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.

OBJECTIVES: Zinc, which is found in high concentrations in the ß-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. METHODS: The 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 ß-cells by immunohistochemistry. RESULTS: The 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. CONCLUSION: The 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.

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

BACKGROUND: Mitochondrial dysfunction induced by excessive mitochondrial reactive oxygen species (ROS) damages embryonic development and leads to growth arrest. OBJECTIVE: The purpose of this study is to elucidate whether maternal zinc (Zn) exert protective effect on oxidative stress targeting mitochondrial function using an avian model. RESULT: In 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. CONCLUSIONS: The 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.

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, 20.42 mg Zn/kg) and a control zinc diet (CON, 84.77 mg 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 7 days of age in both birds; the sensitive biomarker for broiler chickens is pancreatic Zn content, and for ducks, it is skin Zn content.

Prenatal Zinc Supplementation Ameliorates Hippocampal Astrocytes Activation and Inflammatory Cytokines Expression Induced by Lipopolysaccharide in a Rat Model of Maternal Immune Activation.

Introduction: Evidence suggests that gestational exposure to Lipopolysaccharide (LPS) results in fetal zinc deficiency and eventually neurodevelopmental abnormalities. In this study, we utilized a rat model of Maternal Immune Activation (MIA) to investigate the possible neuroprotective effects of zinc supplementation during pregnancy on hippocampal astrocytes activation as well as inflammatory cytokines expression in adult offspring. Methods: Pregnant rats received intraperitoneal injections of either LPS (0.5 mg/kg) or saline on Gestational Days (GD) 15 and 16, and orally gavaged with zinc sulfate (30 mg/kg) during pregnancy. Astrocyte density and histological assessment were evaluated in the hippocampus of adult offspring on Postnatal Days (PND) 60 to 62. Also, the mRNA levels of IL-6, TNF-α, IL-1ß, NF-κB, and GFAP were measured using qPCR analysis. Results: Prenatal exposure to LPS resulted in upregulated expression levels of IL-6, TNF-α, NF-κB, and GFAP in the hippocampus of adult pups. Moreover, the offspring from the LPS group showed an increased astrocyte density in the CA1 region with no histological alterations in CA1 and CA3 areas. However, maternal zinc supplementation ameliorated the LPS-induced inflammatory alterations. Conclusion: This study supports the premise that zinc supplementation during pregnancy might be an early treatment option to inhibit hippocampal inflammation induced by the maternal immune response to infectious agents. Highlights: Maternal immune activation induced mild hippocampal inflammation in adult offspring.Zinc supplementation suppressed LPS-induced hippocampal inflammation in offspring.Zinc might be an early therapeutic option to inhibit neurodevelopmental impairments. Plain Language Summary: Schizophrenia is a chronic and disabling psychiatric disorder, affecting an estimated one percent of the world's population. To date, the biological mechanisms underlying this mental disorder remain largely elusive, however, research has demonstrated the involvement of both genetic and environmental factors. Of environmental factors, gestational exposure to rubella, influenza, and genital-reproductive infections have gained particular interest among researchers. Based on this evidence, in the present study, we used an animal model of schizophrenia and showed the beneficial effect of zinc supplementation during pregnancy to protect against LPS-induced inflammation in the hippocampus of adult offspring. Collectively, our study provides support for the premise that early treatment might be a suitable option to prevent schizophrenia risk in progeny.

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 < 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 < 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 < 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 < 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 < 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.

Mechanisms Underlying the Protective Effect of Maternal Zinc (ZnSO4 or Zn-Gly) against Heat Stress-Induced Oxidative Stress in Chicken Embryo.

Environmental factors such as high temperature can cause oxidative stress and negatively affect the physiological status and meat quality of broiler chickens. The study was conducted to evaluate the effects of dietary maternal Zn-Gly or ZnSO4 supplementation on embryo mortality, hepatocellular mitochondrial morphology, liver antioxidant capacity and the expression of related genes involved in liver oxidative mechanisms in heat-stressed broilers. A total of 300 36-week-old Lingnan Yellow broiler breeders were randomly divided into three treatments: (1) control (basal diet, 24 mg zinc/kg); (2) inorganic ZnSO4 group (basal diet +80 mg ZnSO4/kg); (3) organic Zn-Gly group (basal diet +80 mg Zn-Gly/kg). The results show that maternal zinc alleviated heat stress-induced chicken embryo hepatocytes' oxidative stress by decreasing the content of ROS, MDA, PC, 8-OHdG, and levels of HSP70, while enhancing T-SOD, T-AOC, CuZn-SOD, GSH-Px, CTA activities and the content of MT. Maternal zinc alleviated oxidative stress-induced mitochondrial damage in chick embryo hepatocytes by increasing mitochondrial membrane potential and UCP gene expression; and Caspase-3-mediated apoptosis was alleviated by increasing CuZn-SOD and MT gene expression and decreasing Bax gene expression and reducing the activity of caspase 3. Furthermore, maternal zinc treatment significantly increased Nrf2 gene expression. The results above suggest that maternal zinc can activate the Nrf2 signaling pathway in developing chick embryos, enhance its antioxidant function and reduce the apoptosis-effecting enzyme caspase-3 activities, thereby slowing oxidative stress injury and tissue cell apoptosis.

Effect of maternal zinc deficiency on offspring health: The epigenetic impact.

BACKGROUND: Zinc deficiency is associated with adverse effects on maternal health and pregnancy outcomes. These consequences have been reported over the years from zinc supplementation trials and observational studies whereby outcomes of maternal, foetal and infant health were measured. Owing to the importance of zinc in the functions of epigenetic enzymes, pre-clinical studies have shown that its deficiency could disrupt biological activities that involve epigenetic mechanisms in offspring. Thus, this review assessed the link between epigenetics and the effects of maternal zinc deficiency on the offspring's health in animal studies. METHODS: Research articles were retrieved without date restriction from PubMed, Web of Science, ScienceDirect, and Google Scholar databases, as well as reference lists of relevant articles. The search terms used were "zinc deficiency", "maternal zinc deficiency", "epigenetics", and "offspring." Six studies met the eligibility criteria and were reviewed. RESULTS: All the eligible studies reported maternal zinc deficiency and observed changes in epigenetic markers on the progeny during prenatal and postnatal stages of development. The main epigenetic markers reported were global and gene specific methylation and/ or acetylation. The epigenetic changes led to mortality, disruption in development, and risk of later life diseases. CONCLUSION: Maternal zinc deficiency is associated with epigenetic modifications in offspring, which induce pathologies and increase the risk of later life diseases. More research and insight into the epigenetic mechanisms could spring up new approaches to combat the associated disease conditions.

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, 24 mg Zn/kg diet) or a basal diet supplemented with ZnSO4 (80 mg Zn/kg) or Zn-Gly (20, 40, 60, or 80 mg Zn/kg), respectively. The experiment lasted for 8 weeks 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, 80 mg 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 80 mg 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 80 mg 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 80 mg Zn/kg from Zn-Gly treatment was the optimum choice.