Integrins β1 and β3 are biomarkers of uterine condition for embryo transfer

Abstract

BackgroundClinical ovulation induction induces blood estrogen (E2) in excess of physiological levels, which can hinder uterine receptivity. In contrast, progesterone produces the opposite clinical effect, suggesting that it might be capable of recovering the lost receptivity resulting from exposure to high estrogen levels. Integrins are the most widely used biological markers for monitoring uterine conditions. We studied progesterone-induced changes in integrin β expression patterns as biomarkers for changes in uterine receptivity in response to increased estrogen levels.MethodsEndometrial biopsy samples from patients were screened for their estrogen (E2) and progesterone (P4) content and expressing levels of integrin β1 and β3. Uterine receptivity was evaluated using human endometrial adenocarcinoma cells in an embryo attachment model. The respective and concatenated effects of embryo attachment and changes in the integrin β1 and β3 expression patterns on the adenocarcinoma cell plasma membranes in response to 100 nM concentrations of E2 and P4 were evaluated.ResultsIncreased blood E2 concentrations were associated with significantly decreased the levels of integrin β3 expression in uterine biopsy samples. In vitro experiments revealed that a 100 nM E2 concentration inhibited the distribution of integrin β3 on the plasma membranes of human endometrial adenocarcinoma cells used in the embryo attachment model, and resulted in decreased rates of embryo attachment. In contrast, P4 enhanced the expression of integrin β1 and promoted its distribution on the plasma membranes. Furthermore, P4 recovered the embryo attachment efficiency that was lost by exposure to 100 nM E2.ConclusionsBlood E2 and P4 levels and integrin β3 and β1 expression levels in uterine biopsy samples should be considered as biomarkers for evaluating uterine receptivity and determining the optimal time for embryo transfer. Trial registration Trial number: ChiCTR-TRC-13003777; Name of registry: Chinese Clinical Trial Registry; Date of registration: 4 September 2013; Date of enrollment of the first study participant: 15 October 2013Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1052-0) contains supplementary material, which is available to authorized users.

Oncostatin M expression in the mouse uterus during early pregnancy promotes embryo implantation and decidualization

“…Because Osm could initiate attachment reaction, we would like to analyze how Osm regulated embryo implantation. However, p-Stat3 and integrin b3 are key mediators for mouse implantation [20,21]. Western blot data showed that both p-Stat3 and integrin b3 (Fig.…”

“…However, p-Stat3 and integrin b3 are key mediators for mouse implantation [20,21]. However, p-Stat3 and integrin b3 are key mediators for mouse implantation [20,21].…”

Receptivity markers in endometrial mesenchymal stem cells of recurrent implantation failure and non‐recurrent implantation failure women: A pilot study

“…17,18,27 ITGβ1 is expressed during the menstrual cycle and probably is involved in reconstruction of uterine epithelium after menstruation. 27 Our assessments revealed that the expression level of ITGb1 in RIF patients MB-derived eMSC was lower than that in the cells isolated from non-RIF patients although the difference was not significant (P > 0.05). No related report on the expression levels of ITGb1 in RIF and infertile patients was found in order to compare the obtained data.…”

Expression of Pinopodes in the Endometrium from Recurrent Pregnancy Loss Women. Role of Thrombomodulin and Ezrin

“…Their function is not well known. They have been associated to molecular markers of endometrial receptivity, like integrins, leukemia inhibiting factor (LIF), l-selectin, glutaredoxin, glycodelin-A, microRNAs and, consistently: (i) their development coincides with the implantation window; (ii) the attachment of a blastocyst occurs at the site of pinopode expression in vitro; (iii) the pinopode surface shows receptors for adhesion molecules that are fundamental for embryo attachment to the uterine mucosa [10][11][12][13]. In conclusion, the ultrastructural organization of endometrial cells and the expression of pinopode represent an important part of the complex process of implantation and are crucial steps for adequate placentation at the beginning of pregnancy.…”