Mouse double minute homologue 2 (MDM2) downregulation by miR-661 impairs human endometrial epithelial cell adhesive capacity

Winship, Amy; Ton, Amanda; Sinderen, Michelle Van; Menkhorst, Ellen; Rainczuk, Katarzyna; Griffiths, Meaghan; Cuman, Carly; Dimitriadis, Evdokia

doi:10.1071/rd17095

Cited by 19 publications

(21 citation statements)

References 37 publications

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“…The xCELLigence technology which incorporates real-time monitoring of cell adhesion is also used as an approach to determine endometrial cell adhesive capacity (46). In this assay, endometrial epithelial cells adhesion is measured either directly on attachment to plastic plates or the plates are coated with various extracellular matrix (ECM) proteins and endometrial epithelial cell adhesion measured via electrical impedance in realtime (75). The TER assay is used to measure the integrity of interepithelial cell-tight junctions in vitro (44).…”

Section: In Vitro Assays Used To Investigate Plasma Membrane Transformentioning

confidence: 99%

Alterations in Epithelial Cell Polarity During Endometrial Receptivity: A Systematic Review

2020

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Background: Abnormal endometrial receptivity is one of the major causes of embryo implantation failure and infertility. The plasma membrane transformation (PMT) describes the collective morphological and molecular alterations occurring to the endometrial luminal epithelium across the mid-secretory phase of the menstrual cycle to facilitate implantation. Dysregulation of this process directly affects endometrial receptivity and implantation. Multiple parallels between these alterations to confer endometrial receptivity in women have been drawn to those seen during the epithelial-mesenchymal transition (EMT) in tumorigenesis. Understanding these similarities and differences will improve our knowledge of implantation biology, and may provide novel therapeutic targets to manage implantation failure. Methods: A systematic review was performed using the Medline (Ovid), Embase, and Web of Science databases without additional limits. The search terms used were "(plasma membrane* or cell membrane*) and transformation*" and "endometrium or endometrial." Research studies on the PMT or its regulation in women, discussing either the endometrial epithelium, decidualized stroma, or both, were eligible for inclusion. Results: A total of 198 articles were identified. Data were extracted from 15 studies that matched the inclusion criteria. Collectively, these included studies confirmed the alterations occurring to the endometrial luminal epithelium during the PMT are similar to those seen during the EMT. Such similarities included alterations to the actin cytoskeleton remodeling of adherens junctions, integrin expression and epithelial-stromal communication. These were also some differences between these processes, such as the regulation of tight junctions and mucins, which need to be further researched. Conclusions: This review raised the prospect of shared and distinct mechanisms existing in PMT and EMT. Further investigation into similarities between the PMT in the endometrium and the EMT in tumorigenesis may provide new mechanistic insights into PMT and new targets for the management of implantation failure and infertility.

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Section: In Vitro Assays Used To Investigate Plasma Membrane Transformentioning

confidence: 99%

Alterations in Epithelial Cell Polarity During Endometrial Receptivity: A Systematic Review

2020

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“…A panel of miRs will likely to be included, with the functional consequence of each individual miR on implantation being confirmed in ideally both humans ( in vitro ) and preclinical animal models ( in vivo ). Detailed functional studies have only covered a small proportion of miRs identified so far ( Table 2 ; Chu et al, 2015 ; Cuman et al, 2015 ; Kang et al, 2015 ; Kottawatta et al, 2015 ; Vilella et al, 2015 ; Zhang et al, 2015 ; Cai et al, 2016 ; Chen et al, 2016 ; Zheng et al, 2017 ; Sirohi et al, 2018 ; Winship et al, 2018 ; Balaguer et al, 2019 ; Griffiths et al, 2019 ; Takamura et al, 2019 ).…”

Section: Spent Blastocyst Culture Mediummentioning

confidence: 99%

Secreted MicroRNA to Predict Embryo Implantation Outcome: From Research to Clinical Diagnostic Application

Zhou

Dimitriadis

2020

Front. Cell Dev. Biol.

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Embryo implantation failure is considered a leading cause of infertility and a significant bottleneck for in vitro fertilization (IVF) treatment. Confirmed factors that lead to implantation failure involve unhealthy embryos, unreceptive endometrium, and asynchronous development and communication between the two. The quality of embryos is further dependent on sperm parameters, oocyte quality, and early embryo development after fertilization. The extensive involvement of such different factors contributes to the variability of implantation potential across different menstrual cycles. An ideal approach to predict the implantation outcome should not compromise embryo implantation. The use of clinical material, including follicular fluid, cumulus cells, sperm, seminal exosomes, spent blastocyst culture medium, blood, and uterine fluid, that can be collected relatively non-invasively without compromising embryo implantation in a transfer cycle opens new perspectives for the diagnosis of embryo implantation potential. Compositional comparison of these samples between fertile women and women or couples with implantation failure has identified both quantitative and qualitative differences in the expression of microRNAs (miRs) that hold diagnostic potential for implantation failure. Here, we review current findings of secreted miRs that have been identified to potentially be useful in predicting implantation outcome using material that can be collected relatively non-invasively. Developing non-invasive biomarkers of implantation potential would have a major impact on implantation failure and infertility.

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“…There are many known regulators of human receptivity, including leukemia inhibitory factor (LIF) and interleukin 11 (IL-11) 7–10 , and more recently microRNA (miR) have been implicated to regulate endometrial receptivity and blastocyst implantation 11 . miR have been identified to be expressed and secreted by both human endometrium and blastocysts and consequently taken up by the opposite to have downstream effects on gene targets 12–14 .…”

Section: Introductionmentioning

confidence: 99%

miR-29c overexpression and COL4A1 downregulation in infertile human endometrium reduces endometrial epithelial cell adhesive capacity in vitro implying roles in receptivity

Griffiths

Sinderen

Rainczuk

et al. 2019

Sci Rep

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The endometrium is a highly complex tissue that is vulnerable to subtle gene expression changes and is the first point of contact for an implanting blastocyst. Successful blastocyst implantation can only occur when the endometrium is receptive during a short window with each menstrual cycle. microRNAs are small, non-coding RNAs that negatively regulate their gene targets. miR-29c has previously been identified to be differentially regulated across the fertile menstrual cycle, however it has not been investigated in association with infertility. We hypothesised that miR-29c dysregulation in the infertile endometrium would negatively influence endometrial adhesion and blastocyst implantation outcomes during the mid-secretory, receptive phase. miR-29c expression was elevated in early and mid-secretory phase infertile endometrium and localised to the epithelial compartments of endometrial tissue. Overexpression of miR-29c in vitro impaired endometrial epithelial adhesion, and reduced collagen type IV alpha 1 (COL4A1) mRNA expression. COL4A1 was immunolocalised to the luminal and glandular epithelial basement membranes in early and mid-secretory phase fertile and infertile endometrium for the first time. Knockdown of COL4A1 impaired endometrial epithelial adhesion suggesting a role in endometrial receptivity and implantation. Our data suggests miR-29c overexpression with infertility may impair the adhesive capacity of the endometrium, potentially contributing to implantation failure and infertility.

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Mouse double minute homologue 2 (MDM2) downregulation by miR-661 impairs human endometrial epithelial cell adhesive capacity

Cited by 19 publications

References 37 publications

Alterations in Epithelial Cell Polarity During Endometrial Receptivity: A Systematic Review

Alterations in Epithelial Cell Polarity During Endometrial Receptivity: A Systematic Review

Secreted MicroRNA to Predict Embryo Implantation Outcome: From Research to Clinical Diagnostic Application

miR-29c overexpression and COL4A1 downregulation in infertile human endometrium reduces endometrial epithelial cell adhesive capacity in vitro implying roles in receptivity

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