Reduced FOXM1 Expression Limits Trophoblast Migration and Angiogenesis and Is Associated With Preeclampsia

Autor: Eric Lam, Sebastian E. Illanes, Pía Venegas, Stephanie Acuña-Gallardo, Manuel Varas-Godoy, Marianela Sanchez, Valentina Herrera, Lara J. Monteiro, Sofia Cubillos
Přispěvatelé: Medical Research Council (MRC)
Rok vydání: 2019
Předmět:
Vascular Endothelial Growth Factor A
0301 basic medicine
Umbilical Veins
Angiogenesis
HYPOXIA
OXYGEN
Rats
Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
Pre-Eclampsia
Cell Movement
Pregnancy
trophoblast invasion
implantation
Reproductive Biology
Gene knockdown
030219 obstetrics & reproductive medicine
Neovascularization
Pathologic
Chemistry
Obstetrics & Gynecology
Obstetrics and Gynecology
Transfection
CANCER
Trophoblasts
Oxygen tension
Vascular endothelial growth factor
DIFFERENTIATION
medicine.anatomical_structure
embryonic structures
Female
Life Sciences & Biomedicine
TRANSCRIPTION FACTOR FOXM1
placentation
Cell Line
preeclampsia
Andrology
03 medical and health sciences
Downregulation and upregulation
medicine
Animals
RNA
Messenger
Obstetrics & Reproductive Medicine
Science & Technology
Forkhead Box Protein M1
FOXM1
Endothelial Cells
Trophoblast
Placentation
030104 developmental biology
ENDOTHELIAL GROWTH-FACTOR
CELLS
ONSET
1114 Paediatrics and Reproductive Medicine
Zdroj: Reproductive Sciences
Artículos CONICYT
CONICYT Chile
instacron:CONICYT
ISSN: 1933-7205
1933-7191
Popis: Trophoblast cells are often compared to highly invasive carcinoma cells due to their capacity to proliferate in hypoxic conditions and to exhibit analogous vascular, proliferative, migratory, and invasive capacities. Thus, genes that are important for tumorigenesis, such as forkhead box M1 ( FOXM1) may also be involved in processes of trophoblast invasion. Indeed, we found Foxm1 protein and messenger RNA (mRNA) levels decreased as gestational age increased in rat's placentae. Accordingly, when mimicking early placental events in vitro, protein and mRNA expression of FOXM1 increased from 21% to 8% O2, reaching its highest expression at 3% oxygen tension, which reflects early implantation environment, and dropping to very low levels at 1% O2. Remarkably, FOXM1 silencing in JEG-3 cells was able to significantly decrease migration by 27.9%, in comparison with those cells transfected with control siRNA. Moreover, angiogenesis was compromised when conditioned media (CM) from FOXM1-siRNA -JEG-3 (3% O2) was added to human umbilical vein endothelial cells (HUVEC) cells; however, when CM of JEG-3 cells overexpressing FOXM1 at 1% O2 was added, the ability of HUVEC to form tubule networks was restored. Additionally, quantitative real-time polymerase chain reaction (PCR) assays of FOXM1 knockdown and overexpression experiments in JEG-3 cells revealed that the depletion of FOXM1 at 3% O2 and overexpression of FOXM1 at 1% O2 led to downregulation and upregulation of vascular endothelial growth factor transcriptional (VEGF) levels, respectively. Conversely, we also observed deregulation of FOXM1 in placentae derived from pregnancies complicated by preeclampsia (PE). Therefore, we demonstrate that FOXM1 may be a new regulatory protein of early placentation processes and that under chronic hypoxic conditions (1% O2) and in patients with severe PE, its levels decrease.
Databáze: OpenAIRE
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