Alternate roles for immune regulators: establishing endometrial receptivity for implantation

Hannan, Natalie J.; Evans, Jemma; Salamonsen, Lois A.

doi:10.1586/eci.11.65

Cited by 29 publications

(18 citation statements)

References 119 publications

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“…Cytokines and chemokines have been shown to play key roles during early implantation events [26]–[30] and their receptors are abundantly expressed by human trophoblast [11]–[13], [31]. Previously we and others have demonstrated that CCL2, 5, and 7 and CX3CL1 are produced by a variety of cell types in the maternal endometrium and have key local actions important for implantation including leukocyte infiltration and trophoblast trafficking [9], [10], [12], [20], [32].…”

Section: Discussionmentioning

confidence: 98%

A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage

et al. 2014

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BackgroundWe have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 (MIC-1) levels are lower in women in early pregnancy who are destined to miscarriage. While promising, the diagnostic performance of measuring MIC-1 alone was not sufficient for it to be a useful predictive test for miscarriage. Besides MIC-1, there are other cytokines, as well as chemokines, involved in facilitating early pregnancy. We reasoned that screening these factors in maternal plasma could uncover other predictive markers of miscarriage.MethodsThis was a nested case control study, of 78 women from a prospective study of 462 attending the Early Pregnancy Assessment Unit in the first trimester (EPAU) with a threatened miscarriage; 34 of these subsequently miscarried (cases) and 44 went on to have a normal delivery (controls) Cytokines IL-1β, IL-6 and IL-10, and the chemokines, CXCL8, CCL2, CCL5, CCL7 and CX3CL1 were measured in plasma from our cohort.ResultsThe cytokines IL-1β, IL-6, IL-10 and the chemokine CXCL8 were not detectable in first trimester plasma. The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in all samples but levels did not vary across 5–12 weeks of gestation among controls. Plasma levels of these chemokines were no different in the miscarriage cohort compared to controls.ConclusionThe chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in plasma during the first trimester while IL-1β, IL-6, IL-10 and CXCL8 were not. However, none of the cytokines and chemokines screened were different in maternal plasma in cases or controls. These therefore do not appear to have potential for application as predictive biomarkers of miscarriage.

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Section: Discussionmentioning

confidence: 98%

A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage

et al. 2014

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“…Details of the specific mechanisms by which known candidates are involved in distinct stages of complex trophoblast-endometrial interactions have been described previously (251). Of the ligands and receptors described in this review, cytokines and chemokines are perhaps the most intriguing signaling ligands in this respect, and more emphasis on these factors is likely to dominate future research (252). Their complementary expression in both the implanting blastocyst and receptive endometrium (LIF, CSFs, etc) ( Figure 2) is highly suggestive of a functional role in the early stages of adhesion, blastocyst anchorage and orientation, and controlled immune suppression to facilitate invasion.…”

Section: Potential Mechanisms Of Implantationmentioning

confidence: 93%

Soluble Ligands and Their Receptors in Human Embryo Development and Implantation

et al. 2015

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Extensive evidence suggests that soluble ligands and their receptors mediate human preimplantation embryo development and implantation. Progress in this complex area has been ongoing since the 1980s, with an ever-increasing list of candidates. This article specifically reviews evidence of soluble ligands and their receptors in the human preimplantation stage embryo and female reproductive tract. The focus will be on candidates produced by the human preimplantation embryo and those eliciting developmental responses in vitro, as well as endometrial factors related to implantation and receptivity. Pathways to clinical translation, including innovative diagnostics and other technologies, are also highlighted, drawing from this collective evidence toward facilitating joint improvements in embryo quality and endometrial receptivity. This strategy could not only benefit clinical outcomes in reproductive medicine but also provide broader insights into the peri-implantation period of human development to improve fetal and neonatal health.

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“…56 Selectins play an important role in leukocyte transendothelial trafficking by mediating leukocyte rolling on the surface of endothelia, 57 and a similar effect of L-selectins on blastocyst apposition to the endometrial epithelium has been suggested. 41,58 As L-selectin is associated with lymphocyte extravasation during inflammation, circulating L-selectin levels may be increased during autoimmune inflammation in patients with type 1 diabetes 59 and Graves disease. 60 L-selectin is also a potential antigenic target because autoantibodies to L-selectin have been described in murine lupus.…”

Section: Adhesion Moleculesmentioning

confidence: 99%

Autoimmune Activation toward Embryo Implantation is Rare in Immune-Privileged Human Endometrium

et al. 2014

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Human embryo implantation represents embryo apposition, adhesion to the endometrial epithelium, and invasion into the stromal extracellular matrix within 1 to 2 days during days 6 to 9 after ovulation. The major molecular mechanisms mediating implantation include adhesion molecules, including mucins, selectins, integrins, and cadherins; extracellular matrix components, such as laminins and collagens and their degrading enzymes; phospholipids and immune regulatory molecules, including prostaglandins, cytokines; and immunosuppressive molecules expressed by invasive trophoblasts and endometrial cells. Many of these molecules are the targets for autoimmune reactions in autoimmune diseases and cancer; however, the relevance of those in immune-mediated implantation failure has not been defined. In this review, we will describe the molecules involved in 2-day event of human embryo implantation, which may also be involved in immune system activation and subsequently cause immune-mediated implantation failure. We speculate that the data in the literature are limited concerning antiendometrial antibodies because the endometrium might be taken as an immune-privileged site that avoids autoimmune activation that might harm the implantation process. Antibodies affecting human fertility in ways other than impairing implantation are outside the scope of the current article and will not be discussed.

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Alternate roles for immune regulators: establishing endometrial receptivity for implantation

Cited by 29 publications

References 119 publications

A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage

A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage

Soluble Ligands and Their Receptors in Human Embryo Development and Implantation

Autoimmune Activation toward Embryo Implantation is Rare in Immune-Privileged Human Endometrium

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