The long noncoding RNA PTENP1 regulates human endometrial epithelial adhesive capacity in vitro: implications in infertility

Takamura, Masashi; Zhou, Wei; Rombauts, Luk; Dimitriadis, Evdokia

doi:10.1093/biolre/ioz173

Cited by 19 publications

(24 citation statements)

References 36 publications

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“…A previous study confirms the upregulation of miR-223-3p in human endometrium with a compromised receptivity phenotype and its interaction with LIF [49]. In support, in our recent study we reveal that miR-223-3p is detected at low levels in the primary fertile human endometrial epithelial cells [50]. However, whether CDH6 is directly regulated by miR-223-3p in the infertile human endometrium is unknown.…”

Section: Discussionsupporting

confidence: 88%

Characterization of the role for cadherin 6 in the regulation of human endometrial receptivity

Zhou

Santos

Dimitriadis

2020

Reprod Biol Endocrinol

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Background: The endometrial luminal epithelium is the first point of attachment of embryos during implantation. Failure of embryos to firmly adhere results in implantation failure and infertility. A receptive endometrial luminal epithelium is achieved through the expression of adhesion molecules in the mid-secretory phase and is a requirement for implantation. Cadherin 6 (CDH6) is an adhesion molecule localizing to the endometrial luminal epithelial cell surface in the mid-secretory/receptive phase and knockdown of CDH6 in the Ishikawa cells (receptive endometrial epithelial cell line) compromises cell integrity. However, there are no studies investigating the role of CDH6 on receptivity and infertility. This study aimed to investigate whether CDH6 is dysregulated in the endometrium of women with infertility during the receptive window and the effect of CDH6 on endometrial adhesion and receptivity. Methods: The expression and the localization of CDH6 in the human endometrium were determined by immunohistochemistry. Ishikawa cells were used to investigate the functional consequences of CDH6 knockdown on endometrial adhesive capacity to HTR8/SVneo (trophoblast cell line) spheroids in vitro. CDH6 knockdown was assessed by qPCR and immunoblotting. After CDH6 knockdown, the expression of type II cadherin family members and CDH6 functional partners were assessed by qPCR. Two-tailed unpaired student's t-test or one-way ANOVA as appropriate were used for statistical analysis with a significance threshold of P < 0.05. Results: A significant reduction of CDH6 immunolocalization was recorded in the luminal and glandular epithelium of endometrium from women with infertility (P < 0.05) compared to fertile group respective cellular compartments in the mid-secretory phase. Functional analysis using Ishikawa cells demonstrated that knockdown of CDH6 (treated with 50 nM CDH6 siRNA) significantly reduced epithelial adhesive capacity (P < 0.05) to HTR8/SVneo spheroids compared to control and other type II cadherin family members likely failed to compensate for the loss of CDH6. The expression levels of CDH6 functional partners, catenin family members were not changed after CDH6 knockdown in Ishikawa cells.

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Section: Discussionsupporting

confidence: 88%

Characterization of the role for cadherin 6 in the regulation of human endometrial receptivity

Zhou

Santos

Dimitriadis

2020

Reprod Biol Endocrinol

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“…A recent study also demonstrates that incubation of HEECs with BCM from embryos that implanted, compared to embryos that did not implant during IVF, leads to a substantial change in the expression of long non-coding RNAs in the HEECs (Takamura et al, 2019). PTENP1 is one of the most decreased long non-coding RNAs in HEECs after being treated with BCM from embryos that fail to implant (Takamura et al, 2019). Functionally, knockdown of PTENP1 impairs HEEC adhesion via a miR-dependent mechanism to downregulate gene targets essential for receptivity (Takamura et al, 2019).…”

Section: Spent Blastocyst Culture Mediummentioning

confidence: 96%

“…PTENP1 is one of the most decreased long non-coding RNAs in HEECs after being treated with BCM from embryos that fail to implant (Takamura et al, 2019). Functionally, knockdown of PTENP1 impairs HEEC adhesion via a miR-dependent mechanism to downregulate gene targets essential for receptivity (Takamura et al, 2019). The implanted and non-implanted embryos from which BCM was collected had an indistinguishable morphology based on currently available assessment of embryo quality.…”

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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“…This assay generally involves both endometrial epithelial cells and trophoblast cell spheroids to mimic the blastocyst attachment. The assay uses mechanical force to determine the adhesive capacity of endometrial epithelial cells (73). In some studies, spheroids are replaced with mouse embryos and in very rare cases human IVF blastocysts are co-cultured with a primary human endometrial epithelial/stromal cell bilayer (74).…”

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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The long noncoding RNA PTENP1 regulates human endometrial epithelial adhesive capacity in vitro: implications in infertility

Cited by 19 publications

References 36 publications

Characterization of the role for cadherin 6 in the regulation of human endometrial receptivity

Characterization of the role for cadherin 6 in the regulation of human endometrial receptivity

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

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

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