Abstract

BackgroundSelection of the best oocyte for subsequent steps of fertilization and embryo transfer was shown to be the crucial step in human infertility treatment procedure. Oocyte selection using morphological criteria mainly Zona pellucida (ZP) has been the gold standard method in assisted reproductive technologies (ART) clinics, but this selection approach has limitations in terms of accuracy, objectivity and constancy. Recent studies using OMICs-based approaches have allowed the identification of key molecular markers that quantitatively and non-invasively predict the oocyte quality for higher pregnancy rates and efficient infertility treatment. These biomarkers are a valuable reinforcement of the morphological selection criteria widely used in in vitro fertilization (IVF) clinics. In this context, this study was designed to investigate the relationship between transcriptomic predictors of oocyte quality found by our group and the conventional morphological parameters of oocyte quality mainly the ZP birefringence.ResultsMicroarray data revealed that 48 and 27 differentially expressed candidate genes in cumulus cells (CCs) were respectively overexpressed and underexpressed in the ZGP (Zona Good Pregnant) versus ZBNP (Zona Bad Non Pregnant) groups. More than 70% of previously reported transcriptomic biomarkers of oocyte developmental competence were confirmed in this study. The analysis of possible association between ZP birefringence versus molecular markers approach showed an absence of correlation between them using the current set of markers.ConclusionsThis study suggested a new integrative approach that matches morphological and molecular approaches used to select developmentally competent oocytes able to lead to successful pregnancy and the delivery of healthy baby. For each ZP birefringence score, oocytes displayed a particular CCs' gene expression pattern. However, no correlations were found between the 7 gene biomarkers of oocyte developmental potential and the ZP birefringence score. Further studies using larger lists of candidate markers are required to identify suitable genes that are highly correlated with the morphological criteria, and therefore able to reinforce the accuracy of oocyte selection and the effectiveness of infertility treatment.

Highlights

  • Selection of the best oocyte for subsequent steps of fertilization and embryo transfer was shown to be the crucial step in human infertility treatment procedure

  • The cumulus-oocyte complex (COC) morphology and cytology are amongst the main parameters that have been used in assisted reproductive technologies (ART) clinics to select the best oocyte for subsequent steps of fertilization and early embryo development in human and livestock species [6,7]

  • Gene expression analysis RNA hybridizations were performed on a custom-made microarray platform enriched in cumulus cells (CCs), granulosa cells (GCs), oocytes and early embryos ESTs using suppressive subtractive hybridization (SSH) of cDNA sequences as described elsewhere [56,57]

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Summary

Introduction

Selection of the best oocyte for subsequent steps of fertilization and embryo transfer was shown to be the crucial step in human infertility treatment procedure. Recent studies using OMICsbased approaches have allowed the identification of key molecular markers that quantitatively and non-invasively predict the oocyte quality for higher pregnancy rates and efficient infertility treatment These biomarkers are a valuable reinforcement of the morphological selection criteria widely used in in vitro fertilization (IVF) clinics. Numerous studies focused on the criteria allowing an efficient selection of high-quality oocytes, named competent oocytes, for assisted reproduction procedure using both human and animal models Such oocyte competence is defined as its ability to properly achieve full maturation at nuclear, cytoplasmic and molecular levels, to achieve successful steps of fertilization and early embryo development, and to lead to a viable and healthy offspring [3,4,5]. CCs were shown to enhance the oocyte quality by their physical presence (cell-cell adhesion structures), their morphology [12,13], their metabolic and signal transduction functions [14,15,16,17]

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