Trophoblast Invasion and Placentation: Molecular Mechanisms and Regulation

Brûle, Frédéric van den; Berndt, Sarah; Simon, Nadine; Coulon, C.; Goarant, Jeanne Le; Munaut, Carine; Noël, Agnès; Frankenne, Françis; Foidart, Jean‐Michel

doi:10.1159/000087833

Cited by 26 publications

(25 citation statements)

References 107 publications

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“…The formation of a functional placenta requires the extensive, although well-controlled, invasion of trophoblast cells through the stromal compartment [5]. Therefore, the mechanisms controlling this process involve both the signals that promote and limit trophoblast invasion.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

et al. 2012

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Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion.

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Section: Discussionmentioning

confidence: 99%

“…Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the stroma, and requires the action of tissue remodelling enzymes [5]. Metalloproteinases (MMPs) are a family of zinc-dependent enzymes that play a key role in degrading components of the extracellular matrix (ECM).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

et al. 2012

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“…The disease is manifest in the third trimester of pregnancy with a wide variety of maternal symptoms, of which hypertension, proteinuria, and edema are late manifestations of a multifactorial, multisystemic disorder initiated in early pregnancy [2] . Although the precise etiology of PE remains unknown, increasing evidence suggests that abnormal trophoblast invasion is considered the core feature of this disease [3,4] . For instance, trophoblastic remodeling of the uterine spiral arterioles is diminished in virtually all cases of PE [5,6] compared to normal pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Proteins Differentially Expressed in Preeclamptic Trophoblasts

Sun

Yang

et al. 2007

Gynecol Obstet Invest

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Aims: To identify differential trophoblastic proteins associated with preeclampsia (PE) by proteomic analysis. Methods: We isolated and purified placental trophoblasts from normotensive pregnant women and patients with PE by a continuous Percoll gradient. The expression of proteins was determined by sliver staining after two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Proteins of interest were identified using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Results: The overall trophoblastic protein expression patterns in preeclamptic and corresponding normotensive placentas were quite similar except for some areas. Of 34 differentially expressed protein spots (p < 0.05 by paired t-test), seven differential proteins from nine spots were identified by MALDI-TOF-MS. The expression of the following proteins was repressed (p < 0.01): disulfide isomerase ER-60, peroxiredoxin 2, and Δ3,5-Δ2,4-dienoyl-CoA isomerase. Four proteins (protein disulfide isomerase precursor, endoplasmic reticulum resident protein, dihydrolipoyl dehydrogenase and TIM21-like protein) were found to be significantly upregulated in PE (p < 0.01). Conclusion: We identified several proteins with significant altered expression in PE using 2D-PAGE. This method is a powerful technique with which to search for not only quantitative but also qualitative changes in a biological process of interest.

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“…Insufficient trophoblast invasion can lead to a number of placental complications such as preeclampsia [26], whereas excessive invasion is associated with disorders such as placenta creta [27]. A finely tuned balance between individual RHO signaling pathways may therefore contribute to the mechanism by which the endometrium controls the appropriate level of trophoblast invasion.…”

Section: Discussionmentioning

confidence: 99%

Human Endometrial Stromal Cell Rho GTPases Have Opposing Roles in Regulating Focal Adhesion Turnover and Embryo Invasion In Vitro1

Grewal

Carver

Ridley

et al. 2010

Biology of Reproduction

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Implantation of the embryo into the uterine compartment is a multistep event involving attachment of the embryo to the endometrial epithelia, followed by invasion of the embryo through the endometrial stroma. RHOA, RAC1, and CDC42 are members of the Rho GTPase family of proteins, which control cell functions such as cell migration and cytoskeletal reorganization. Herein, using a heterologous in vitro coculture model, we show that implantation of mouse blastocysts into human endometrial stromal cells (hESCs) is regulated by Rho GTPase activity in hESCs. Whereas iRNA-mediated silencing of RAC1 expression in hESCs led to inhibition of embryo implantation, silencing of either RHOA or CDC42 in hESCs promoted embryo implantation in coculture assays. Analysis of downstream signaling pathways demonstrated that RAC1 silencing was associated with decreased focal adhesion disassembly and resulted in large focal adhesion complexes in hESCs. In contrast, RHOA or CDC42 silencing resulted in perturbed focal adhesion assembly, leading to a decrease in the number of focal adhesions observed. Furthermore, inhibition of Rho signaling using a Rho kinase inhibitor, Y27632, led to decreased activation of protein tyrosine kinase 2 (PTK2, also called focal adhesion kinase) and decreased focal adhesion assembly. Importantly, perturbation of focal adhesion turnover in hESCs, mediated by PTK2 silencing, resulted in inhibition of embryo implantation into hESC monolayers. These findings suggest that Rho GTPase-PTK2-dependent remodeling of the endometrial stromal cell compartment may be critical for successful embryo implantation.

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Trophoblast Invasion and Placentation: Molecular Mechanisms and Regulation

Cited by 26 publications

References 107 publications

Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

Proteomic Analysis of Proteins Differentially Expressed in Preeclamptic Trophoblasts

Human Endometrial Stromal Cell Rho GTPases Have Opposing Roles in Regulating Focal Adhesion Turnover and Embryo Invasion In Vitro1

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