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

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% O2, which coincides with oxygen concentrations in the uteroplacental interface at the time of implantation. Conversely, FOXM1 expression diminished in response to 1% O2 that resembles a hypoxic environment in utero. Migration and angiogenesis were assessed following FOXM1 knockdown and overexpression at 3% O2 and 1% O2, 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.

Suplementación prenatal con omega 3 y su efecto en complicaciones durante el embarazo / Effect of prenatal omega 3 supplementation on pregnancy outcomes

Durante los últimos años se ha incentivado la suplementación con omega 3 durante el embarazo principalmente debido a la evidencia que mostraría beneficios en el desarrollo neuronal y visual del hijo en gestación, y a la prevención de patologías obstétricas asociadas a un aumento de la morbi-mortalidad perinatal. Los ácidos grasos poliinsaturados (PUFAs) omega 3, específicamente el ácido eicosapentaenoico (EPA) y el ácido docosahexaenoico (DHA), poseen propiedades antiinflamatorias, vasodilatadoras, además de propiedades anti-agregantes, las cuales han estimulado el uso de PUFAs en la prevención de enfermedades cardiovasculares. En esta revisión detallamos los efectos de la suplementación con omega 3 en diferentes aspectos del embarazo tales como la prevención del parto prematuro, preeclampsia, depresión post-parto y mejora del metabolismo durante la diabetes gestacional. Si bien existen diversos ensayos clínicos randomizados que estudian la suplementación con omega 3 durante la gestación, la evidencia sigue siendo no concluyente, debido a la variabilidad de las dosis y tiempo de administración. Ciertamente, un mayor número de estudios de calidad son necesarios para determinar el real impacto de la suplementación con omega 3 durante la gestación en la prevención de patologías obstétricas(AU)

During pregnancy, omega 3 supplementation has raised its popularity due to evidence that it would show not only benefits in the neural and visual development of the unborn child, but also in the prevention of obstetrical pathologies associated with of perinatal morbidity and mortality. Omega 3 polyunsaturated fatty acids (PUFAs), specifically, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), possess anti-inflammatory, vasodilatory and anti-aggregating properties, which have led to the use of PUFAs in the prevention of cardiovascular diseases. In this review, we detail the effects of omega 3 supplementation on different aspects of pregnancy such as prevention of preterm birth, pre-eclampsia, postpartum depression, and improved metabolism during gestational diabetes. Although there are several randomized clinical trials using omega-3 supplementation during pregnancy, the evidence remains inconclusive, due to variability in dosage and administration time. Certainly, a greater number of high-quality studies including randomized clinical trials are necessary to determine the impact of omega 3 supplementation during pregnancy in the prevention of obstetric pathologies(AU)