Fidelity of chemical hypoxia models to preeclampsia placental gene-expression profiles

Determine the extent to which cobalt(II) chloride and oxyquinoline-derivative HIF-prolyl hydroxylase inhibitors, when used to chemically induce hypoxia in trophoblast cell models, faithfully recapitulate the complex gene-expression profiles characteristic of preeclampsia placental tissue.

Background

Preeclampsia is closely associated with placental hypoxia and activation of HIF-mediated pathways. In vitro, trophoblast hypoxia is commonly modeled using cobalt(II) chloride or oxyquinoline derivatives that inhibit prolyl hydroxylases and stabilize HIF-1α. However, cobalt(II) chloride is known to have broad off-target effects, while oxyquinoline derivatives are designed to be more selective inhibitors of HIF prolyl hydroxylases.

Despite their widespread use, it is explicitly stated that the field lacks clarity on how well these chemical hypoxia models emulate the complex gene-expression programs observed in preeclamptic placentas. Addressing this uncertainty is important for validating in vitro systems as faithful models of the in vivo trophoblast response in preeclampsia.