Altered maternal zinc metabolism following exposure to diverse developmental toxicants

Taubeneck, Marie W.; Daston, George P.; Rogers, John M.; Keen, Carl L.

doi:10.1016/0890-6238(94)90064-7

Cited by 85 publications

(49 citation statements)

References 37 publications

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“…4). It is well established that maternal hepatic MT induction results in an accumulation of Zn within the liver to the detriment of plasma Zn concentration (see [220] and arsenic are known inducers of MT, and have been shown to impair the transfer of Zn from mother to fetus when administered during the organogenic period [223][224][225][226][227][228]. Furthermore, the types of fetal abnormalities resulting from these teratogenic insults are very similar to those caused by Zn deficiency itself, thus implying, at least to some extent, a common underlying etiology [220].…”

Section: Mt and Pregnancymentioning

confidence: 99%

Metallothionein: the multipurpose protein

Coyle¹,

Philcox²,

Lc³

et al. 2002

Cellular and Molecular Life Sciences (CMLS)

1,160

803

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Metallothioneins (MTs) are intracellular, low molecular, low molecular weight, cysteine-rich proteins. Ubiquitous in eukaryotes, MTs have unique structural characteristics to give potent metal-binding and redox capabilities. A primary role has not been identified, and remains elusive, as further functions continue to be discovered. The most widely expressed isoforms in mammals, MT-1 and MT-2, are rapidly induced in the liver by a wide range of metals, drugs and inflammatory mediators. In teh gut and pancreas, MT responds mainly to Zn status. A brain isoform, MT-3, has a specific neuronal growth inhibitory activity, while MT-1 and MT-2 have more diverse functions related to their thiolate cluster structure. These include involvement in Zn homeostasis, protection against heavy metal (especially Cd) and oxidant damage, and metabolic regulation via Zn donation, sequestration and/or redox control. Use of mice with altered gene expression has enhance our understanding of the multifaceted role of MT, emphasised in this review.

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Section: Mt and Pregnancymentioning

confidence: 99%

Metallothionein: the multipurpose protein

Coyle¹,

Philcox²,

Lc³

et al. 2002

Cellular and Molecular Life Sciences (CMLS)

1,160

803

View full text Add to dashboard Cite

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“…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 the Zn binding protein metallothionein (MT) I and II in the maternal liver. Following increased expression of MT, Zn is sequestered by MT and redistributed to the liver, causing plasma Zn concentrations to decrease by up to 65% over 16 h. This limitation in fetal Zn supply from the maternal plasma is associated with an increased incidence of physical abnormalities in ethanoltreated MTϩ/ϩ mice (27%) compared with saline-treated mice (6.4%).…”

mentioning

confidence: 99%

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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“…This well-studied mode of action is initiated by maternal tissue damage, which then induces an acute phase response and subsequent induction of maternal hepatic metallothionein leading to extensive zinc sequestration in maternal liver. Ultimately, the transfer of zinc to the embryo is reduced and a zinc deficiency in the conceptus ensues (Taubeneck et al, 1994). WEC was crucial in the elucidation of this mode of action by showing that the parent compounds had no effects on embryo development, whereas zinc-deficient serum was deleterious.…”

Section: Nutritional Factors In Teratogenesismentioning

confidence: 99%

Whole embryo culture: a “New” technique that enabled decades of mechanistic discoveries

Ellis-Hutchings

Carney

2010

Birth Defects Research Pt B

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Denis New's development of the rodent whole embryo culture (WEC) method in the early 1960s was a groundbreaking achievement that gave embryologists and teratologists an unprecedented degree of access to the developing postimplantation rodent embryo. In the five decades since its development, WEC has enabled detailed investigations into the regulation of normal embryo development as well as a plethora of research on mechanisms of teratogenesis as induced by a wide range of agents. In addition, WEC is one of the few techniques that has been validated for use in teratogenicity screening of drugs and chemicals. In this review, we retrace the steps leading to New's development of WEC, and highlight many examples in which WEC played a crucial role leading to important discoveries in teratological research. The impact of WEC on the field of teratology has been enormous, and it is anticipated that WEC will remain a preferred tool for teratologists and embryologists seeking to interrogate embryo development for many years to come.

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Altered maternal zinc metabolism following exposure to diverse developmental toxicants

Cited by 85 publications

References 37 publications

Metallothionein: the multipurpose protein

Metallothionein: the multipurpose protein

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

Whole embryo culture: a “New” technique that enabled decades of mechanistic discoveries

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