicular and liver tissues of male offspring born to female rats fed a zinc-deficient diet during the pregnancy, and in the changes in lipid peroxidation markers. The study was performed on 40 male offspring. In Group I: Control group, both male offspring and mothers were fed with standard rat chow. In Group II: Zinc deficient diet, both male offspring and mothers were fed a zinc-deficient diet (2.8 mg/kg zinc). In Group III: Normal diet, male offspring fed standard rat chow for 45 days (66th day) after being separated from their mothers with a maternal zinc-deficient diet. In Group IV: Zinc-supplemented diet, offspring fed with zinc supplemented (5 mg/kg/day intraperitoneal zinc sulfate, i.p.) in addition to standard rat chow after being separated from their mothers with maternal zinc deficiency until the termination of the study (66th day). Our study suggests that zinc-supplemented diets play an important role in the changes in INSL3, INSL7, RXFP1, and testosterone levels during spermatogenesis. INSL7, INSL3, and RXFP1 levels were higher in zinc-supplemented group than the zinc-deficient diet group. Liver levels of INSL3, INSL7, and MDA were significantly different in zinc-deficiency diet group than zinc-supplemented group.

Marginal Maternal Zinc Deficiency Produces Liver Damage and Altered Zinc Transporter Expression in Offspring Male Rats.

The aim of this study was to investigate how zinc deficiency and supplementation affect liver markers including autotaxin, kallistatin, endocan, and zinc carrier proteins ZIP14 and ZnT9 in rats exposed to maternal zinc deficiency. Additionally, the study aimed to assess liver tissue damage through histological examination. A total of forty male pups were included in the research, with thirty originating from mothers who were given a zinc-deficient diet (Groups 1, 2, and 3), and the remaining ten born to mothers fed a standard diet (Group 4). Subsequently, Group 1 was subjected to a zinc-deficient diet, Group 2 received a standard diet, Group 3 received zinc supplementation, and Group 4 served as the control group without any supplementation. Upon completion of the experimental phases of the study, all animals were sacrificed under general anesthesia, and samples of liver tissue were obtained. The levels of autotaxin, kallistatin, endocan, ZIP 14, and ZnT9 in these liver tissue samples were determined using the ELISA technique. In addition, histological examination was performed to evaluate tissue damage in the liver samples. In the group experiencing zinc deficiency, both endocan and autotaxin levels increased compared to the control group. With zinc supplementation, the levels of endocan and autotaxin returned to the values observed in the control group. Similarly, the suppressed levels of kallistatin, ZIP14, and ZnT9 observed in the zinc deficiency group were reversed with zinc supplementation. Likewise, the reduced levels of kallistatin, ZIP14, and ZnT9 seen in the zinc deficiency group were rectified with zinc supplementation. Moreover, the application of zinc partially ameliorated the heightened liver tissue damage triggered by zinc deficiency. This study is the pioneering one to demonstrate that liver tissue dysfunction induced by a marginal zinc-deficient diet in rats with marginal maternal zinc deficiency can be alleviated through zinc supplementation.

The relationship between beta cell activation and SLC30A8/ZnT8 levels of the endocrine pancreas and maternal zinc deficiency in rats

ObjectivesZinc, which is found in high concentrations in the β-cells of the pancreas, is also a critical component for the endocrine functions of the pancreas. SLC30A8/ZnT8 is the carrier protein responsible for the transport of zinc from the cytoplasm to the insulin granules. The aim of this study was to investigate how dietary zinc status affects pancreatic beta cell activation and ZnT8 levels in infant male rats born to zinc-deficient mothers. MethodsThe study was performed on male pups born to mothers fed a zinc-deficient diet. A total of 40 male rats were divided into 4 equal groups. Group 1: In addition to maternal zinc deficiency, this group was fed a zinc-deficient diet. Group 2: In addition to maternal zinc deficiency, this group was fed a standard diet. Group 3: In addition to maternal zinc deficiency, this group was fed a standard diet and received additional zinc supplementation. Group 4: Control group. Pancreas ZnT8 levels were determined by ELISA method and insulin-positive cell ratios in β-cells by immunohistochemistry. ResultsThe highest pancreatic ZnT8 levels and anti-insulin positive cell ratios in the current study were obtained in Group 3 and Group 4. In our study, the lowest pancreatic ZnT8 levels were obtained in Group 1 and Group 2, and the lowest pancreatic anti-insulin positive cell ratios were obtained in Group 1. ConclusionThe results of the present study; in rats fed a zinc-deficient diet after maternal zinc deficiency has been established shows that ZnT8 levels and anti-insulin positive cell ratios in pancreatic tissue, which is significantly suppressed, reach control values with intraperitoneal zinc supplementation.

S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis

Autism Spectrum Disorders (ASD) are caused by a combination of genetic predisposition and nongenetic factors. Among the nongenetic factors, maternal immune system activation and zinc deficiency have been proposed. Intriguingly, as a genetic factor, copy-number variations in S100B, a pro-inflammatory damage-associated molecular pattern (DAMP), have been associated with ASD, and increased serum S100B has been found in ASD. Interestingly, it has been shown that increased S100B levels affect zinc homeostasis in vitro. Thus, here, we investigated the influence of increased S100B levels in vitro and in vivo during pregnancy in mice regarding zinc availability, the zinc-sensitive SHANK protein networks associated with ASD, and behavioral outcomes. We observed that S100B affects the synaptic SHANK2 and SHANK3 levels in a zinc-dependent manner, especially early in neuronal development. Animals exposed to high S100B levels in utero similarly show reduced levels of free zinc and SHANK2 in the brain. On the behavioral level, these mice display hyperactivity, increased stereotypic and abnormal social behaviors, and cognitive impairment. Pro-inflammatory factors and zinc-signaling alterations converge on the synaptic level revealing a common pathomechanism that may mechanistically explain a large share of ASD cases.

The effects of maternal zinc deficiency on myometrial contractility: an in vitro study

Aim: The aim of the study is to investigate the effects of zinc-supplemented or zinc-deficient diet on myometrial contractility during pregnancy. Material and Method: The patients were divided in four groups as Group 1 (n=5) fed with zinc-deficient diet, Group 2 (n=5) fed with zinc-supplemented diet, Group 3 (n=5) fed with normal diet, and Group 4 (n=5) as the control group and in vitro contractility study was conducted in the myometrial samples taken from these four groups, and intergroup comparison was performed for the results. The p&lt;0.05 was accepted as significant. Results: In the evaluation of the contractility data, it was determined that the strength and period of contraction and also the frequencies increased in the zinc-supplemented group compared to the other groups. The difference was found to be significant only in frequency ( p&lt;0.05). In the intergroup comparison, the frequency was found to be significantly higher in the zinc-supplemented group than all the other groups ( p&lt;0.05). Conclusion: This in vitro finding can indicate the importance of zinc supplementation during pregnancy for postpartum bleeding.

Comparison of maternal serum and neonatal cord blood levels of zinc in relation to birth weight and period of gestation

Background: Women are at increased risk of zinc deficiency during pregnancy because of high fetal requirements for zinc. Severe maternal zinc deficiency has been associated with poor fetal growth, spontaneous abortion and congenital malformations (i.e., anencephaly), whereas milder forms of zinc deficiency have been associated with low birth weight (LBW), intrauterine growth retardation, and preterm delivery. However, the research relating maternal zinc status and birth weight has not produced consistent results. This study has been undertaken to confirm the association between maternal serum zinc concentration and birth weight and period of gestation in setting like India.Methods: A total of 100 new-borns were included and divided into two groups, the ‘study group’ had babies with birth weight &lt;2.5 kg and control group’ with babies &gt;2.5 kg birth weight. Cord blood from the new-borns and serum samples of mothers were collected and the zinc levels were measured.Results: The correlation of cord blood and the maternal serum zinc levels were assessed in relation to birth weight and the gestational age. The results were compared between the two groups. The difference in values between the two groups was statistically significant, maternal serum zinc levels and birth weight (84.78±21.62 vs 66.04±18.66) (‘P’ value 0.04), cord blood zinc levels and birth weight (98.44±22.59 vs 79.78±19.54) (‘P’ value &lt;0.001). The maternal serum and cord blood zinc was compared between the preterm and term; the results were statistically significant.Conclusions: The maternal and cord blood levels of zinc are correlated well with the birth weight and the gestational age at delivery. Supplementation of zinc during gestation might help reduce the incidence of IUGR and the risk of prematurity.

Gestational zinc deficiency impairs brain astrogliogenesis in rats through multistep alterations of the JAK/STAT3 signaling pathway

We previously showed that zinc (Zn) deficiency affects the STAT3 signaling pathway in part through redox-regulated mechanisms. Given that STAT3 is central to the process of astrogliogenesis, this study investigated the consequences of maternal marginal Zn deficiency on the developmental timing and key mechanisms of STAT3 activation, and its consequences on astrogliogenesis in the offspring. This work characterized the temporal profile of cortical STAT3 activation from the mid embryonic stage up to young adulthood in the offspring from dams fed a marginal Zn deficient diet (MZD) throughout gestation and until postnatal day (P) 2. All rats were fed a Zn sufficient diet (control) from P2 until P56. Maternal zinc deficiency disrupted cortical STAT3 activation at E19 and P2. This was accompanied by altered activation of JAK2 kinase due to changes in PTP1B phosphatase activity. The underlying mechanisms mediating the adverse impact of a decreased Zn availability on STAT3 activation in the offspring brain include: (i) impaired PTP1B degradation via the ubiquitin/proteasome pathway; (ii) tubulin oxidation, associated decreased interactions with STAT3 and consequent impaired nuclear translocation; and (iii) decreased nuclear STAT3 acetylation. Zn deficiency-associated decreased STAT3 activation adversely impacted astrogliogenesis, leading to a lower astrocyte number in the early postnatal and adult brain cortex. Thus, a decreased availability of Zn during early development can have a major and irreversible adverse effect on astrogliogenesis, in part via multistep alterations in the STAT3 pathway.

Effect of Maternal Marginal Zinc Deficiency on Development, Redox Status, and Gene Expression Related to Oxidation and Apoptosis in an Avian Embryo Model.

Maternal severe zinc (Zn) deficiency resulted in growth retardation and high mortality during embryonic development in human. Therefore, this study is aimed at evaluating the effect of maternal marginal Zn deficiency on the development and redox status to avoid severe Zn deficiency using an avian model. A total of 324 laying duck breeders at 214 days old were randomly allotted into 3 dietary Zn levels with 6 replicates of 18 ducks per replicate. The birds were fed experimental diets including 3 dietary supplemental Zn levels of 0 mg/kg (maternal Zn-deficient group, 29.2 mg Zn/kg diet), 60 mg/kg (maternal Zn-adequate group), and 120 mg/kg (maternal Zn-high group) for 6 weeks. Dietary Zn levels had on effect on egg production and fertility (P > 0.05), whereas dietary Zn deficiency decreased breeder plasma Zn concentration and erythrocytic alkaline phosphatase activity at week 6 and inhibited erythrocytic 5′-nucleotidase (5′-NT) activity at weeks 2, 4, and 6 (P < 0.05), indicating that marginal Zn-deficient status occurred after Zn depletion. Maternal marginal Zn deficiency increased embryonic mortality and contents of superoxide anion radical, MDA, and PPC and reduced MT content and CuZnSOD activity in duck embryonic livers on E29. The MDA content was positively correlated with embryonic mortality. Maternal marginal Zn deficiency increased BCL2-associated X protein and Caspase-9 mRNA expressions as well as decreased B-cell lymphoma-2 and MT1 mRNA and signal AKT1 and ERK1 protein expressions (P < 0.05). Breeder plasma Zn concentration and erythrocytic 5′-NT activities at week 6 were positively correlated with GSH-Px activity and GPx, MT1, and BCL2 mRNA expressions in embryonic livers on E29. In conclusion, erythrocytic 5′-NT activity could be more rapid and reliable to monitor marginal Zn-deficient status. Marginal Zn deficiency impaired hatchability and antioxidant defense system and then induced oxidative damage and apoptosis in the embryonic liver, contributing to the greater loss of duck embryonic death.

Effects of early-life zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns

ABSTRACT Objective To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns. Methods Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected. Cognitive ability of offspring at P21 and P60 were determined by Morris water maze. The expression of proteins including DNMT3a, DNMT1, GADD45β, MeCP2 and BDNF in the offspring hippocampus were detected by Western-blot. The methylation status of BDNF promoter region in hippocampus of offspring rats was detected by MS-qPCR. Results Compared with the ZA and PF groups, pups in the ZD group had lower zinc levels and AKP activity in the serum, spent more time finding the platform and spent less time going through the platform area. Protein expression of DNMT1 and GADD45b were downregulated in the ZD group during P0 and P21 but not P60 compared with the ZA and PF group, these results were consistent with a reduction in BDNF protein at P0 (neonate), P21. However, when pups of rats in the ZD group were supplemented with zinc ion from P21 to P60, MeCP2 and GADD45b expression were significantly downregulated compared with the ZA and PF group. Conclusion Post-weaning zinc supplementation may improve cognitive impairment induced by early life zinc deficiency, whereas it may not completely reverse the abnormal expression of particular genes that are involved in DNA methylation, binding to methylated DNA and neurogenesis.

Assessment of Zinc Status Among Pregnant Women Attending a Tertiary Level Hospital of Sunsari District, Nepal

Zinc deficiency is one of the major public health problems especially in developing countries, with an estimation of over 80% of pregnant women to be zinc deficient worldwide. Maternal zinc deficiency elevates the risk of foetal growth restriction. This study aimed to assess zinc deficiency and to examine the factors associated with zinc status among pregnant women attending a tertiary level hospital in Sunsari district, province no. one, Nepal. Pregnant women were selected by using time frame consecutive sampling at B. P. Koirala Institute of Health Sciences, Dharan from September to November 2018. Data on nutritional, socio-demographic and reproductive profiles were collected using a semi-structured questionnaire. Blood was collected from each pregnant woman to estimate serum zinc concentration by atomic absorption spectrophotometry. Association between serum zinc concentration and predictor variables were assessed using chi-square test. A total of 156 women participated in the study. The prevalence of zinc deficiency among the pregnant women was 22.6%. Our data did not show association of any of the socio-demographic, nutritional and reproductive variables with serum zinc status (p-value>0.05) in chi-square. Zinc deficiency was found to be prevalent in our targeted population. However, community based studies need to be conducted for exploring more precise relationship between zinc status and other variables.

Dietary zinc deficiency or supplementation during gestation increases breast cancer susceptibility in adult female mice offspring following a J-shaped pattern and through distinct mechanisms

Zinc is required for fetal development and is involved in key processes associated with breast carcinogenesis. We evaluated whether maternal zinc deficiency or supplementation during gestation influences female offspring susceptibility to breast cancer in adulthood. C57BL/6 mice consumed during gestation control (30 p.p.m. zinc), zinc-deficient (8 p.p.m) or zinc-supplemented (45 p.p.m.) diets. Maternal zinc supplementation increased in female mice offspring the incidence of chemically-induced mammary adenocarcinomas that were heavier, compared to control group. This was accompanied by a decreased number of terminal end buds, increased cell proliferation and apoptosis, and increased tumor suppressors p21, p53 and Rassf1, Zfp382 and Stat3 expression in mammary glands, as well as increased zinc status. Although maternal zinc deficiency did not alter the incidence of these lesions, it also induced heavier mammary adenocarcinomas, compared to control group. These effects were accompanied by a decreased number of terminal end buds, increased proto-oncogenes c-Myc and Lmo4 expression and H3K9Me3 and H4K20Me3 epigenetic marks in mammary glands of offspring, and decreased zinc status and increased levels of oxidative marker malondialdehyde. The data suggest that both maternal zinc deficiency and supplementation during gestation programmed increased breast cancer susceptibility in adult mice offspring following a J-shaped pattern through distinct mechanisms.

Zinc Intake in Lactating Mothers in Jakarta

Background :Maternal zinc deficiency may cause hindrance in breast milk ejection and low zinc content in breast milk. This may cause zinc deficiency in babies. Therefore, adequate zinc intake is crucial to maternal and baby’s health. Food source of zinc are mainly protein rich foods. High intake of fiber may decrease zinc bioavailability as they usually contain phytate. Objective :This study aimed to profile zinc, total protein, and fiber intake among lactating mother in Jakarta. Methods :This was a cross sectional study conducted in Grogol Petamburan Public Health Center, West Jakarta and Cilincing Public Health Center, North Jakarta between February and April 2019. Consecutive sampling method was used to recruit 95 lactating mothers aged 20-35 who were nursing 1-6 months old babies. Basic characteristic data such as socioeconomic level and education level was collected during interview process. Semi questionnaire food frequency questionnaire was used to gain zinc intake data and 24 hours food recall was used to gain protein and fiber intake data. Results :The prevalence of zinc deficiency in Jakarta was 76.8% although 56% had taken enough daily protein. 99% of the samples had low fiber intake. Around 47% of subjects have monthly income lower than regional minimum wage and 68% of the samples has middle level of education. Conclusion :Zinc intake among maternal diet in Jakarta is below the recommendation although more than half of the samples had taken enough daily protein and very low fiber. The protein intake must furthermore be specialized into animal and vegetable protein to increase the accuracy of the data. A specialized education about the importance of zinc for maternal health and food sources of zinc must be conducted among lactating woman. The need of zinc supplementation might be considered.

Early Developmental Marginal Zinc Deficiency Affects Neurogenesis Decreasing Neuronal Number and Altering Neuronal Specification in the Adult Rat Brain.

During pregnancy, a decreased availability of zinc to the fetus can disrupt the development of the central nervous system leading to defects ranging from severe malformations to subtle neurological and cognitive effects. We previously found that marginal zinc deficiency down-regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and affects neural progenitor cell (NPC) proliferation. This study investigated if marginal zinc deficiency during gestation in rats could disrupt fetal neurogenesis and affect the number and specification of neurons in the adult offspring brain cortex. Rats were fed a marginal zinc deficient or adequate diet throughout gestation and until postnatal day (P) 2, and subsequently the zinc adequate diet until P56. Neurogenesis was evaluated in the offspring at embryonic day (E)14, E19, P2, and P56 measuring parameters of NPC proliferation and differentiation by Western blot and/or immunofluorescence. At E14 and E19, major signals (i.e., ERK1/2, Sox2, and Pax6) that stimulate NPC proliferation and self-renewal were markedly downregulated in the marginal zinc deficient fetal brain. These alterations were associated to a lower number of Ki67 positive cells in the ventricular (VZs) and subventricular zones (SVZs). Following the progression of NPCs into intermediate progenitor cells (IPCs) and into neurons, Pax6, Tbr2 and Tbr1 were affected in the corresponding areas of the brain at E19 and P2. The above signaling alterations led to a lower density of neurons and a selective decrease of glutamatergic neurons in the young adult brain cortex exposed to maternal marginal zinc deficiency from E14 to P2. Current results supports the concept that marginal zinc deficiency during fetal development can disrupt neurogenesis and alter cortical structure potentially leading to irreversible neurobehavioral impairments later in life.

Maternal zinc metabolism and changes of metallothionein-1 and zinc transporter-1 in fetal congenital heart diseases

Objective To investigate maternal zinc metabolism and the changes of zinc-related factors as metallothionein-1(MT1) and zinc transporter-1(ZnT1) in certain types of congenital heart diseases (CHD). Methods Fifteen infants with interventricular septal defect, 12 infants with atrial septal defect and 7 infants with tetralogy of Fallot, together with their mothers were enrolled, and normal infants and their mothers were enrolled by a ratio of 1∶1 with the above three types of CHD diseases. General conditions of the mothers, along with their diets and zinc-containing drug supplementation during the pregnancy, were surveyed. Maternal blood zinc levels and serum alkaline phosphatase activities at gestation week 32 and delivery or induced abortion, and the protein and mRNA expressions of MT1 and ZnT1 in maternal serum and placental tissue at delivery or induced abortion were assayed. Results The general conditions were comparable between the CHD group and control group. The ratio of the mothers taking more zinc-rich food was significantly lower in the CHD group than in the control group. Circulating zinc levels in interventricular septal defect (73.55±5.79 μmol/L), atrial septal defect (72.66±5.82 μmol/L) and tetralogy of Fallot (68.72±6.72 μmol/L) groups were significantly lower than those in the control groups (82.77±7.88, 84.58±7.55 and 85.66±7.30 μmol/L) at delivery (P all <0.05). Similar change patterns were seen for serum alkaline phosphatase activities. The relative quantities of serum MT1 and ZnT1 proteins in interventricular septal defect (73.22±36.54 and 68.55±27.82), atrial septal defect (64.29±38.26 and 74.55±29.67) and tetralogy of Fallot (67.88±30.50 and 70.13±29.65) groups were significantly lower than those in their corresponding control groups (166.31±67.43 and 97.67±30.22, 182.56±71.40 and 111.65±32.70, and 173.81±62.36 and 108.27±28.52, P<0.01 or P<0.05). The relative quantities of placental MT1 and ZnT1 proteins and mRNA expressions in interventricular septal defect (protein quantities 0.438±0.096 and 0.384±0.061, mRNA expressions 1.23±0.82 and 0.96±0.39), atrial septal defect (0.427±0.093 and 0.377±0.059, 1.17±0.70 and 0.85±0.40) and tetralogy of Fallot (0.414±0.111 and 0.336±0.066, 1.31±0.97 and 0.90±0.38) groups were significantly lower than those in their corresponding control groups (protein quantities 0.565±0.083 and 0.541±0.090, mRNA expressions 2.78±1.06 and 1.67±0.33; protein quantities 0.622±0.136 and 0.493±0.079, mRNA expressions 2.85±0.89 and 1.72±0.38; protein quantities 0.637±0.125 and 0.521±0.089, mRNA expressions 3.21±0.99 and 1.61±0.29; P<0.01 or P<0.05). Conclusion Mothers with their fetus of certain types of CHD are found zinc deficiency, and down-regulation of MT1 and ZnT1 expressions in the serum and placenta may involve in the pathogenesis of CHD when maternal zinc deficiency. Key words: Zinc deficiency; Congenital heart disease; Pregnancy; Metallothionein-1; Zinc transporter-1

The effects of zinc supplementation on inflammatory parameters in pregnant women with impaired glucose tolerance: a randomized placebo controlled clinical trial

Pregnancy is hyperglycemic cycle of life and usually associated with insulin resistance from mid- gestation. Previous studies indicate that abnormal production of some proteins secreted from adipocytes (adipokines) encloses in pathogenesis of insulin resistance and gestational diabetes mellitus (GDM). It is proven that maternal zinc deficiency affects glucose metabolism, but the interaction between zinc and adipokines secretion are not well understood. This study aims to evaluate the effect of zinc supplementation on Vaspin and IL-6 levels in pregnant women with impaired glucose tolerance (IGT). In this matched, placebo controlled double blind clinical trial, 46 pregnant women with impaired glucose tolerance were randomly distributed to zinc (n=23) and placebo (n=23) groups and received 30 mg/day zinc gluconate or placebo for eight regular weeks. The study was conducted in Shabestar district, North West of Iran. Serum Vaspin and IL-6 levels were assessed before and after intervention. There was a significant decrease in Vaspin and IL-6 levels in zinc group (p= 0.004, p= 0.034, respectively). Further, changes in fasting Vaspin levels had a positive correlation with change in fasting IL-6 levels in both zinc (r= + 0.820, p<0.001) and placebo (r= + 1.000, p<0.001) groups. According to enhancement of inflammatory cytokines in pregnant women with IGT, zinc may be considered as a complimentary supplement together with medical management in patients with IGT and GDM. However, further studies with greater sample size and extended periods of intervention are needed to make definite conclusion.

Plasma zinc levels in Ecuadorian mothers of infants with nonsyndromic cleft lip with or without cleft palate: A case series.

Previous studies have reported an association between maternal zinc deficiency and increased risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring. A high prevalence of zinc deficiency and a high prevalence of NSCL/P have been reported in Ecuador. We postulated that mothers of infants with NSCL/P may have lower serum zinc levels than women from the general population. A case series study was conducted from November 2013 to July 2016. Thirty-five healthy mothers of infants with NSCL/P were selected during surgical missions conducted by Operación Sonrisa Ecuador. A single blood sample along with pertinent medical history was collected during personal interviews after 3.6 months postpartum. The prevalence of plasma zinc concentration (PZn) deficiency among the participants was determined and analyzed along with the prevalence of PZn deficiency in Ecuadorian women of reproductive age from the general population. The mean PZn was 11.47 µmol/dm3 . The prevalence of PZn deficiency among the participants was 31.4% (95% CI: 17.1-48.6) and differed significantly from the prevalence of zinc deficiency observed among women from the general population (G2 = 8.66; p < .05). The results showed that the prevalence of PZn deficiency is lower in a cohort of healthy mothers of infants with NSCL/P than in women from the general population in Ecuador. More studies are required to confirm these findings and evaluate other factors related to NSCL/P pathophysiology in the Ecuadorian population.

Zinc deficiency as a mediator of toxic effects of alcohol abuse.

To review data on the role of ethanol-induced alteration of Zn homeostasis in mediation of adverse effects of alcohol abuse. The scholarly published articles on the association between Zn metabolism and alcohol-associated disorders (liver, brain, lung, gut dysfunction, and fetal alcohol syndrome) have been reviewed. It is demonstrated that alcohol-induced modulation of zinc transporters results in decreased Zn levels in lungs, liver, gut, and brain. Zn deficiency in the gut results in increased gut permeability, ultimately leading to endotoxemia and systemic inflammation. Similarly, Zn deficiency in lung epithelia and alveolar macrophages decreases lung barrier function resulting in respiratory distress syndrome. In turn, increased endotoxemia significantly contributes to proinflammatory state in alcoholic liver disease. Finally, impaired gut and liver functions may play a significant role in alcoholic brain damage, being associated with both increased proinflammatory signaling and accumulation of neurotoxic metabolites. It is also hypothesized that ethanol-induced Zn deficiency may interfere with neurotransmission. Similar changes may take place in the fetus as a result of impaired placental zinc transfer, maternal zinc deficiency, or maternal Zn sequestration, resulting in fetal alcoholic syndrome. Therefore, alcoholic Zn deficiency not only mediates the adverse effects of ethanol exposure, but also provides an additional link between different alcohol-induced disorders. Generally, current findings suggest that assessment of Zn status could be used as a diagnostic marker of metabolic disturbances in alcohol abuse, whereas modulation of Zn metabolism may be a potential tool in the treatment of alcohol-associated disorders.

Maternal dietary zinc supplementation enhances the epigenetic-activated antioxidant ability of chick embryos from maternal normal and high temperatures.

The role of maternal dietary zinc supplementation in protecting the embryos from maternal hyperthermia-induced negative effects via epigenetic mechanisms was examined using an avian model (Gallus gallus). Broiler breeder hens were exposed to two maternal temperatures (21°C and 32°C) × three maternal dietary zinc treatments (zinc-unsupplemented control diet, the control diet + 110 mg zinc/kg inorganic or organic zinc) for 8 weeks. Maternal hyperthermia increased the embryonic mortality and induced oxidative damage evidenced by the elevated mRNA expressions of heat shock protein genes. Maternal dietary zinc deficiency damaged the embryonic development associated with the global DNA hypomethylation and histone 3 lysine 9 hyperacetylation in the embryonic liver. Supplementation of zinc in maternal diets effectively eliminated the embryonic mortality induced by maternal hyperthermia and enhanced antioxidant ability with the increased mRNA and protein expressions of metallothionein IV in the embryonic liver. The increased metallothionein IV mRNA expression was due to the reduced DNA methylation and increased histone 3 lysine 9 acetylation of the metallothionein IV promoter regardless of zinc source. These data demonstrate that maternal dietary zinc addition as an epigenetic modifier could protect the offspring embryonic development against maternal heat stress via enhancing the epigenetic-activated antioxidant ability.

Combined Effects of Gestational Phthalate Exposure and Zinc Deficiency on Steroid Metabolism and Growth.

Disruption of steroid hormone signaling has been implicated independently in the developmental abnormalities resulting from maternal phthalate plasticizer exposure and developmental zinc deficiency. This study investigated if secondary zinc deficiency may result from dietary exposure to a low level of di-2-ethylhexyl phthalate (DEHP) through gestation and if this could be associated with altered steroid metabolism. The interaction between marginal zinc nutrition and DEHP exposure to affect pregnancy outcome, zinc status, and steroid metabolism was also assessed. For this purpose, rats were fed a diet containing an adequate (25 mg/kg) or marginal (10 mg/kg) level of zinc without or with DEHP (300 mg/kg) from gestation day (GD) 0 until GD 19. Steroid profiles were measured in dam liver, plasma, adrenal glands, and in fetal liver by UPLC/MS-MS. In dams fed the adequate zinc diet, DEHP exposure decreased maternal weight gain and led to hepatic acute-phase response and zinc accumulation. The latter could compromise zinc availability to the fetus. DEHP and marginal zinc deficiency caused several adverse effects on the maternal and fetal steroid profiles. Interactions between DEHP exposure and marginal zinc deficient nutrition affected 17OH pregnenolone and corticosterone, while pregnenolone levels were specifically affected by DEHP exposure. Maternal marginal zinc deficiency specifically affected maternal progesterone and aldosterone, and presented evidence of increased androgen aromatization activity in maternal and fetal tissues. Results stress the potential major impact of mild DEHP exposure on maternal/fetal steroid metabolism that can be potentiated by nutritional and chronic disease states leading to zinc deficiency.