Cardiac Abnormalities Induced by Zinc Deficiency Are Associated with Alterations in the Expression of Genes Regulated by the Zinc-Finger Transcription Factor GATA-4

Jodie Y. Duffy, G. J. Overmann, Carl L Keen, M. S. Clegg, G. P. Daston

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Zinc (Zn) deficiency during pregnancy results in a wide variety of developmental abnormalities. The objective of this study was to determine if expression of cardiac developmental genes regulated by Zn-finger transcription factors could be modulated during dietary Zn deficiency. Rats were fed 0.5 (low Zn) or 90 (controls) μg Zn/g diet throughout pregnancy. Fetal development was examined and RNA isolated at gestation day (GD) 13 and 20. Cardiac abnormalities were detected at GD 20 in 82% of fetuses from dams fed low Zn diets compared with only 2% in controls. Cardiac developmental gene expression regulated by the Zn-finger transcription factor, GATA-4, was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In GD 13 and 20 hearts, two genes critical for heart development, α-myosin heavy chain (α-MHC) and cardiac troponin I (cTnI), were down-regulated in Zn-deficient fetuses. Expression of α-MHC was 66 and 40% lower at GD 13 and 20, respectively, in fetuses from dams fed low Zn diets compared with fetuses from control dams (p<0.05). Fetal cardiac TnI RNA levels were reduced 40 and 45% at GD 13 and 20 in the Zn-deficient group compared with controls (p<0.05). Fetal cardiac transcript levels of GATA-4 and MHox, a gene regulated by a helix-loop-helix transcription factor, whose expressions are not Zn-dependent, were unaffected by diet. These data indicated that alterations in gene regulation might be an underlying mechanism of cardiac abnormalities. Dysfunction of other Zn-dependent transcription factors may be an integral part of the extensive teratogenesis associated with Zn deficiency.

Original languageEnglish (US)
Pages (from-to)102-109
Number of pages8
JournalBirth Defects Research Part B - Developmental and Reproductive Toxicology
Volume71
Issue number2
DOIs
StatePublished - Apr 2004

Fingerprint

GATA4 Transcription Factor
Zinc Fingers
Zinc
Genes
Gene Expression
Pregnancy
Nutrition
Fetus
Diet
Developmental Genes
Transcription Factors
Dams
Gene expression
RNA
Teratogenesis
Troponin I
Myosin Heavy Chains
Fetal Development
Reverse Transcriptase Polymerase Chain Reaction
Polymerase chain reaction

Keywords

  • Gene regulation
  • Heart development
  • Teratogenesis

ASJC Scopus subject areas

  • Genetics
  • Toxicology
  • Cancer Research

Cite this

Cardiac Abnormalities Induced by Zinc Deficiency Are Associated with Alterations in the Expression of Genes Regulated by the Zinc-Finger Transcription Factor GATA-4. / Duffy, Jodie Y.; Overmann, G. J.; Keen, Carl L; Clegg, M. S.; Daston, G. P.

In: Birth Defects Research Part B - Developmental and Reproductive Toxicology, Vol. 71, No. 2, 04.2004, p. 102-109.

Research output: Contribution to journalArticle

@article{1423ed8ece0b4e3889f4bd634fd4a1e0,
title = "Cardiac Abnormalities Induced by Zinc Deficiency Are Associated with Alterations in the Expression of Genes Regulated by the Zinc-Finger Transcription Factor GATA-4",
abstract = "Zinc (Zn) deficiency during pregnancy results in a wide variety of developmental abnormalities. The objective of this study was to determine if expression of cardiac developmental genes regulated by Zn-finger transcription factors could be modulated during dietary Zn deficiency. Rats were fed 0.5 (low Zn) or 90 (controls) μg Zn/g diet throughout pregnancy. Fetal development was examined and RNA isolated at gestation day (GD) 13 and 20. Cardiac abnormalities were detected at GD 20 in 82{\%} of fetuses from dams fed low Zn diets compared with only 2{\%} in controls. Cardiac developmental gene expression regulated by the Zn-finger transcription factor, GATA-4, was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In GD 13 and 20 hearts, two genes critical for heart development, α-myosin heavy chain (α-MHC) and cardiac troponin I (cTnI), were down-regulated in Zn-deficient fetuses. Expression of α-MHC was 66 and 40{\%} lower at GD 13 and 20, respectively, in fetuses from dams fed low Zn diets compared with fetuses from control dams (p<0.05). Fetal cardiac TnI RNA levels were reduced 40 and 45{\%} at GD 13 and 20 in the Zn-deficient group compared with controls (p<0.05). Fetal cardiac transcript levels of GATA-4 and MHox, a gene regulated by a helix-loop-helix transcription factor, whose expressions are not Zn-dependent, were unaffected by diet. These data indicated that alterations in gene regulation might be an underlying mechanism of cardiac abnormalities. Dysfunction of other Zn-dependent transcription factors may be an integral part of the extensive teratogenesis associated with Zn deficiency.",
keywords = "Gene regulation, Heart development, Teratogenesis",
author = "Duffy, {Jodie Y.} and Overmann, {G. J.} and Keen, {Carl L} and Clegg, {M. S.} and Daston, {G. P.}",
year = "2004",
month = "4",
doi = "10.1002/bdrb.20004",
language = "English (US)",
volume = "71",
pages = "102--109",
journal = "Teratogenesis Carcinogenesis and Mutagenesis",
issn = "1542-9733",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Cardiac Abnormalities Induced by Zinc Deficiency Are Associated with Alterations in the Expression of Genes Regulated by the Zinc-Finger Transcription Factor GATA-4

AU - Duffy, Jodie Y.

AU - Overmann, G. J.

AU - Keen, Carl L

AU - Clegg, M. S.

AU - Daston, G. P.

PY - 2004/4

Y1 - 2004/4

N2 - Zinc (Zn) deficiency during pregnancy results in a wide variety of developmental abnormalities. The objective of this study was to determine if expression of cardiac developmental genes regulated by Zn-finger transcription factors could be modulated during dietary Zn deficiency. Rats were fed 0.5 (low Zn) or 90 (controls) μg Zn/g diet throughout pregnancy. Fetal development was examined and RNA isolated at gestation day (GD) 13 and 20. Cardiac abnormalities were detected at GD 20 in 82% of fetuses from dams fed low Zn diets compared with only 2% in controls. Cardiac developmental gene expression regulated by the Zn-finger transcription factor, GATA-4, was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In GD 13 and 20 hearts, two genes critical for heart development, α-myosin heavy chain (α-MHC) and cardiac troponin I (cTnI), were down-regulated in Zn-deficient fetuses. Expression of α-MHC was 66 and 40% lower at GD 13 and 20, respectively, in fetuses from dams fed low Zn diets compared with fetuses from control dams (p<0.05). Fetal cardiac TnI RNA levels were reduced 40 and 45% at GD 13 and 20 in the Zn-deficient group compared with controls (p<0.05). Fetal cardiac transcript levels of GATA-4 and MHox, a gene regulated by a helix-loop-helix transcription factor, whose expressions are not Zn-dependent, were unaffected by diet. These data indicated that alterations in gene regulation might be an underlying mechanism of cardiac abnormalities. Dysfunction of other Zn-dependent transcription factors may be an integral part of the extensive teratogenesis associated with Zn deficiency.

AB - Zinc (Zn) deficiency during pregnancy results in a wide variety of developmental abnormalities. The objective of this study was to determine if expression of cardiac developmental genes regulated by Zn-finger transcription factors could be modulated during dietary Zn deficiency. Rats were fed 0.5 (low Zn) or 90 (controls) μg Zn/g diet throughout pregnancy. Fetal development was examined and RNA isolated at gestation day (GD) 13 and 20. Cardiac abnormalities were detected at GD 20 in 82% of fetuses from dams fed low Zn diets compared with only 2% in controls. Cardiac developmental gene expression regulated by the Zn-finger transcription factor, GATA-4, was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In GD 13 and 20 hearts, two genes critical for heart development, α-myosin heavy chain (α-MHC) and cardiac troponin I (cTnI), were down-regulated in Zn-deficient fetuses. Expression of α-MHC was 66 and 40% lower at GD 13 and 20, respectively, in fetuses from dams fed low Zn diets compared with fetuses from control dams (p<0.05). Fetal cardiac TnI RNA levels were reduced 40 and 45% at GD 13 and 20 in the Zn-deficient group compared with controls (p<0.05). Fetal cardiac transcript levels of GATA-4 and MHox, a gene regulated by a helix-loop-helix transcription factor, whose expressions are not Zn-dependent, were unaffected by diet. These data indicated that alterations in gene regulation might be an underlying mechanism of cardiac abnormalities. Dysfunction of other Zn-dependent transcription factors may be an integral part of the extensive teratogenesis associated with Zn deficiency.

KW - Gene regulation

KW - Heart development

KW - Teratogenesis

UR - http://www.scopus.com/inward/record.url?scp=2342568440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342568440&partnerID=8YFLogxK

U2 - 10.1002/bdrb.20004

DO - 10.1002/bdrb.20004

M3 - Article

C2 - 15098203

AN - SCOPUS:2342568440

VL - 71

SP - 102

EP - 109

JO - Teratogenesis Carcinogenesis and Mutagenesis

JF - Teratogenesis Carcinogenesis and Mutagenesis

SN - 1542-9733

IS - 2

ER -