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.

Influence of Commercial and Laboratory Diets on Growth, Body Composition, and Reproduction in the ZebrafishDanio rerio

“…11 As observed in mammals, specific nutrients and dietary ingredients, or the lack thereof, can potentially alter physiology, behavior, and/or molecular pathways in zebrafish, [12][13][14][15][16][17][18][19][20][21][22][23][24][25] whereas other researches suggested that nutrient content of diets fed to adult zebrafish can even influence the development and health of their offspring. [26][27][28][29][30][31] All these evidences suggest that for zebrafish, diet is an important environmental factor that can potentially compromise and confound outcomes related to the question of study; Therefore, a lack of nutritional control in zebrafish laboratories could affect the interpretation of both past and future research. 32 At present, a wide variety of commercial diets is utilized in zebrafish research laboratories, and in some cases, include live animal supplementation (paramecia, rotifers, and brine shrimp) during early or other life stages.…”

Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development

“…All adult animals were fed standard lab diet (Gemma Micro. Skretting, Tooele, France) until 8 weeks post fertilization when they were moved to clean enclosures, randomized to either zinc deficient or zinc adequate diets, and housed at densities of ~6 fish / liter as previously described [ 34 ]. The zebrafish diets were produced as previously described [ 34 ].…”

“…Skretting, Tooele, France) until 8 weeks post fertilization when they were moved to clean enclosures, randomized to either zinc deficient or zinc adequate diets, and housed at densities of ~6 fish / liter as previously described [ 34 ]. The zebrafish diets were produced as previously described [ 34 ]. Feeding volumes for all feeds were ~5% body weight / day, or until satiation, given over 2–3 feedings in a day depending on life stage.…”

“…Importantly, like humans, zebrafish require dietary zinc intake and have similar regulatory mechanisms that maintain zinc homeostasis including its uptake and intracellular distribution by zinc importers ( zip / slc39 ) and zinc exporters ( znt / slc30 ) [ 33 ]. We recently developed a zinc deficient zebrafish diet and demonstrated the embryos from zinc deficient zebrafish parents are also zinc deficient, and this is associated with changes in gene expression, decreased physical activity, and a 2-fold increase in mortality in the embryos [ 34 ].…”

Current basis and future directions of zebrafish nutrigenomics

“…By day 14, most of the genes impacted by zinc supplementation returned to basal expression levels. Beaver et al provided zinc-deficient diets to zebrafish and looked at the impact on their offspring [93]. Embryos produced by those receiving the zinc-deficient diets had increased embryonic mortality and malformations of the snout and eyes.…”