Maternal Zn Research Articles

Combined exposure to multiple essential elements and cadmium at early pregnancy on gestational diabetes mellitus: a prospective cohort study.

Minerals and trace elements were involved in the pathogenesis and progression of diabetes. However, the association of mixed exposure to essential elements and toxic elements with gestational diabetes mellitus (GDM) is poorly understood. This study aims to examine the associations between serum calcium (Ca), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and cadmium (Cd) concentrations in early pregnancy and GDM risk in Chinese pregnant women. A total of 1,168 pregnant women were included in this prospective cohort study. The concentrations of serum elements were measured using the polarography method before 14 gestational weeks and an oral glucose tolerance test was conducted at 24-28 gestational weeks to diagnose GDM. Binary logistic regression analysis and restricted cubic spline were applied to evaluate the association between serum individual element and GDM. Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were used to assess the associations between mixed essential elements and Cd exposure and GDM risk. The mean concentrations of Zn (124.65 vs. 120.12 μmol/L), Fe (135.26 vs. 132.21 μmol/L) and Cu (23.33 vs. 23.03 μmol/L) in the GDM group were significantly higher than those in the control group. Single-element modeling results suggested that second and fourth-quartile maternal Zn and Fe concentration, third and fourth-quartile Cu concentration and fourth-quartile Ca concentration were associated with an increased risk of GDM compared to first-quartile values. Restricted cubic spline analysis showed U-shaped and non-linear relationships between Cd and GDM. According to the BKMR models and WQS analyses, a six-element mixture was significantly and positively associated with the risk of GDM. Additionally, Cd, Zn, and Cu contributed the most strongly to the association. Serum Zn, Cu, Fe, and Ca exposure during early pregnancy showed a positive association with GDM in the individual evaluation. The multiple-evaluation showed that high levels of elements mixture, particularly Cd, Zn, and Cu, may promote the development of GDM.

Maternal zinc alleviates tert-butyl hydroperoxide-induced mitochondrial oxidative stress on embryonic development involving the activation of Nrf2/PGC-1α pathway

BackgroundMitochondrial dysfunction induced by excessive mitochondrial reactive oxygen species (ROS) damages embryonic development and leads to growth arrest.ObjectiveThe purpose of this study is to elucidate whether maternal zinc (Zn) exert protective effect on oxidative stress targeting mitochondrial function using an avian model.ResultIn ovo injected tert-butyl hydroperoxide (BHP) increases (P < 0.05) hepatic mitochondrial ROS, malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG), and decreases (P < 0.05) mitochondrial membrane potential (MMP), mitochondrial DNA (mtDNA) copy number and adenosine triphosphate (ATP) content, contributing to mitochondrial dysfunction. In vivo and in vitro studies revealed that Zn addition enhances (P < 0.05) ATP synthesis and metallothionein 4 (MT4) content and expression as well as alleviates (P < 0.05) the BHP-induced mitochondrial ROS generation, oxidative damage and dysfunction, exerting a protective effect on mitochondrial function by enhancing antioxidant capacity and upregulating the mRNA and protein expressions of Nrf2 and PGC-1α.ConclusionsThe present study provides a new way to protect offspring against oxidative damage by maternal Zn supplementation through the process of targeting mitochondria involving the activation of Nrf2/PGC-1α signaling.Graphical

Inferring habitat use of the Pacific White Shark using vertebral chemistry

The conservation and management of highly migratory sharks relies on understanding age-related movements and nursery habitat utilization. We reconstructed the habitat use and migratory history of young White Sharks (Carcharodon carcharias), a highly protected species, by utilizing natural chemical tracers (element:Ca ratios and stable isotope analysis, SIA) in vertebral cartilage growth bands. Two nursery areas in the northeastern Pacific are known, but migration patterns of immature White Sharks within the Gulf of California (GC) and natal philopatry are poorly understood. Vertebrae from coastal Mexican artisanal fisheries off central Baja California in the Pacific (12 neonates and juveniles; 139-280 cm total length) and the GC (3 subadults; 289-355 cm TL) were analyzed to characterize (1) trophic histories from collagen δ13C and δ15N values, and (2) in utero patterns and post-birth environmental histories from element:Ca time-series. Mean δ15N values from vertebral edges of GC sharks, representing the most recent feeding, was +5‰ higher than in the Pacific, reflecting the intense denitrification that permeates the regional food web and supporting SIA as tracers of migration between regions. A subadult from the GC likely resided within the system throughout its life, and two subadults migrated into the GC. Most neonate and juvenile sharks caught in the Pacific had SIA that did not overlap with those of the GC, but a single subadult likely migrated to the GC. Element:Ca ratios displayed ontogenetic trends, with Li:Ca, Zn:Ca, and Ba:Ca significantly higher before the birth mark in sharks captured in the GC. Edge values were significantly higher in Zn:Ca and Ba:Ca in the GC compared to the Pacific, suggesting elemental ratios may serve as tracers of migration between regions. Subadult sharks collected from GC displayed elevated maternal Zn:Ca and Ba:Ca, suggesting mothers may have resided in the GC for an extensive period pre-birth. Some White Sharks may reside within the GC from birth until at least the subadult stage (ca. 3 m TL), and there may be an unidentified nursery. Chemical tracers, coupled with genomic and tagging studies, should improve understanding of the importance of the GC to White Shark populations in the northeast Pacific.

Impact of Maternal and Offspring Dietary Zn Supplementation on Growth Performance and Antioxidant and Immune Function of Offspring Broilers.

The current study investigated the effects of the maternal Zn source in conjunction with their offspring's dietary Zn supplementation on the growth performance, antioxidant status, Zn concentration, and immune function of the offspring. It also explored whether there is an interaction between maternal Zn and their offspring's dietary Zn. One-day-old Lingnan Yellow-feathered broilers (n = 800) were completely randomized (n = 4) between two maternal dietary supplemental Zn sources [maternal Zn-Gly (oZn) vs. maternal ZnSO4 (iZn)] × two offspring dietary supplemental Zn doses [Zn-unsupplemented control diet (CON), the control diet + 80 mg of Zn/kg of diet as ZnSO4]. oZn increased progeny ADG and decreased offspring mortality across all periods, especially during the late periods (p &lt; 0.05). The offspring diet supplemented with Zn significantly improved ADG and decreased offspring mortality over the whole period compared with the CON group (p &lt; 0.05). There were significant interactions between the maternal Zn source and offspring dietary Zn with regards to progeny mortality during the late phase and across all phases as a whole (p &lt; 0.05). Compared with the iZn group, the oZn treatment significantly increased progeny liver and serum Zn concentrations; antioxidant capacity in the liver, muscle, and serum; and the IgM concentration in serum; while also decreasing progeny serum IL-1 and TNF-α cytokine secretions (p &lt; 0.05). Similar results were observed when the offspring diet was supplemented with Zn compared with the CON group; moreover, adding Zn to the offspring diet alleviated progeny stress by decreasing corticosterone levels in the serum when compared to the CON group (p &lt; 0.05). In conclusion, maternal Zn-Gly supplementation increased progeny performance and decreased progeny mortality and stress by increasing progeny Zn concentration, antioxidant capacity, and immune function compared with the same Zn levels from ZnSO4. Simultaneously, Zn supplementation in the progeny's diet is necessary for the growth of broilers.

Determination of Time Progression and Sensitive Biomarkers of Maternal Zinc Depletion in Broiler Chickens and Pekin Ducks Fed a Zinc-Deficient Diet.

Two experiments were performed to assess maternal zinc (Zn) depletion in broiler chickens and Pekin ducks fed a Zn-deficient diet. The time of Zn depletion was assessed based on growth performance, and sensitive biomarkers were determined based on tissue Zn content via a linear regression model. A total of 200 1-day-old male broiler chickens (experiment 1) and 200 1-day-old male Pekin ducks (experiment 2) were randomly allocated to 2 diets with 10 replicate cages (10 birds/cage). The two diets were a zinc-deficient diet (ZnD, 20.42mg Zn/kg) and a control zinc diet (CON, 84.77mg Zn/kg). In experiment 1, compared to CON, ZnD decreased (P < 0.05) the body weight (days 7, 14, and 21), body weight gain, feed intake (days 1-7, 1-14, and 1-21), and the Zn content of plasma (days 7 and 21), pancreas (days 7, 14, and 21), and tibia in broiler chickens. The R2 of a linear model was greater at day 7 than at day 14 or day 21 for pancreatic Zn content in broiler chickens. In experiment 2, compared to CON, ZnD also decreased (P < 0.05) the body weight (days 7, 14, and 21), body weight gain (days 1-7, 1-14, and 1-21), and feed intake (days 1-14 and 1-21) and increased (P < 0.05) the feed-to-gain ratio (days 1-7 and 1-14) in ducks. Compared with CON, ZnD reduced (P < 0.05) the Zn content of the pancreas (days 7, 14, and 21), tibia (days 7, 14, and 21), and skin (days 14 and 21) and increased (P < 0.05) the Zn content of the plasma (day 21) and skin (day 7) in ducks. The R2 of a linear model was greater at day 7 than at days 14 or 21 for skin Zn content in ducks. The results indicated that the maternal Zn was depleted by 7days of age in both birds; the sensitive biomarker for broiler chickens is pancreatic Zn content, and for ducks, it is skin Zn content.

Maternal serum zinc level is associated with risk of preeclampsia: A systematic review and meta-analysis.

BackgroundPreeclampsia (PE) is a multi-organ syndrome that onsets in the second half of pregnancy. It is the second leading cause of maternal death globally. The homeostasis of zinc (Zn) levels is important for feto-maternal health.ObjectiveWe aimed to collect all studies available to synthesize the evidence regarding the association between maternal Zn levels and the risk of preeclampsia.MethodsA systematic review and meta-analysis was conducted via searching seven electronic databases [PubMed, Web of Science, Embase, African Journals Online (AJOL), ClinicalTrial.gov, and two Chinese databases: Wanfang and Chinese National Knowledge Infrastructure, CNKI]. Studies reporting maternal serum Zn levels in pregnant women with or without preeclampsia were included. Eligible studies were assessed through Newcastle-Ottawa Scale (NOS) and the meta-analysis was performed via RevMan and Stata. The random-effects method (REM) was used for the meta-analysis with 95% confidence interval (CI). The pooled result was assessed using standard mean difference (SMD). The heterogeneity test was carried out using I2 statistics, and the publication bias was evaluated using Begg's and Egger's test. Meta-regression and sensitivity analysis was performed via Stata software.ResultsA total of 51 studies were included in the final analysis. 6,947 participants from 23 countries were involved in our study. All studies went through the quality assessment. The pooled results showed that maternal serum Zn levels were lower in preeclamptic women than in healthy pregnant women (SMD: −1.00, 95% CI: −1.29, −0.70). Sub-group analysis revealed that geographical, economic context, and disease severity may further influence serum Zn levels and preeclampsia.LimitationsThere are significant between-study heterogeneity and publication bias among included studies.ConclusionsA lower level of maternal Zn was associated with increased risks of preeclampsia. The associations were not entirely consistent across countries and regions worldwide.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=337069, Identifier: CRD42022337069

The effect of zinc on human trophoblast proliferation and oxidative stress

Adequate Zinc (Zn) intake is required to prevent multiple teratogenic effects however deviations from adequate Zn intake, including high maternal Zn status, have been linked to increased incidence of pregnancy complications, including those associated with inadequate placentation. Using placental trophoblast HTR8/SVneo cells and first trimester human placental explants (n = 12), we assessed the effects of varying Zn concentrations on trophoblast proliferation, viability, apoptosis and oxidative stress. Compared to physiologically normal Zn levels (20 µM), HTR-8/SVneo cell proliferation index was significantly lower in the presence of physiologically elevated (40 µM; P = .020) and supra-physiological (80 µM; P = .007) Zn. The latter was also associated with reduced proliferation (P = .004) and viability (P < .0001) in cultured placental explants, but not apoptosis. Reactive oxygen species production in HTR8/SVneo cultures was significantly higher in the presence of 80 µM Zn compared to all physiologically relevant levels. Oxidative stress, induced by an oxidizing agent menadione, was further exacerbated by high (80 µM) Zn. Zn did not affect lipid peroxidation in either HTR8/SVneo cells or placental explants or antioxidant defense mechanisms that included glutathione reductase and superoxide dismutase. Further study should focus on elucidating mechanisms behind impaired trophoblast proliferation and increased oxidative stress as a result of elevated Zn levels.

Zinc supplementation within the reference ranges for zinc status in cattle improves sperm quality without modifying in vitro fertilization performance

Zinc (Zn) has important functions in mammalian reproductive processes. In cattle, Zn status can be classified as deficient, marginal, and adequate, depending on the plasma Zn concentration. In addition, Zn deficiency can lead to reproductive failure. The aim of this study was to investigate the effect of maternal Zn status at the beginning of a fixed-time artificial insemination (FTAI) treatment regimen on pregnancy rate in cattle, and evaluate the effect of supplementing in vitro fertilization (IVF) medium with Zn concentrations within the reference range for Zn status on sperm quality and IVF performance. Pregnancy rates of animals with marginal and adequate Zn status did not differ, and there were no Zn-deficient animals detected. Supplementation of 0.8 μg/mL Zn to IVF medium enhanced progressive motility, sperm viability, functional sperm membrane integrity (HOST), acrosomal integrity and sperm-zona binding, without modifying pronuclear formation, or development of embryos to the cleavage or blastocyst stage after IVF. In conclusion, the present results indicate pregnancy rates are not associated with maternal Zn status at the beginning of the FTAI treatment regimen if Zn status is marginal or adequate. Furthermore, supplementation of IVF medium with Zn at concentrations which is considered adequate for Zn status in cattle led to improved sperm quality, without having effects on embryo development in cattle.

Association of maternal serum trace elements with newborn screening-thyroid stimulating hormone

Abstract Objectives Trace elements are essential in thyroid functioning as they incorporate into biologically important enzymes as cofactors. The placenta can either activate or inhibit the transfer of maternal trace elements to the unborn. An imbalance of maternal trace elements in pregnancy may affect both maternal and newborn thyroid function. Methods Blood samples from 315 lactating mothers were collected in the first 48 h after delivery and evaluated for selenium (Se), copper (Cu), manganese (Mn), and zinc (Zn) using flame atomic absorption spectroscopy (FAAS) and quadrupole inductively coupled plasma-mass spectrometer (ICP-MS). Thyroid hormones and auto-antibodies (thyroid-stimulating hormone (TSH), free T3 (fT3), free T3 (fT4), anti–thyroid peroxidase (anti-TPO), and antithyroglobulin (anti-TG)) were analyzed in maternal blood using an electro-chemiluminescence immunoassay (ECLIA). Between 48 and 72 postpartum hours, spot blood samples were used for newborn screening-TSH measurement. Correlation and multivariate analyses were performed to evaluate the effect of maternal trace element levels on newborn screening-TSH levels. Results The medians (min-max) of maternal Se (45.16 µg/L (21.28–79.04)), Cu (210.10 µg/dL (117.04–390.64)), Mn (2.11 µg/L (0.20–3.46)), and Zn (0.43 mg/L (0.24–0.66)) were determined. A positive correlation was detected between Zn and maternal TSH levels (r=0.12, p &lt; 0.05). Newborn screening-TSH was significantly correlated with maternal Cu (r=0.14, p &lt; 0.01). Similarly, Cu exhibited weak associations in clustering analysis while others shared common clusters with newborn-screening TSH. Conclusions There was no significant association between most of the maternal serum trace elements and maternal thyroid hormone parameters, with an only exception between maternal Zn and maternal serum TSH. Finally, the association between maternal serum Cu levels and newborn screening-TSH levels may highlight the importance of maternal Cu levels on the newborn thyroid health.

The effect of zinc supplementation in delayed preterm delivery and biometric of neonates suspected with preterm delivery in mothers suspected of having a preterm delivery

Background and aims: Micronutrient deficiency in women of reproductive age is considered as a major health problem in many developing countries. Therefore, it is important to prevent micronutrient shortage before pregnancy. This study aimed to evaluate the effect of zinc (Zn) supplementation on delaying preterm delivery and biometric neonates with suspected preterm birth. Methods: In this semi-experimental study, 140 women with preterm delivery were selected by a gynecologist in the Hajar hospital of Shahrekord University of Medical Sciences in 2016. The women were divided into four groups. Then, the serum Zn level of the mother’s blood and the umbilical cord was measured First group had a normal level; Zn level in the second group was between 50-70 mg/dL; in the third group between 20-50 mg/dL; and in the fourth group fewer than 20 mg/dL. Three groups received &lt;20-70 mg/dL oral Zn and the normal group was given a placebo. Next, the serum Zn levels of mothers were measured and recorded at the end of the eighth month and delivery time. Infant anthropometric parameters at birth, 1 month to 3 months were measured as well. Overall, 71 (50%) and 69 (49.3%) infants were males and females, respectively. The data were analyzed using descriptive statistics and analytical statistics tests. Results: The average age of 140 pregnant women was 30.39±5.33 years old and their age range was between 18 and 41 years. In addition, the maternal Zn serum level was 56.52±33.38 mg/dL on admission and the serum level on the cord blood at birth was 53.22 ± 66.94 μg/ dL. A significant relationship was reported between the level of serum Zn on cord blood and the maternal serum Zn level on admission with growth in babies at birth and the first, second, and third month (P&lt;0.05). Conclusion: In general, Zn is effective in children’s growth and the use of Zn supplementation can be suggested during pregnancy.

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.

Effects of Maternal Zinc Glycine on Mortality, Zinc Concentration, and Antioxidant Status in a Developing Embryo and 1-Day-Old Chick.

This study was conducted to investigate the effects of maternal zinc glycine (Zn-Gly) supplementation as an alternative for zinc sulfate (ZnSO4) on mortality, zinc (Zn) concentration, and antioxidant status in a developing embryo and 1-day-old chick. Six hundred 39-week-old broiler breeders were randomly assigned to 6 treatments, each treatment including 5 replicates with 20 birds each. Six treatments received a basal diet (control, 24mg Zn/kg diet) or a basal diet supplemented with ZnSO4 (80mg Zn/kg) or Zn-Gly (20, 40, 60, or 80mg Zn/kg), respectively. The experiment lasted for 8weeks after a 4-week pre-experiment with a basal diet. At the last week, 100 eggs per replicate were randomly collected for incubation. Compared with the control treatment, Zn supplementation decreased (P<0.05) embryo mortalities of the late stage and the whole period, increased (P<0.05) liver Zn concentration in the embryo of d9, d19, and 1-day-old chick, and improved (P<0.05) antioxidant status in the embryo of d19 and 1-day-old chick. Compared with the ZnSO4 treatment, 80mg Zn/kg Zn-Gly treatment significantly decreased (P<0.05) the late stage embryo mortality and increased (P<0.05) liver Zn concentration in the embryo of d9, d19, and 1-day-old chick. The 80mg Zn/kg Zn-Gly treatment significantly increased (P<0.05) copper-zinc superoxide dismutase activity in d19 embryo and 1-day-old chick, total superoxide dismutase activity in 1-day-old chick, and copper-zinc superoxide dismutase messenger RNA (mRNA) abundance of d9 embryo and 1-day-old chick than that in ZnSO4 treatment. The liver metallothionein concentration of the developing embryo and 1-day-old chick and its mRNA abundance of d19 embryo were also significantly increased (P<0.05) in the 80mg Zn/kg Zn-Gly treatment in comparison with ZnSO4 treatment. In conclusion, maternal Zn supplementation decreased embryo mortalities of the late stage and the whole period by increasing liver Zn concentration and antioxidant status in d19 embryo and 1-day-old chick, and 80mg Zn/kg from Zn-Gly treatment was the optimum choice.

Involvement of Zn Depletion in Cd-Induced Toxicity on Prenatal Bone Formation in Rat.

This study explored the potential toxicity of Cd on the Zn bone depletion in prenatal bone formation. Female rats received either tap water, Cd, Zn, or Cd + Zn in their drinking water during gestation, and some markers of bone formation were studied in their fetuses removed at the 20th day of pregnancy (GD20). Cd exposure induced maternal hypozincemia and Zn depletion in the femur of the fetuses. A striking inhibition of bone formation in fetuses, expressed by decreases in femur length, width, and area, by the shortening of diaphysis, and by a decrease in length and area of distal and proximal proliferative zones, was observed in fetuses from Cd-exposed mothers. At the molecular level, Cd caused upregulation of MT-1 and ZIP2 genes and significantly depressed the expression of the ZnT5, colα1, osteocalcin, and ALP genes in the femur. Interestingly, Zn treatment ameliorated the Cd-induced maternal hypozincemia and femoral changes and partially restored the normal histomorphometry of the femur. These results suggest that the observed toxic effects of Cd are, at least in part, mediated by the disruption of maternal Zn metabolism during pregnancy leading to Zn depletion and thus to perturbation of prenatal bone formation.

Associations of Maternal Serum Zonulin and Elements Concentrations with Neonatal Birth Weight: A Case-Control Study

Introduction: Intake of micronutrients and zonulin levels (as a marker for intestinal permeability) during pregnancy can be effective on birth weight of infants. However, no studies have investigated the relationship between the infants birth weight and maternal zonulin level. Aim: This study aimed to compare the zonulin levels and maternal trace elements in infants with low birth weight (LBW) and Normal Birth Weight (NBW) and its relationship with weight, length and head circumference of infants. Materials and Methods: In this study, 368 infants were divided into two groups: case (n=82) with birth weight of = 2500 gm. Maternal zonulin, zinc, calcium, copper and iron levels were evaluated. Weight, length and head circumference of infants were measured. The maternal serum level zonulin and micronutrients between the two groups were assessed using Student t-test or Chi-squared test and the relationship between variables using Spearman's rank correlation. Results: A significant difference was seen in the maternal zonulin and zinc serum levels between the LBW and the NBW infants (<0.001). No significant difference was observed in the calcium, copper, and iron levels between the two groups. A significant positive relationship was seen between maternal serum zonulin and zinc concentration with the birth weight of the LBW infants (respectively r=0.45 and r=0.41) (p<0.05). No relationship was seen between maternal serum zonulin and zinc concentration with the length and head circumference of the infants. Conclusion: The results showed that the maternal serum Zn level is associated with the infants birth weight. In addition, intestinal permeability, as a new factor could affect the birth weight and birth rate of the LBW infants. Further studies in this area are recommended.

Redistribution of tissue zinc pools during lactation and dyshomeostasis during marginal zinc deficiency in mice

Zinc (Zn) requirements are increased during lactation. Increased demand is partially met through increased Zn absorption from the diet. It is estimated that 60–80% of women of reproductive age are at risk for Zn deficiency due to low intake of bioavailable Zn and increased demands during pregnancy and lactation. How Zn is redistributed within the body to meet the demands of lactation, and how Zn deficiency affects this process, is not understood. Female C57bl/6J mice were fed a control (ZA; 30mg Zn/kg) or a marginally Zn deficient (ZD; 15mg Zn/kg) diet for 30 days prior to mating through mid-lactation and compared with nulliparous mice fed the same diets. While stomach and plasma Zn concentration increased during lactation in mice fed ZA, mice fed ZD had lower stomach Zn concentration and abrogated plasma Zn levels during lactation. Additionally, femur Zn decreased during lactation in mice fed ZA, while mice fed ZD did not experience this decrease. Furthermore, red blood cell, pancreas, muscle and mammary gland Zn concentration increased, and liver and adrenal gland Zn decreased during lactation, independent of diet, while kidney Zn concentration increased only in mice fed ZD. Finally, maternal Zn deficiency significantly increased the liver Zn concentration in offspring but decreased weight gain and survival. This study provides novel insight into how Zn is redistributed to meet the increased metabolic demands of lactation and how marginal Zn deficiency interferes with these homeostatic adjustments.

Effect of zinc (Zn) deficiency on nutrient delivery to the rat fetus

Maternal Zn deficiency can result in fetal growth retardation and reductions in fetal insulin‐like growth factor‐1 (IGF‐1). Fetal growth is driven by IGF‐1 but is also influenced by the maternal nutrient supply. Accordingly, one aim of the current study was to examine the delivery of nutrients across the placenta under conditions of Zn adequacy and deficiency. Beginning at conception rat dams consumed a Zn adequate (25 ppm Zn) or Zn deficient (0.3 ppm Zn) diet, while a third group of rats were restricted in the amount of adequate diet they received to a level equivalent to the diet consumed by the Zn deficient dams. Dams were anesthetized at GD 19.5 with isoflurane and injected with 10 μCi/kg of [14C] methyl‐aminoisobutyric acid, an amino acid analog. After 7 min, dams were euthanized and maternal serum, fetuses, and placentas were collected. Fetuses were homogenized in PBS. Aliquots of homogenate and maternal serum were precipitated with trifluoroacetic acid, and the supernates were measured for DPMs. Maternal DPM per ml serum and DPM per g fetus was similar among the groups. These data suggest that amino acid delivery was unaffected by Zn deficiency. Our previous finding indicated that fetal liver IGF‐ 1 levels are attenuated during maternal Zn deficiency. When coupled with the current findings, the data suggest that the fetal regulation of its own growth is directly compromised under conditions of Zn deficiency. This work was supported by Center for Health and Nutrition Research.

Marginal Maternal Zinc Deficiency in Lactating Mice Reduces Secretory Capacity and Alters Milk Composition ,

Dietary analysis predicts that marginal Zn deficiency is common in women of reproductive age. The lack of reliable biomarkers limits the capacity to assess Zn status and consequently understand effects of maternal Zn deficiency. We determined effects of marginal maternal Zn deficiency on mammary gland function, milk secretion, and milk composition in mice. Mice (n = 12/diet) were fed marginal (ZD; 15 mg Zn/kg diet) or adequate (ZA; 30 mg Zn/kg diet) Zn diets for 30 d prior to conception through mid-lactation. Mice fed the ZD had a higher plasma Zn concentration (~20%; P < 0.05) but lower milk Zn concentration (~15%; P < 0.05) compared with mice fed the ZA. ZnT2 abundance was higher (P < 0.05) in mice fed the ZD compared with mice fed the ZA; no effect on ZnT4 abundance was detected. The Zn concentration of mammary gland mitochondria tended to be ~40% greater in mice fed ZD (P = 0.07); this was associated with apoptosis and lower milk secretion (~80%; P < 0.01). Total milk protein was ~25% higher (P < 0.05), although the abundance of the major milk proteins (caseins and whey acidic protein) was lower (P < 0.05) in mice fed the ZD. Proteomic analysis of milk proteins revealed an increase (P < 0.05) in four proteins in mice fed the ZD. These findings illustrate that marginal maternal Zn deficiency compromises mammary gland function and milk secretion and alters milk composition. This suggests that lactating women who consume inadequate Zn may not produce and/or secrete an adequate amount of high quality milk to provide optimal nutrition to their developing infant.

Maternal zinc restriction affects postnatal growth and glucose homeostasis in rat offspring differently depending upon adequacy of their nutrient intake

We have previously investigated effects of moderate maternal zinc (Zn) restriction on growth and glucose homeostasis in offspring, but interaction between maternal Zn restriction and postnatal nutrition have not been studied. Weight and serum Zn were lower in ZnD-IN than in ZnC-IN rats at wk 3, but ZnD-AN and ZnD-EN rats had greater weights than respective controls and higher insulin-like growth factor-1 (ZnD-AN) and leptin levels (ZnD-EN). Subsequently, both ZnD-AN and ZnD-EN pups were insulin resistant, and had evidence of elevated serum leptin and depressed insulin receptor phosphorylation with gender-specific differences up to 15 weeks. Maternal Zn restriction interacted with postnatal nutritional status, resulting in divergent effects on weight gain and insulin resistance. Interaction between potential effects of fetal Zn restriction and food availability postnatally may be one factor responsible for later metabolic derangements. Rats were fed Zn restricted (ZnD, 7 μg/g) or control (ZnC, 25 μg/g) diets ad libitum from 3 wk pre-conception to 3 wk post-parturition. Postnatally, litters were culled to 13 (IN, inadequate nutrition), 7 (AN, adequate nutrition), and 4 (EN, excess nutrition) pups/dam, respectively, and nursed by their original mothers. Postweaning, pups were fed rodent diet ad libitum. Tests to assess insulin resistance were performed subsequently.

Relationships of maternal zinc intake from animal foods with fetal growth

Zn is an essential element for human growth. The nutritional adequacy of dietary Zn depends not only on the total Zn intake, but also on the type of food source (i.e. of plant or animal origin). We investigated the association between maternal dietary Zn intake from animal and plant food sources and fetal growth. A total of 918 pregnant women at 12-28 weeks of gestation were selected from the Mothers and Children's Environmental Health study in Korea. Dietary intakes in mid-pregnancy were estimated by a 24 h recall method, and subsequent birth weight and height were obtained from medical records. Multiple regression analysis showed that maternal Zn intake from animal food sources and their proportions relative to total Zn intake were positively associated with birth weight (P = 0.034 and 0.045, respectively) and height (P = 0.020 and 0.032, respectively). Conversely, the percentage of Zn intake from plant food sources relative to total Zn intake was negatively associated with birth height (P = 0.026) after adjustment for covariates that may affect fetal growth. The molar ratio of phytate:Zn was negatively associated with birth weight (P = 0.037). In conclusion, we found that the absolute amounts of Zn from different food sources (e.g. animal or plant) and their proportions relative to total Zn intake were significantly associated with birth weight and height. A sufficient amount of Zn intake from animal food sources of a relatively higher Zn bioavailability is thus encouraged for women during pregnancy.

Maternal Zinc Deficiency in Rats Affects Growth and Glucose Metabolism in the Offspring by Inducing Insulin Resistance Postnatally ,

Interactions among zinc (Zn), insulin, and glucose metabolism are complex. Maternal Zn deficiency affects maternal carbohydrate metabolism, but the mechanisms underlying changes in glucose homeostasis of offspring are not well understood. Rats consumed Zn-deficient (ZnD; 7 mug/g) or control (ZnC; 25 mug/g) diets ad libitum from 3 wk preconception to 21 d postparturition. Litters were culled to 7 pups/dam postnatally and pups were allowed to nurse their original mothers; after weaning, pups were fed nonpurified diet. Insulin and glucose tolerance tests were performed on the pups at wk 5 and 10. Although there was no difference in birth weight between groups, ZnD pups weighed significantly more than controls by d 10 (+5%) and 20 (+10%). Both blood glucose and serum insulin-like growth factor (IGF-1) concentrations at wk 3 were significantly higher in ZnD pups than in controls. Both male and female ZnD rats were less sensitive to insulin and glucose stimulation than controls at wk 5 and 10. At wk 15, serum leptin concentrations were higher in male ZnD rats than in controls. Phosphorylation of muscle Akt protein, an insulin receptor (IR) signaling intermediate, was lower in female ZnD rats than in controls at wk 15, but they did not differ in phosphorylation of IR. Maternal Zn deficiency resulted in greater serum IGF-1 concentrations and the excessive postnatal weight gain in their offspring as well as impaired subsequent glucose sensitivity. It was associated with gender-specific alterations in the serum leptin concentration and the insulin signaling pathway. These findings suggest that suboptimal maternal Zn status induces long-term changes in the offspring related to abnormal glucose tolerance.