Tumor necrosis factor-alpha converting enzyme in the human placenta throughout gestation
Tai-Ho Hung1, Szu-Fu Chen, Ching-Chang Hsieh
1Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, Taiwan.
Reproductive Sciences (Thousand Oaks, Calif.)
|February 16, 2008
Summary
Tumor necrosis factor-alpha converting enzyme (TACE) is crucial for placental development, regulating growth factor shedding. Hypoxia increases TACE expression, impacting human pregnancy.
Area of Science:
- Reproductive biology
- Molecular and cellular biology
- Biochemistry
Background:
- Ectodomain shedding of epidermal growth factor receptor ligands is vital for implantation.
- Tumor necrosis factor-alpha converting enzyme (TACE) is implicated as a key sheddase for these ligands.
Purpose of the Study:
- To characterize TACE expression in the human placenta throughout gestation.
- To determine the association between TACE and specific growth factors (TGF-α, HBEGF, AREG).
- To investigate TACE's role in mediating growth factor shedding and the effect of hypoxia on TACE expression.
Main Methods:
- Analysis of 55 human placental villous samples across gestation.
- In vitro studies using villous explant cultures and cytotrophoblastic cells.
- TACE inhibition and gene silencing (small interference RNA) experiments.
- Assessment of TACE mRNA and protein levels under normoxic and hypoxic conditions.
Main Results:
- TACE is continuously expressed in the placenta throughout gestation.
- TACE levels positively correlate with TGF-α, HBEGF, and AREG levels.
- TACE inhibition/silencing reduces HBEGF and AREG shedding.
- Hypoxia significantly increases TACE mRNA and protein expression in placental cells.
Conclusions:
- Oxygen levels regulate TACE expression in the human placenta.
- TACE plays a significant role in placental development during human pregnancy by mediating growth factor shedding.
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