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Introduction The development of placenta plays a central role in determining the outcome of pregnancy. Extravillous trophoblast invasion is a fundamental component of human placentation. However, the transcriptional networks responsible for controlling the extent of trophoblast invasion are not well defined. Trophoblast cells are often compared to highly invasive carcinoma cells due to their capacity to proliferate and invade and to exhibit similar gene expression signatures. Thus, the transcriptional regulation of genes associated with cancer metastasis and trophoblast invasion may also be shared. The transcription factor forkhead box M1 (FOXM1), which is one of a few genes shown to be upregulated during early cancer development, possibly fits this scenario. FOXM1 has been shown to play a crucial role in the regulation of cell proliferation, cell cycle progression, angiogenesis, metastasis and DNA damage repair. Objective our objective in this study was to evaluate the role of FOXM1 in normal placental development. Method To evaluate the expression of FOXM1 throughout pregnancy Sprague Dawley dams were sacrificed at E14, E15, E18, E19 and E20 and protein and total RNA was isolated from one placenta per dam. Changes in placental protein expression were analyzed by western blot and mRNA expression was analyzed by qPCR. The influence of FOXM1 on trophoblast proliferation and migration was evaluated by Sulforhodamine B colorimetric (SRB) assay and wound healing assay, respectively, in JEG cell lines following silencing of FOXM1 via RNA interference under 21%, 8% and 3% oxygen conditions. Results The transcription regulator FOXM1 was expressed during early-mid gestation (E14) but its expression decreased as gestational age increased (E14 to E18 there was a decrease in 0.29 fold and E14 to E21 0.04 fold). Compared to trophoblast cells expressing control non-specific siRNA, FOXM1 knockdown resulted in a significant reduction of migration at 21%, 8% and 3% O 2 , whereas silencing of FOXM1 slows down the proliferation of JEG-3 cells at 21% O 2 but it does not alter its proliferative capacity at 8% or 3% O 2 . Conclusions Our data is suggestive that FOXM1 modulates trophoblast migration but not proliferative potential at 8% and 3% O 2 , which coincides with oxygen tension in the placenta in early pregnancy and the results of the rat placenta indicate that FOXM1 may play a role in early placentation events. However, more studies are required to fully understand the exact role of FOXM1 in placenta development. |
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