Placental Tissue Calcification and Its Molecular Pathways in Female Patients with Late-Onset Preeclampsia
Miguel A. Ortega,
Tatiana Pekarek,
Diego De Leon-Oliva,
Diego Liviu Boaru,
Oscar Fraile-Martinez,
Cielo García-Montero,
Julia Bujan,
Leonel Pekarek,
Silvestra Barrena-Blázquez,
Raquel Gragera,
Patrocinio Rodríguez-Benitez,
Mauricio Hernández-Fernández,
Laura López-González,
Raul Díaz-Pedrero,
Ángel Asúnsolo,
Melchor Álvarez-Mon,
Natalio García-Honduvilla,
Miguel A. Saez,
Juan A. De León-Luis,
Coral Bravo
Affiliations
Miguel A. Ortega
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Tatiana Pekarek
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Diego De Leon-Oliva
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Diego Liviu Boaru
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Oscar Fraile-Martinez
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Cielo García-Montero
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Julia Bujan
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Leonel Pekarek
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Silvestra Barrena-Blázquez
Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
Raquel Gragera
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Patrocinio Rodríguez-Benitez
Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain
Mauricio Hernández-Fernández
Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Laura López-González
Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
Raul Díaz-Pedrero
Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
Ángel Asúnsolo
Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
Melchor Álvarez-Mon
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Natalio García-Honduvilla
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Miguel A. Saez
Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Juan A. De León-Luis
Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain
Coral Bravo
Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain
Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks’ gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and β-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.