Review
Insights into human endometrial receptivity from transcriptomic and proteomic data

https://doi.org/10.1016/j.rbmo.2011.09.009Get rights and content

Abstract

The appreciation of endometrial receptivity is a crucial step in assisted reproductive technology as implantation failures are thought to result, in large part, from abnormal endometrial receptivity. Using emerging omics technologies, investigators have begun to define both molecular signatures and specific biomarkers of receptive endometrium. The aim of this review was to analyse the new perspectives brought to the appreciation of endometrial receptivity by transcriptomic and proteomic technologies, involving the analysis of gene- or protein-expression-profile shifts between the pre-receptive and receptive secretory stages and how they might lead to new strategies for endometrial receptivity assessments. The use of omics as molecular tools to determine the effects of stimulation protocols on endometrial gene expression and clinical outcomes has also been investigated.

The appreciation of endometrial receptivity is a crucial step in assisted reproductive technology as implantation failures are thought to result, in large part, from abnormal endometrial receptivity. Using emerging omics technologies, investigators have begun to define both molecular signatures and specific biomarkers of receptive endometrium. The aim of this review is to analyse the new perspectives brought to the appreciation of endometrial receptivity by omics technologies, involving the analysis of gene- or protein-expression-profile shifts between the pre-receptive and receptive secretory stages, and how they might lead to new strategies for endometrial receptivity assessments. The use of omics during IVF procedures as molecular tools to determine the effects of stimulation protocols on endometrial gene expression and clinical outcomes has also been investigated.

Introduction

Despite the many advances in assisted reproductive technology, lower implantation rates per transferred embryo remain a major problem in IVF. Implantation failure is thought to result, in large part, from abnormal uterine receptivity. Several parameters for assessing endometrial receptivity, such as endometrial morphology and endometrial and subendometrial blood flow, are commonly used in clinical practice, but are unsatisfactory due to their poor predictive value (Aghajanova et al., 2008, Ng et al., 2006, Quinn and Casper, 2009). Omics technologies, such as transcriptomic and proteomic approaches, have recently been used to identify biomarkers of human endometrial receptivity. In this way, some studies have identified new biomarkers of endometrial receptivity by analysing the gene- or protein-expression-profile shift between the pre-receptive and receptive stages of natural cycles (Carson et al., 2002, Domínguez et al., 2009, Díaz-Gimeno et al., 2011, Haouzi et al., 2009a, Li et al., 2006, Mirkin et al., 2005, Riesewijk et al., 2003, Talbi et al., 2006). A transcriptomic approach has been used to identify the impact of the different ovarian stimulation protocols used in IVF treatment on endometrial receptivity, by comparing either the receptive gene-expression profile between natural and stimulated cycles in different groups of patients (Horcajadas et al., 2005, Horcajadas et al., 2008, Liu et al., 2008, Mirkin et al., 2004, Simon et al., 2005) or the gene-expression-profile shift during the pre-receptive and receptive stages of natural versus stimulated cycles in the same patients (Haouzi et al., 2009b, Haouzi et al., 2010).

The aim of this review was to analyse the new insights on endometrial receptivity brought about by omics technologies, namely: (i) gene, protein or molecular signature used as biomarkers of endometrial receptivity and their predictive value in forecasting pregnancy outcome during IVF treatments; and (ii) transcriptomic profiling to determine the impact of ovarian stimulation protocols during IVF cycles.

Section snippets

Natural cycles

Recently, transcriptomic approaches have been used to identify biomarkers of the implantation window. Several studies have reported modifications in gene-expression profiles associated with the transition of the human endometrium from a pre-receptive (LH + 1/5) to a receptive (LH + 7/9) stage (Carson et al., 2002, Díaz-Gimeno et al., 2011, Haouzi et al., 2009a, Mirkin et al., 2005, Riesewijk et al., 2003, Talbi et al., 2006). However, only two genes were common to all these studies (Figure 1, Table

Endometrial biopsies

Previously, very few investigators have applied large-scale proteomic techniques to study endometrial receptivity. Of these reports, one focused on comparison between proliferative and secretory-phase endometrium using isotope-coded affinity-tag technology (DeSouza et al., 2005), whereas two others used two-dimensional differential in-gel electrophoresis (2D DIGE) followed by matrix-assisted laser desorption/ionization tandem time-of-flight MS to compare either late-proliferative and

Conclusions and perspectives

The use of omics tools to explore endometrial receptivity under stimulated cycles for IVF/ICSI contributes to improving the implantation and pregnancy success rate. Gene- as well as protein-expression profiles of endometrial receptivity under natural and stimulated cycles reveal significant differences. To date, transcriptomic and proteomic data have provided a set of genes or proteins that can be used as biomarkers for the assessment of the receptive status of the human endometrium. In

Acknowledgements

The authors thank the University-Hospital of Montpellier, the Association Française contre les Myopathies (AFM), Vitrolife, Genevrier, CCD and Ferring Pharmaceutical Companies for their support.

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    Delphine Haouzi obtained her PhD from the University of Paris 7. Since 2007, she has been working on human endometrial receptivity and embryonic implantation. Her investigations have focused on the identification of biomarkers of human endometrial receptivity using microarray technology. She also investigated the impact of ovarian stimulation on endometrial receptivity as well as the understanding of early dialogues between trophectoderm and endometrial cells during the implantation period.

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