Decidual Control of Trophoblast Invasion

Sharma, Shipra; Godbole, Geeta; Modi, Deepak

doi:10.1111/aji.12466

Cited by 227 publications

(205 citation statements)

References 70 publications

(86 reference statements)

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“…Local concentrations of VEGF in PE can also vary in tissues beyond the placenta. For example, while histologic examination of PE placenta itself may show larger amounts of sFLT-1 and reduced PlGF and VEGF (Yong et al 2015), decidua and decidual immune cells, and perhaps even decidual endothelial cells show higher levels of VEGF release (Sharma et al 2016). So one limitation in dissecting this problem is that studies need to look beyond the placenta and circulation alone and look further at the uterine environment also.…”

Section: Hormones Of Preeclampsia-related Endothelial Dysfunctionmentioning

confidence: 99%

Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Boeldt

Bird

2017

Journal of Endocrinology

249

152

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Maternal vascular adaptation to pregnancy is critically important in order to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones with directly impact endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy but have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell-cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming more clear. We then describe in detail how the complex endocrine environment of PE effects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

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Section: Hormones Of Preeclampsia-related Endothelial Dysfunctionmentioning

confidence: 99%

Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Boeldt

Bird

2017

Journal of Endocrinology

249

152

View full text Add to dashboard Cite

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“…As one of the major roles of decidual cells is the control of trophoblast invasion (Godbole et al 2011, Sharma et al 2016, we next looked at whether adiponectin could modify the ability of decidualized ESCs to regulate this process. Therefore, we used Transwell assays to estimate the trophoblast HTR-8/SVneo cell line invasive capacities when seeded with CM from ESCs treated or not with adiponectin.…”

Section: Discussionmentioning

confidence: 99%

“…This type of ECM remodeling enhances ESC motility and thus facilitates trophoblastic infiltration into the endometrial stroma (Grewal et al 2008). Decidual ECM remodeling is a complex process, tightly controlled by factors intrinsically produced by both placental and decidual cells (Sharma et al 2016). For example, human chorionic gonadotropin (hCG) and tumor necrosis factor alpha (TNF-α) facilitate EVT migration by enhancing endometrial MMP-2,-9 activities and by inhibiting endometrial TIMP-1 secretion (Haider & Knöfler 2009, Tapia-Pizarro et al 2013.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin limits differentiation and trophoblast invasion in human endometrial cells

Duval

Santos

Moindjie

et al. 2017

Journal of Molecular Endocrinology

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Successful human embryo implantation requires a proper differentiation of endometrial stromal cells (ESCs) into decidual cells, during a process called decidualization. ESCs express specific molecules, such as prolactin, insulin-like growth factor-binding protein-1 (IGFBP-1) and connexin-43. Decidual cells are also involved in the control of trophoblast invasion, by secreting various factors, such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Adiponectin is an adipokine with insulin-sensitizing, anti-inflammatory and anti-proliferative effects. At the embryomaternal interface, adiponectin promotes differentiation and invasion of human trophoblastic cells. We hypothesize that the effects of adiponectin on endometrium could counteract its pro-invasive effects previously described in the human trophoblast. In this context, we have firstly demonstrated that adiponectin downregulates IGFBP-1 and connexin-43 mRNA expressions, as well as prolactin secretion in ESCs, suggesting an anti-differentiative effect of adiponectin. Secondly, we found that invasive capacities of trophoblastic cell line HTR-8/SVneo are reduced in the presence of conditioned media from ESC cultured in the presence of adiponectin. Adiponectin's anti-invasive action is associated with a decreased activity of MMP-2 and MMP-9, and an increased TIMP-3 mRNA expression in ESCs. Finally, adiponectin receptors (ADIPOR1 and ADIPOR2) knockdown abolishes the anti-differentiative and anti-invasive effects of adiponectin in human ESCs. Altogether, our results suggest that adiponectin reduces the decidualization process and inversely induces the production of endometrial factors that limit trophoblast invasion. Thus, through a dual control in trophoblast and endometrial cells, adiponectin appears as a pivotal actor of the embryo implantation process.

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“…Migration and invasion of trophoblasts through the decidua and maternal uterine spiral arteries are crucial events in placentation; failure in these processes results in numerous pregnancy complications Sharma et al, 2016). The migration/invasion of trophoblasts is affected by a number of growth factors via the action of small signalling G proteins and phosphorylation of downstream signalling pathways such as MAPK and ERK (Nicola et al, 2008).…”

Section: Chapter 3 -Hcmv Vgpcr Effects Upon Human Cell Types 31 Intrmentioning

confidence: 99%

“…IL-1b, IL-6 and CXCL8 can induce migration and/or invasion of trophoblasts (Sharma et al, 2016). Furthermore, IL-8 expressed by trophoblasts has been reported to stimulate migration of monocytes (Shirasuna et al, 2016).…”

Section: Effects Of Vgpcr In Human Cell Types and Potential Roles Durmentioning

confidence: 99%

Cell-type specific activities of cytomegalovirus GPCR homologues

Oliveira¹

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The human cytomegalovirus (HCMV) is the main agent of congenital infection worldwide. Although primary infections or reactivations do not represent a threat to most individuals, they impose a lifethreating event to a developing foetus or immunocompromised individuals. Although we have learnt much about sites of viral replication and cells involved in the end-stage disease, the specific pathway and essential cell types that the virus must go through to later establish a successful infection and latency is still not clear. HCMV encodes four GPCR homologues (vGPCR): US27, US28, UL33 and UL78. vGPCR have been implicated in viral pathogenesis due to their ability to activate signalling pathways and, thus, alter physiological processes to favour infection. US28 and UL33 have been shown to activate several kinases and transcriptional factors. A key component of both US28 and UL33 sequence is the DRY (Asp/Arg/Tyr) motif, a region directly involved with G protein binding.Because Gα protein content is cell type-dependent, signalling activation by vGPCR can differ from cell to cell. Furthermore, these receptors share the particular characteristic of being constitutively Functional studies demonstrated migration induction of HTR-8 following transfection by either US28 or UL33. In order to investigate potential mechanisms, signalling pathways were probed via detection of activated kinases and the secretion of matrix metalloproteinases (MMP) and chemokines (CK) via luminex assays. Although differences in the level of kinases could not be measured by western blot, induction of MMP and CK were detected by Luminex assays, with contrasting results for US28 and UL33 in transfected cells (HTR-8 and HUVEC). An HCMV recombinant disrupted for US28 signalling (DQY) was generated and compared with wild type HCMV and a US28 null mutant for induction of MMP and CK in virus-infected cells. US28-dependent effects were identified for infected human foreskin fibroblasts, but results for HUVEC were equivocal.iii To determine potential bottlenecks to viral dissemination that may require M33 function(s), mice were infected with M33 knockout (M33) viruses by different routes: intranasal, -mimicking the most natural route, footpad -a more compartmentalized route, and intraperitoneal, the most direct route to major organs. To help track viral dissemination, a luciferase tagged M33 was generated and infection was compared to control virus (M78luc). M33 intranasal infection did not result in attenuation for colonisation of the nose, draining (superficial cervical) lymph nodes (dLN) or the lungs. Via footpad route, M33 colonised the footpad and dLN to levels equivalent to control virus, but was significantly attenuated in spread to the spleen and, subsequently, the salivary glands.Following intraperitoneal infection, the virus is readily delivered to major organs due to direct access to the bloodstream, there was no difference in the colonisation of primary organs (spleen, liver) between M33 and control MCMV, but M33 was still unable ...

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Decidual Control of Trophoblast Invasion

Cited by 227 publications

References 70 publications

Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Adiponectin limits differentiation and trophoblast invasion in human endometrial cells

Cell-type specific activities of cytomegalovirus GPCR homologues

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