FOXM1 Participates in Trophoblast Migration and Early Trophoblast Invasion: potential Role in Blastocyst Implantation

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dc.coverageDOI: 10.3390/ijms25031678
dc.creatorPeñailillo, Reyna
dc.creatorVelásquez, Victoria
dc.creatorAcuña-Gallardo, Stephanie
dc.creatorGarcía, Felipe
dc.creatorSánchez, Mario
dc.creatorNardocci, Gino
dc.creatorIllanes, Sebastián E.
dc.creatorMonteiro, Lara J.
dc.date2024
dc.date.accessioned2025-11-18T19:42:58Z
dc.date.available2025-11-18T19:42:58Z
dc.description<p>Successful implantation requires coordinated migration and invasion of trophoblast cells into a receptive endometrium. Reduced forkhead box M1 (FOXM1) expression limits trophoblast migration and angiogenesis in choriocarcinoma cell lines, and in a rat model, placental FOXM1 protein expression was significantly upregulated in the early stages of pregnancy compared to term pregnancy. However, the precise role of FOXM1 in implantation events remains unknown. By analyzing mice blastocysts at embryonic day (E3.5), we have demonstrated that FOXM1 is expressed as early as the blastocyst stage, and it is expressed in the trophectoderm of the blastocyst. Since controlled oxygen tension is determinant for achieving normal implantation and placentation and a chronic hypoxic environment leads to shallow trophoblast invasion, we evaluated if FOXM1 expression changes in response to different oxygen tensions in the HTR-8/SVneo first trimester human trophoblast cell line and observed that FOXM1 expression was significantly higher when trophoblast cells were cultured at 3% O<sub>2</sub>, which coincides with oxygen concentrations in the uteroplacental interface at the time of implantation. Conversely, FOXM1 expression diminished in response to 1% O<sub>2</sub> that resembles a hypoxic environment in utero. Migration and angiogenesis were assessed following FOXM1 knockdown and overexpression at 3% O<sub>2</sub> and 1% O<sub>2</sub>, respectively, in HTR-8/SVneo cells. FOXM1 overexpression increased transmigration ability and tubule formation. Using a 3D trophoblast invasion model with trophospheres from HTR-8/SVneo cells cultured on a layer of MATRIGEL and of mesenchymal stem cells isolated from menstrual fluid, we observed that trophospheres obtained from 3D trophoblast invasion displayed higher FOXM1 expression compared with pre-invasion trophospheres. Moreover, we have also observed that FOXM1-overexpressing trophospheres increased trophoblast invasion compared with controls. HTR-8/SVneo-FOXM1-depleted cells led to a downregulation of PLK4, VEGF, and MMP2 mRNA expression. Our current findings suggest that FOXM1 participates in embryo implantation by contributing to trophoblast migration and early trophoblast invasion, by inducing transcription activation of genes involved in these processes. Maternal-fetal communication is crucial for trophoblast invasion, and maternal stromal cells may induce higher levels of FOXM1 in trophoblast cells.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/3199f054-3593-4093-8b7f-11418b511fe5
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/52612
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.25 (2024) date: 2024-01-30 nr.3 p.1-17
dc.subjectAnimals
dc.subjectCell Movement
dc.subjectEmbryo Implantation
dc.subjectFemale
dc.subjectForkhead Box Protein M1/genetics
dc.subjectHumans
dc.subjectMice
dc.subjectOxygen/metabolism
dc.subjectPlacenta/metabolism
dc.subjectPregnancy
dc.subjectProtein Serine-Threonine Kinases/metabolism
dc.subjectRats
dc.subjectTrophoblasts/metabolism
dc.titleFOXM1 Participates in Trophoblast Migration and Early Trophoblast Invasion: potential Role in Blastocyst Implantationeng
dc.typeArticleeng
dc.typeArtículospa
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