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Dual specificity phosphatase 9 (DUSP9) expression is down-regulated in the severe pre-eclamptic placenta
M J Czikk1, S Drewlo, D Baczyk
1Department of Obstetrics & Gynaecology, Mount Sinai Hospital, 600 University Ave, Toronto, ON, Canada M5G 1X5. mczikk@mtsinai.on.ca
Placenta
|January 2, 2013
Summary
Dual specificity phosphatase 9 (DUSP9) is suppressed in pre-eclampsia, potentially due to hypoxia. This finding offers insights into placental insufficiency and its associated pregnancy complications.
Area of Science:
- Reproductive biology
- Molecular genetics
- Perinatal medicine
Background:
- Placental insufficiency underlies serious pregnancy conditions like intrauterine growth restriction (IUGR) and pre-eclampsia.
- Mouse studies show Dual Specificity Phosphatase 9 (DUSP9) is vital for placental development, with knockouts exhibiting growth restriction and placental phenotypes mirroring human conditions.
- Understanding DUSP9's role in human pregnancy is crucial for addressing placental insufficiency.
Purpose of the Study:
- To investigate DUSP9 expression patterns in normal human pregnancy.
- To characterize DUSP9 expression in placentas affected by severe IUGR and/or pre-eclampsia.
- To explore potential epigenetic regulation and the impact of hypoxia on DUSP9.
Main Methods:
- Quantitative RT-PCR, immunohistochemistry, and Western blotting were used to assess DUSP9 gene and protein levels throughout gestation and in pathological pregnancies.
- DUSP9 promoter methylation was analyzed in placentas to examine epigenetic influences.
- In vitro studies involved DUSP9 silencing RNA treatment in first-trimester villous explants and BeWo cells, alongside hypoxic culture conditions.
Main Results:
- DUSP9 expression was detected in villous trophoblast and decreased with gestational progression.
- Significantly lower DUSP9 protein levels were observed in severe pre-eclamptic placentas compared to those with severe IUGR.
- Hypoxic conditions (3% oxygen) significantly reduced DUSP9 expression in vitro, and DUSP9 silencing RNA decreased its expression in placental cells and explants, with a trend towards increased ERK1/2 phosphorylation.
Conclusions:
- DUSP9 protein is markedly suppressed in severe pre-eclampsia, but not in severe IUGR.
- This suppression is potentially linked to the chronic hypoxic environment characteristic of pre-eclampsia.
- Further research is warranted to elucidate the precise mechanisms and clinical implications of DUSP9 dysregulation in placental insufficiency.
