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.
Highlights
Clinical ovulation induction induces blood estrogen (E2) in excess of physiological levels, which can hinder uterine receptivity
Up-regulation of integrin β3 by the blastocyst has been proved in co-cultured human endometrial epithelial cells, which might be mediated by the embryonic IL-1 system [14]
Inhibition of integrin β1 and β3 expression was associated with increased E2 level It is known that integrin is one major member of extracellular matrix protein to modulate cell migration, cell– cell junction and embryo implantation
Summary
Clinical ovulation induction induces blood estrogen (E2) in excess of physiological levels, which can hinder uterine receptivity. We studied progesterone-induced changes in integrin β expression patterns as biomarkers for changes in uterine receptivity in response to increased estrogen levels. Assisted reproduction techniques such as ovulation induction, in vitro fertilization (IVF), and embryo transfer (ET) have enabled patients to overcome a variety of human infertility disorders. The specific participation of integrins in implantation has early been demonstrated: based on the previous studies, members of integrins play key roles in the signaling [9], maintenance of epithelial polarity [10], and developmental progression of placental cytotrophoblast to an invasive phenotype [11]. Integrins are some of the best characterized biomarkers of uterine receptivity, and the roles they play in implantation have been widely reviewed [15,16,17]
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