Decidual-Secreted Factors Alter Invasive Trophoblast Membrane and Secreted Proteins Implying a Role for Decidual Cell Regulation of Placentation

Menkhorst, Ellen; Lane, Natalie; Winship, Amy; Li, Priscilla; Yap, Joanne; Meehan, Katie; Rainczuk, Adam; Stephens, Andrew N.

doi:10.1371/journal.pone.0031418

Cited by 42 publications

(34 citation statements)

References 84 publications

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“…Decidualization in vitro predominantly activates ligands of receptors in the adjacent trophoblast cells. This is consistent with the observations that the presence of factors from the maternal decidua affects the growth of trophoblast cells (Menkhorst et al 2012). The potential to receive incoming trophoblast signals is similar between endometrial stromal fibroblasts and in vitro decidualized cells.…”

Section: Empirical Validationsupporting

confidence: 91%

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface

et al. 2017

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Organismal function is, to a great extent, determined by interactions among their fundamental building blocks, the cells. In this work, we studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics. The placental interface mediates the interaction between two semiallogenic individuals, the mother and the fetus, and is thus the epitome of cell interactions. To study these, we inferred the cell-cell interactome by assessing the gene expression of receptor-ligand pairs across cell types. We find a highly cell-type-specific expression of G-protein-coupled receptors, implying that ligand-receptor profiles could be a reliable tool for cell type identification. Furthermore, we find that uterine decidual cells represent a cell-cell interaction hub with a large number of potential incoming and outgoing signals. Decidual cells differentiate from their precursors, the endometrial stromal fibroblasts, during uterine preparation for pregnancy. We show that decidualization (even in vitro) enhances the ability to communicate with the fetus, as most of the receptors and ligands up-regulated during decidualization have their counterpart expressed in trophoblast cells. Among the signals transmitted, growth factors and immune signals dominate, and suggest a delicate balance of enhancing and suppressive signals. Finally, this study provides a rich resource of gene expression profiles of term intravillous and extravillous trophoblasts, including the transcriptome of the multinucleated syncytiotrophoblast.

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Section: Empirical Validationsupporting

confidence: 91%

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface

et al. 2017

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“…Although the effects are cell line dependent, DCM increases the expression of MMP‐2, ‐3 and ‐9, and inhibits the expression of TIMP‐1,‐2 and ‐3 in ACH3P cells; in JEG‐3 cells, DCM increased the expression of TIMP‐2 and repressed TIMP‐1 and TIMP‐3 . In addition, an increased secretion of other proteases has also been observed in response to DCM . Such altered ratio of MMPs and TIMPs along with activation of other proteases would allow degradation of the extracellular matrix, thereby facilitating invasion.…”

Section: Decidual Cells Promote Trophoblast Invasionmentioning

confidence: 76%

“…This effect is specific to decidualized cells, as primary stromal cells or pre‐decidual cells did not have any major effects on number invading trophoblasts across matrigel . A stimulatory effect of DCM on invasion of primary EVTs has also been reported . These observations imply that secretions from the decidualized stromal cells have pro‐invasive properties.…”

Section: Decidual Cells Promote Trophoblast Invasionmentioning

confidence: 99%

“…We observed that DCM increased the expression of both α5 and α6 subunits in the trophoblast cells, without affecting the expression of β3 . Beyond these, several proteins including those involved in cell–cell adhesion and matrix remodelling are also secreted by the trophoblast cells in response to DCM . Thus, decidualization‐driven changes in the uterine cells seem to create a microenvironment favourable for implantation and placentation.…”

Section: Decidual Cells Promote Trophoblast Invasionmentioning

confidence: 99%

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Decidual Control of Trophoblast Invasion

Sharma

Godbole

Modi

2016

American J Rep Immunol

223

184

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At the time of implantation, the trophoblast cells of the embryo adhere and then invade into the maternal endometrium and eventually establish placentation. The endometrium at the same time undergoes decidualization, which is essential for successful pregnancy. While the NK cells of the decidua have been implicated to play a key role in trophoblast invasion, few evidence are now available to demonstrate a pro-invasive property of decidual stromal cells. Secretions from decidualized endometrial stromal cells promote invasion of primary trophoblasts and model cell lines by activating proteases and altering expression of adhesion-related molecules. The decidual secretions contain high amounts of pro-invasive factors that include IL-1b, IL-5, IL-6, IL-7, IL-8, IL-9, IL-13, IL-15, Eotaxin CCL11, IP-10 and RANTES, and anti-invasive factors IL-10, IL-12 and VEGF. It appears that these decidual factors promote invasion by regulating the protease pathways and integrin expression utilizing the STAT pathways in the trophoblast cells. At the same time the decidua also seem to secrete some anti-invasive factors that are antagonist to the matrix metalloproteinases and/or are activators of tissue inhibitors of metalloproteinases. This might be essential to neutralize the effects of the invasionpromoting factors and restrain overinvasion. It is tempting to propose that during the course of pregnancy, the decidua must balance the production of these pro and anti-invasive molecules and such harmonizing production would allow a timely and regulated invasion.

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“…cells, becoming rounded with altered expression and secretion of extracellular matrix (ECM) (Menkhorst et al, 2012).…”

mentioning

confidence: 99%

Dipeptidyl peptidase IV reduces trophoblast invasion by inhibiting the activity of MMPs

Li¹,

Li²,

Zhang³

2014

Int. J. Dev. Biol.

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Preeclampsia is a severe pregnancy complication in part due to insufficient implantation. This study aimed at elucidating the mechanism of action of dipeptidyl peptidase IV (DPPIV) in preeclampsia. Small activating RNAs (saRNA) were used to upregulate DPPIV expression in human trophoblast JAR cells. The DPPIV expression level was analyzed by real-time quantitative PCR and western blot and its activity was measured by luminescent protease assay. MMP-9 activity was analyzed by zymography and cell invasion by matrigel invasion assay. DPPIV expression level and activity was significantly increased by saRNA in JAR cells. DDPIV specific inhibitor diprotin A inhibited its activity at both basal and activated levels. DPPIV did not regulate MMP-9 expression but did repress MMP-9 activity. The invading ability of JAR cells was reduced by saRNA but increased by diprotin A. DPPIV might be responsible for the shallow implantation of the placenta due to its inhibition of the invading ability of extravillous trophoblasts, causing preeclampsia at later stage of pregnancy. KEY WORDS: preeclampsia, trophoblast, dipeptidyl peptidase IV, small activating RNA, cell invasion, diprotin APreeclampsia is a severe complication which affects 5-8% of pregnancies and contributes significantly to maternal and fetal morbidity and mortality (Steegers et al., 2010). Moreover, women with preeclampsia have an increased risk of developing cardiovascular disease later in life. Preeclampsia is thought to be resulted from a complex interplay between genetic and environmental factors. Family studies provides the evidence for the involvement of genetic factors, which have shown that daughters and sisters of preeclamptic women have a higher risk of preeclampsia (Nilsson et al., 2004). Moreover, the incidence of preeclampsia is also different among various ethnic groups (Steegers et al., 2010). Unfortunately, the precise etiology of preeclampsia remains unclear after decades of efforts.It is required for a blastocyst to implant into the uterine endometrium to form a functional placenta during the establishment of mammalian pregnancy. A functional placenta formation requires the 'extravillous trophoblast' (EVT) engrafting and remodeling uterine spiral arteries to create placental blood supply at the end of the first trimester (Burton et al., 2010). Shallow or inappropriate implantation and placentation may result in first trimester miscarriage, preeclampsia, and other obstetric complications (Aplin, 2010). The trophoblast invasion is regulated by local endometrial environment that endometrial stromal cells differentiate into decidual Int.

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Decidual-Secreted Factors Alter Invasive Trophoblast Membrane and Secreted Proteins Implying a Role for Decidual Cell Regulation of Placentation

Cited by 42 publications

References 84 publications

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface

Decidual Control of Trophoblast Invasion

Dipeptidyl peptidase IV reduces trophoblast invasion by inhibiting the activity of MMPs

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