Preeclampsia remains one of the most formidable complications of human pregnancy, affecting 2–8% of pregnancies and accounting for substantial maternal and fetal morbidity. Although its clinical manifestations—hypertension, proteinuria, and edema—appear in the third trimester, the disorder is initiated early in pregnancy. Its origin is attributed to defective invasion of trophoblast cells, a step indispensable to the establishment of the feto-maternal circulation. During the first trimester, placentation occurs in an initially hypoxic environment; around the ninth or tenth week of gestation, the rise in oxygen tension coincides with the switch of trophoblasts from a proliferative to an invasive phenotype. The protein kinase CK2, a ubiquitous enzyme associated with the control of cell invasion and with adaptive responses to oxidative stress, had never previously been investigated in this context. Composed of a catalytic subunit (CK2α) and a regulatory subunit (CK2β), it was the subject of this first characterization in normal and preeclamptic pregnancies.
To explore its role, the authors combined several levels of analysis: distinct clinical cohorts derived from early pregnancies (n = 24), preeclampsia cases (n = 23), and age-matched controls (n = 28); trophoblast cell lines studied in two-dimensional and three-dimensional culture; ex vivo placental explants; and murine models of preeclampsia, notably the STOX1 and EG-VEGF models. The clinical controls were drawn from non-preeclamptic patients who had delivered preterm for other reasons, a limitation the authors themselves emphasize, as these patients were not entirely normal.
The work establishes that CK2 is more strongly expressed at the end of the first trimester, a period coinciding with the rise in placental oxygen tension, and that it is localized mainly in differentiated trophoblasts. Inhibition of its enzymatic activity reduces trophoblast proliferation, migration, invasion, and syncytialization. In human preeclamptic placentas, CK2 activity and the CK2α/CK2β protein ratio were increased, whereas this ratio remains stable throughout a normal pregnancy—underscoring the importance of a stoichiometric balance between the two subunits. This profile was confirmed in pregnant mice and was accentuated in murine models of preeclampsia, with the imbalance affecting principally the CK2α subunit.
These findings demonstrate that CK2 plays an essential role in the establishment of the feto-maternal circulation and that its dysregulation is associated with the development of preeclampsia. The authors propose that the increase in its activity could constitute a compensatory mechanism intended to support the progression of pregnancy, while acknowledging that further investigation is still needed to determine whether this dysregulation is a cause or a consequence of gestational pathologies.