title: Adverse effects of parental zinc deficiency on metal homeostasis and embryonic development in a zebrafish model.
abstract: The high prevalence of zinc deficiency is a global public health concern, and suboptimal maternal zinc consumption has been associated with adverse effects ranging from impaired glucose tolerance to low birthweights. The mechanisms that contribute to altered development and poor health in zinc deficient offspring are not completely understood. To address this gap, we utilized the Danio rerio model and investigated the impact of dietary zinc deficiency on adults and their developing progeny. Zinc deficient adult fish were significantly smaller in size, and had decreases in learning and fitness. We hypothesized that parental zinc deficiency would have an impact on their offspring's mineral homeostasis and embryonic development. Results from mineral analysis showed that parental zinc deficiency caused their progeny to be zinc deficient. Furthermore, parental dietary zinc deficiency had adverse consequences for their offspring including a significant increase in mortality and decreased physical activity. Zinc deficient embryos had altered expression of genes that regulate metal homeostasis including several zinc transporters (ZnT8, ZnT9) and the metal-regulatory transcription factor 1 (MTF-1). Zinc deficiency was also associated with decreased expression of genes related to diabetes and pancreatic development in the embryo (Insa, Pax4, Pdx1). Decreased expression of DNA methyltransferases (Dnmt4, Dnmt6) was also found in zinc deficient offspring, which suggests that zinc deficiency in parents may cause altered epigenetic profiles for their progeny. These data should inform future studies regarding zinc deficiency and pregnancy and suggest that supplementation of zinc deficient mothers prior to pregnancy may be beneficial.
authors.affiliation: Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331, United States; Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331, United States. Electronic address: Laura.Beaver@oregonstate.edu.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Beaver
authors.affiliation: Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331, United States; Department of Environmental and Molecular Toxicology, Oregon State University, Sinnhuber Aquatic Research Laboratory, 1007 Agriculture & Life Sciences Building, Corvallis, OR 97331, United States; The Environmental Health Sciences Center, Oregon State University, 1011 Agriculture & Life Sciences Building, Corvallis, Oregon 97331, United States. Electronic address: yasmeen.nkrumah-elie@ucdenver.edu.
authors.forename: Yasmeen M
authors.initials: YM
authors.lastname: Nkrumah-Elie
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Sinnhuber Aquatic Research Laboratory, 1007 Agriculture & Life Sciences Building, Corvallis, OR 97331, United States; The Environmental Health Sciences Center, Oregon State University, 1011 Agriculture & Life Sciences Building, Corvallis, Oregon 97331, United States. Electronic address: Lisa.Truong@oregonstate.edu.
authors.forename: Lisa
authors.initials: L
authors.lastname: Truong
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Sinnhuber Aquatic Research Laboratory, 1007 Agriculture & Life Sciences Building, Corvallis, OR 97331, United States; The Environmental Health Sciences Center, Oregon State University, 1011 Agriculture & Life Sciences Building, Corvallis, Oregon 97331, United States. Electronic address: Carrie.Barton@oregonstate.edu.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Barton
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Sinnhuber Aquatic Research Laboratory, 1007 Agriculture & Life Sciences Building, Corvallis, OR 97331, United States; The Environmental Health Sciences Center, Oregon State University, 1011 Agriculture & Life Sciences Building, Corvallis, Oregon 97331, United States. Electronic address: andrea.knecht@tanguaylab.com.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Knecht
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Sinnhuber Aquatic Research Laboratory, 1007 Agriculture & Life Sciences Building, Corvallis, OR 97331, United States; The Environmental Health Sciences Center, Oregon State University, 1011 Agriculture & Life Sciences Building, Corvallis, Oregon 97331, United States. Electronic address: gman@oregonstate.edu.
authors.forename: Greg D
authors.initials: GD
authors.lastname: Gonnerman
authors.affiliation: Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331, United States; Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331, United States. Electronic address: Carmen.Wong@oregonstate.edu.
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Wong
authors.affiliation: Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331, United States; Department of Environmental and Molecular Toxicology, Oregon State University, Sinnhuber Aquatic Research Laboratory, 1007 Agriculture & Life Sciences Building, Corvallis, OR 97331, United States; The Environmental Health Sciences Center, Oregon State University, 1011 Agriculture & Life Sciences Building, Corvallis, Oregon 97331, United States; Center for Genome Research and Biocomputing, Oregon State University, 3021 Agriculture and Life Sciences Building, Corvallis, OR 97331, United States. Electronic address: Robert.Tanguay@oregonstate.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Tanguay
authors.affiliation: Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331, United States; Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331, United States; The Environmental Health Sciences Center, Oregon State University, 1011 Agriculture & Life Sciences Building, Corvallis, Oregon 97331, United States; Center for Genome Research and Biocomputing, Oregon State University, 3021 Agriculture and Life Sciences Building, Corvallis, OR 97331, United States; Moore Family Center for Whole Grain Foods, Nutrition and Preventive Health, Oregon State University, 212 Milam Hall, Corvallis, OR 97331, United States. Electronic address: Emily.Ho@oregonstate.edu.
authors.forename: Emily
authors.initials: E
authors.lastname: Ho
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000235:genetics; D004625:Embryo, Nonmammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D007328:Insulin / Q000235:genetics; D008670:Metals / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics*; D015032:Zinc / Q000172:deficiency*
chemical_list: D007328:Insulin; D008670:Metals; D029961:Zebrafish Proteins; D015032:Zinc
keywords: Epigenetics; Fitness; Learning; Zebrafish; Zinc deficiency; Zinc homeostasis