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 language | English (US) |
|---|---|
| Pages (from-to) | 102-109 |
| Number of pages | 8 |
| Journal | Birth Defects Research Part B - Developmental and Reproductive Toxicology |
| Volume | 71 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 2004 |
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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 journal › Article
}
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 -