7: Placental and renal expression of hypoxic genes in a mouse model of preeclampsia induced by over-expression of SFLT-1

Article Outline

• Objective
• Study design
• Results
• Conclusion
• Copyright

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Objective 

sFlt-1 and placental hypoxia have been shown to be implicated in the etiology of preeclampsia. Our objective was to determine the placental and renal expression of selected genes regulated by hypoxia and involved in angiogenesis in a previously characterized rodent model of preeclampsia induced by over-expression of sFlt-1.

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Study design 

At day 8 of gestation, CD-1 mice were randomly allocated to injection of the adenovirus carrying Flt (1-3) [AdFlt(1-3); 10⁹ PFU], adenovirus carrying mFc as virus control (10⁹ PFU), or saline (n=4-10/group). At day 18 of gestation, the mice were sacrificed; kidneys and placentas were removed, weighed and snap frozen. mRNA expression of hypoxic-inducible factor-1 α (HIF-1α), transforming growth factor β3 (TGFβ3) and glial cells missing 1 (GCM1) was determined using real-time RT-PCR. One-way ANOVA followed by Newman-Keuls post-hoc test were used for statistical analysis (significance: p<0.05).

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Results 

The average placental weight in the sFlt-1 group (0.12±0.006 g) was significantly lower compared with the mFc and saline groups (0.19±0.02 g and 0.192±0.019 g, respectively). In placenta from the sFlt-1 group, HIF1α and TGFβ3 gene expression were significantly increased by 3 and 7 folds, respectively, compared with mFc and saline groups (P<0.05). Placental GCM1 gene expression was significantly decreased by 5 folds in the sFlt-1 group compared with the saline and mFc groups. In the kidney, HIF1α expression was significantly increased by 2 folds in the sFlt-1 group compared with the other 2 groups, while no significant differences were seen in the expressions of TGFβ3 and GCM1.

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Conclusion 

Inhibition of angiogenic factors by sFlt-1 results in a hypoxic placenta, which in turn explains the preeclampsia-like condition previously characterized in this animal model. This effect is possibly mediated via the transcription factor HIF-1α and its downstream target molecule, TGFβ3 which lead to altered GCM1 expression. Further investigation of this mechanism may improve our understanding of preeclampsia.