Zinc Supplementation at the Time of Ethanol Exposure Ameliorates Teratogenicity in Mice

Carey, Luke C.; Coyle, Peter; Philcox, Jeffrey C.; Rofe, Allan M.

doi:10.1111/j.1530-0277.2003.tb02729.x

Cited by 31 publications

(27 citation statements)

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“…Immediately after the first ethanol injection, the third group of mice was given an additional 250 L s.c. injection in the nape of the neck of ZnSO 4 in saline (2.5 g Zn/g). An s.c. Zn injection gives an immediate and consistently reproducible increase in plasma Zn that peaks four-to fivefold normal 2 h after injection and declines to more than 50% of this at 4 h, returning to normal levels (14 mol/L) by 12 h. We have found no evidence that these plasma Zn levels have a detrimental affect on pregnancy outcome (14). Food was removed after the first injection and returned after the second.…”

Section: Methodsmentioning

confidence: 65%

“…Anatomical changes in the hippocampus, including reduced numbers of neurons and abnormal arrangement of hippocampal mossy fibers, have been associated with alcohol exposure during pregnancy (18,33,34). Further research is required with MTϪ/Ϫ mice to demonstrate whether the spatial memory impairments caused by ethanol are associated with an MT-induced Zn deficiency, as previously demonstrated with physical abnormalities (12)(13)(14).…”

Section: Discussionmentioning

confidence: 90%

“…The involvement of Zn deficiency is further supported by findings that the transfer of 65 Zn to the fetus was significantly impaired and the total fetal zinc reduced, after alcohol exposure in MTϩ/ϩ mice (13) and rats (11), but not in MTϪ/Ϫ mice (13). In addition, s.c. Zn treatment at the time of ethanol exposure on GD8 prevents the physical abnormalities caused by ethanol by increasing plasma Zn concentrations up to fivefold during the period of transient Zn deficiency (14). This raises the critical question addressed in the present study of whether s.c. Zn treatment can also prevent cognitive impairments caused by ethanol consumption during early pregnancy.…”

mentioning

confidence: 79%

“…It has been shown that ethanol consumption during pregnancy can also result in eye abnormalities (1,10,12,14) and motor impairments (3). It can be argued that these abnormalities may affect performance in the spatial navigation task.…”

Section: Discussionmentioning

confidence: 99%

“…We have hypothesized that prenatal Zn treatment replenishes the fetal Zn supply, which is transiently depleted due to the induction by alcohol of MT in the mother's liver. As the s.c. Zn injection administered increases plasma Zn levels 5-fold that of normal (14), it is likely that this could offset the sequestration of Zn by induced levels of MT in the mother's liver and maintain relatively normal plasma Zn levels in the period immediately following ethanol exposure. However, the possibility that Zn has MT-independent effects on the developing brain cannot be overlooked.…”

Section: Discussionmentioning

confidence: 99%

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Prenatal Zinc Treatment at the Time of Acute Ethanol Exposure Limits Spatial Memory Impairments in Mouse Offspring

2006

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Zinc (Zn) treatment given together with acute ethanol in early pregnancy has previously been demonstrated to protect against physical birth abnormalities in mice. The current study examined whether this Zn treatment (s.c. injection) can also prevent the more subtle cognitive impairments caused by ethanol exposure in early pregnancy. Pregnant C57BL/6J dams were injected with saline (0.85% wt/vol NaCl) or 25% ethanol (0.015 mL/g body weight) intraperitoneally at 0 and 4 h on gestational d (GD) 8. ZnSO 4 (2.5 g Zn/g at 0 h) treatment was administered by s.c. injection immediately following ethanol treatment. Offspring were randomly selected from litters for each of the three treatment groups and were tested at 55 and 70 d of age using a cross-maze water escape task for spatial learning and memory impairments consecutively. No differences were observed between treatments for the spatial learning task. However, young adult mice exposed to ethanol in utero demonstrated impaired spatial memory, with a decrease in correct trials and increased escape latency and incorrect entry measurements, compared with salinetreated controls. In comparison, offspring given s.c. Zn treatment at the time of ethanol exposure were not cognitively impaired, performing at the same level as control mice in the cross-maze escape task. These findings indicate that critically timed Zn administration can limit spatial memory impairments caused by ethanol exposure in early pregnancy. T he teratogenic nature of ethanol has been well documented in humans and experimental animals (1-3). Consumption of ethanol during pregnancy can produce an array of physical abnormalities, including prenatal and/or postnatal growth deficiency and craniofacial dysmorphology (4). However, cognitive and behavioral impairments, such as deficits in attention, learning, and memory (5) are much more commonly observed in children exposed prenatally to ethanol and hence are more significant and costly to both the individual and community. These outcomes result from diverse maternal drinking patterns, ranging from the episodic ЉbingeЉ of large quantities of ethanol over a short time period to chronic ethanol intake.The mechanisms involved in ethanol-related abnormalities are unclear. Although it is likely that many factors are involved, several lines of evidence support fetal Zn deficiency as a major contributing factor to ethanol teratogenicity. First, an adequate supply of Zn to the fetus is critical during pregnancy (6). In rodents, there are similarities in fetal outcome between prenatal Zn deficiency and prenatal ethanol exposure. These include increased fetal resorptions, low birth weight, and birth abnormalities (7-10). These effects are potentiated during organogenesis (GD 7-12 in rodents, weeks 3-9 in humans), a period during early pregnancy critical for development and cell differentiation.Second, studies in rats (11) and in our laboratory using mice demonstrate that acute ethanol exposure in early pregnancy causes fetal Zn deficiency via the induction of ...

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Section: Methodsmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 90%

mentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prenatal Zinc Treatment at the Time of Acute Ethanol Exposure Limits Spatial Memory Impairments in Mouse Offspring

2006

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Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide

Schreiner

Bell

Scott

2009

Birth Defects Research

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Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development

Uriu‐Adams

Keen

2010

Birth Defects Research Pt B

118

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A large body of evidence supports the concept that human pregnancy outcome is significantly influenced by the nutritional status of the mother. The consumption of "poor diets" has been associated with an increased risk for pregnancy complications, including gross structural birth defects, prematurity, low birth weight, and an increased risk for neurobehavioral and immunological abnormalities after birth. Forty-four years ago, zinc deficiency in mammals was shown to be teratogenic. Maternal zinc deficiency produces effects ranging from infertility and embryo/fetal death, to intrauterine growth retardation and teratogenesis. Postnatal complications of maternal zinc deficiency can also occur, and include behavioral abnormalities, impaired immunocompetence, and an elevated risk for high blood pressure in the offspring. It has been suggested that developmental zinc deficiency in humans can present a significant challenge to the conceptus, increasing the risk for numerous defects. Developmental zinc deficiency can occur through multiple pathways, and the concept that acute phase response-induced changes in maternal zinc metabolism may be a common cause of embryonic and fetal zinc deficiency is presented. Potential mechanisms underlying the teratogenic effects of zinc deficiency are reviewed. The potential value of maternal zinc supplementation in high risk pregnancies is discussed.

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Zinc Supplementation at the Time of Ethanol Exposure Ameliorates Teratogenicity in Mice

Abstract: These findings demonstrate that Zn supplementation at the time of ethanol exposure significantly negates the deleterious effects of ethanol on the fetus.

Cited by 31 publications

References 14 publications

Prenatal Zinc Treatment at the Time of Acute Ethanol Exposure Limits Spatial Memory Impairments in Mouse Offspring

Prenatal Zinc Treatment at the Time of Acute Ethanol Exposure Limits Spatial Memory Impairments in Mouse Offspring

Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide

Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development

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