Role of growth factors and other placental signals in extravillous trophoblast cell function

A successful pregnancy crucially depends on well-regulated extravillous trophoblast migration and invasion. Maternally expressed gene 3 (MEG3) is a long noncoding RNA that plays an important role in regulating trophoblast cells cell function. As previously reported, the expression of MEG3 was reduced in preeclampsia, and downregulation of MEG3 could suppress trophoblast cells migration and promote its apoptosis. However, the downstream regulatory mechanism of MEG3 remains unknown. As reported, MEG3 could inhibit cell proliferation in endometrial carcinoma by regulating Notch signaling. Our previous studies have demonstrated that Notch1 is downregulated in preeclampsia and that inhibiting the expression of Notch1 could promote trophoblast cell apoptosis. Therefore, this study was designed to investigate the role of MEG3 and its the relationship with Notch1 in trophoblasts. In this study, the mRNA expression levels of both MEG3 and Notch1 were decreased in preeclampsia placenta (n = 15) compared to the normal samples (n = 15). Exogenous upregulation and downregulation of MEG3 in HTR8/SVneo cells were performed to investigate the role of MEG3 in cell biological behavior and its effects on Notch1 expression. The results showed that MEG3 enhancement promoted trophoblast cell migration and invasion and inhibited cell apoptosis. Downregulation of MEG3 elicited the opposite results. Associated factors, such as matrix metalloproteinases 2 (MMP2), BAX, and Bcl-2, were examined at the mRNA and protein levels. Our study demonstrated that MEG3 could regulate Notch1 expression to modulate trophoblast cell migration, invasion, and apoptosis, which may represent the molecular mechanism of poor placentation during preeclampsia.

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The involvement of eukaryotic translation initiation factor 4E in extravillous trophoblast cell function

Placenta ◽

10.1016/j.placenta.2012.06.004 ◽

2012 ◽

Vol 33 (9) ◽

pp. 717-724 ◽

Cited By ~ 15

Author(s):

E. Kitroser ◽

M. Pomeranz ◽

G. Epstein Shochet ◽

A. Fishman ◽

L. Drucker ◽

...

Keyword(s):

Translation Initiation ◽

Cell Function ◽

Trophoblast Cell ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Extravillous Trophoblast ◽

Eukaryotic Translation Initiation Factor ◽

Eukaryotic Translation ◽

Eukaryotic Translation Initiation

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Role of Interleukin 8 in Uterine Natural Killer Cell Regulation of Extravillous Trophoblast Cell Invasion

Placenta ◽

10.1016/j.placenta.2010.04.012 ◽

2010 ◽

Vol 31 (7) ◽

pp. 595-601 ◽

Cited By ~ 46

Author(s):

L.G. De Oliveira ◽

G.E. Lash ◽

C. Murray-Dunning ◽

J.N. Bulmer ◽

B.A. Innes ◽

...

Keyword(s):

Natural Killer Cell ◽

Natural Killer ◽

Cell Invasion ◽

Killer Cell ◽

Trophoblast Cell ◽

Interleukin 8 ◽

Extravillous Trophoblast ◽

Cell Regulation ◽

Uterine Natural Killer

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Genome Modifications Involved in Developmental Programs of the Placental Trophoblast

10.5772/intechopen.97247 ◽

2021 ◽

Author(s):

Tatiana G. Zybina

Keyword(s):

Cell Differentiation ◽

Gene Copy Number ◽

Histone Variants ◽

Mitotic Division ◽

Trophoblast Cell ◽

Extravillous Trophoblast ◽

Gene Copy ◽

Trophoblast Cells ◽

Genome Modifications

The placental trophoblast cells give an example of profound genome modifications that lead to whole-genome multiplication, aneuploidy, under-replication of some genes or their clusters as well as, by contrast, gene amplification. These events are included into program of differentiation of functionally different cell lineages. In some cases the trophoblast cell differentiation involves depolyploidization achieved by non-mitotic division. Aneuploidy may be also accounted for by the unusual mitoses characteristic of Invertebrates and plants; in mammalian it may result from hypomethylation of centromere chromosome regions. The giant (endopolyploid) trophoblast cells organization includes “loose nucleosomes” accounted for by the non-canonical histone variants, i.e. H2AX, H2AZ, and H3. 3 . In the human extravillous trophoblast cells that, like murine TGC, invade endometrium, there occured significant changes of methylation as compared to non-invasive trophoblast cell populations . Meantime, some genes show hypermethylation connected with start of trophoblast lineages specification. Thus, despite the limited possibilities of chromosome visualization trophoblast cells represent an interesting model to investigate the role of modification of gene copy number and their expression that is important for the normal or abnormal cell differentiation.

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108. FUNCTIONAL ROLE OF HtrA3 IN TROPHOBLAST CELL INVASION DURING HUMAN PLACENTAL DEVELOPMENT

Reproduction Fertility and Development ◽

10.1071/srb09abs108 ◽

2009 ◽

Vol 21 (9) ◽

pp. 27

Author(s):

H. Singh ◽

G. Nie

Keyword(s):

Cell Invasion ◽

Stromal Cells ◽

Functional Role ◽

First Trimester ◽

Trophoblast Cell ◽

Extravillous Trophoblast ◽

Placental Development ◽

Decidual Cells

Controlled invasion of extravillous trophoblast (EVT) through the maternal decidua is important for placental development and function. Serine protease HtrA3 is highly expressed in the decidual cells in the late secretory phase of the menstrual cycle and throughout pregnancy. It is highly expressed in first trimester in most trophoblast cell types, but not in the invading interstitial trophoblast. HtrA3 and its family members are down-regulated in a number of cancers and are proposed as tumor-suppressors. We hypothesized that HtrA3 is an inhibitor of trophoblast invasion and is down-regulated in invading EVTs, while up-regulation of decidual HtrA3 controls the process. The current study investigated HtrA3 expression in human endometrial stromal cells (HESC) during decidualization in vitro and whether HtrA3 inhibits EVT cell invasion. Stromal cells isolated from human endometrium were decidualized in vitro with estrogen, progesterone and cAMP. Quantitative RT-PCR and western showed HtrA3 mRNA and protein expression was significantly increased in decidualized HESC compared to controls. Indirect immunofluorescence showed homogeneous pattern and increase in intensity of HtrA3 staining in decidualized HESC compared to non-decidualized cells. HTR-8 cells derived from first trimester of pregnancy EVT showed higher levels of HtrA3 mRNA expression compared to other human choriocarcinoma cell lines (AC-1M88, AC-1M32, JEG-3 and BeWo). Both intracellular and extracellular HtrA3 staining was observed in HTR8 cells. Functional role of HtrA3 in cell invasion was determined in HTR-8 cells using an in vitro invasion assay. Exogenous addition of mutant HtrA3 (inhibitor) resulted in a significant increase in HTR-8 cells invading through matrigel coated membrane compared with controls. TGFβ-1 (as positive control) completely inhibited invasion of HTR-8 cells. HtrA3 is tightly regulated during decidualization of HESC in vitro. Inhibition of HtrA3 activity in trophoblastic HTR-8 cells increased invasiveness supporting its functional role during placental development.

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