The effect of zinc on human trophoblast proliferation and oxidative stress |
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| Affiliation: | 1. Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, Australia;2. Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia;3. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia;4. School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Adelaide, SA, Australia;5. CSIRO Health and Biosecurity, Future Science Platforms Probing Biosystems, Adelaide, SA, Australia;6. School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia;1. Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Centre of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil;2. Multicentre Graduate Program in Physiological Sciences, Centre of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil;3. Graduate Program in Nutrition, Centre of Health Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil;4. Department of Physiology and Pathology, School of Dentistry, São Paulo State University - UNESP, Araraquara, São Paulo, Brazil;1. Federal Research Centre of Nutrition and Biotechnology, Moscow, Russia;2. Plekhanov Russian University of Economics, Moscow, Russia;1. Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan;2. Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan,;3. Department of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan,;4. Research Center for Development Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan;1. Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata, Japan;2. Department of Immunology, Faculty of Medicine, Yamagata University, Yamagata, Japan;3. Department of Pathological Diagnostics, Faculty of Medicine, Yamagata University, Yamagata, Japan;4. Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan;5. AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, Japan;6. Miyata Diabetes and Metabolism Clinic, Fukushima-ku, Osaka, Japan |
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| Abstract: | 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. |
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