Said Assou

Université de Montpellier 1, Montpelhièr, Languedoc-Roussillon, France

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Publications (70)178.76 Total impact

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    ABSTRACT: To evaluate the effect of induced blastocoele shrinkage before vitrification in a closed carrier device. Prior to vitrification, blastocyst cavity was artificially shrinked by laser pulse or not treated according to a 2:1 randomized procedure. A total of 185 warming cycles from April 2011 to March 2013 have been analyzed. Clinical pregnancy rate and survival rate were compared between the two groups. The mean (±SD) women age was 33.5±5.7 years for both groups. The pregnancy rate in the group with artificial reduction of the cavity was higher ([32/67] 47.7%) than in the control group but not significantly ([43/113] 38%). The survival rate in the artificial shrinkage group was significantly higher compared with the control group : 99% (102/103) and 91.8% (168/183) respectively (P=0.01). This study reveals that artificial shrinkage of blastocoelic cavity by laser pulse before vitrification in a closed carrier device improves survival rate after warming. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    Gynécologie Obstétrique & Fertilité 11/2014; 42(11):772-8. · 0.55 Impact Factor
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    ABSTRACT: Proper folliculogenesis is fundamental to obtain a competent oocyte that, once fertilized, can support the acquisition of embryo developmental competence and pregnancy. MicroRNAs (miRNAs) are crucial regulators of folliculogenesis, which are expressed in the cumulus-oocyte complex and in granulosa cells and some can also be found in the bloodstream. These circulating miRNAs are intensively studied and used as diagnostic/prognostic markers of many diseases, including gynecological and pregnancy disorders. In addition, serum contains small amounts of cell-free DNA (cfDNA), presumably resulting from the release of genetic material from apoptotic/necrotic cells. The quantification of nucleic acids in serum samples could be used as a diagnostic tool for female infertility.
    Human Reproduction Update 06/2014; · 8.85 Impact Factor
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    ABSTRACT: The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL) on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity.
    BioMed Research International 01/2014; 2014:951937. · 2.71 Impact Factor
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    ABSTRACT: Pre-implantation genetic diagnosis (PGD) is a powerful clinical tool to identify embryos with or at risk of specific genetic diseases before implantation in utero after in vitro fertilization (IVF). PGD is performed on embryo biopsies that are obtained by aspiration of one or two cells from pre-implantation embryos at day 3 or day 5/6 of culture. However this is a traumatic method that cannot be avoided because non-invasive procedures to assess the genetic status of pre-implantation embryos are not available yet. We hypothesize that cell-free nucleic acids, which are released by embryos in the culture medium during the IVF procedure, could be used for genetic screening. To test our hypothesis we will focus first on X-linked disorders because these single-gene diseases due to the presence of defective genes on the X chromosome are dominant in males. Therefore the objective here is to discriminate between female (XX) and male (XY) embryos by detecting Y chromosome-specific sequences in cell-free nucleic acids. Using culture medium from embryos we are able to discriminate between male and female embryos. This opens new avenues for the development of a non-invasive PGD method.
    Medical Hypotheses. 01/2014;
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    ABSTRACT: Impact of female aging is an important issue in human reproduction. There was a need for an extensive analysis of age impact on transcriptome profile of cumulus cells (CCs) to link oocyte quality and developmental potential with patient's age. CCs from patients of three age groups were analyzed individually using microarrays. RT-qPCR validation was performed on independent CC cohorts. We focused here on pathways affected by aging in CCs that may explain the decline of oocyte quality with age. In CCs collected from patients >37 years, angiogenic genes including ANGPTL4, LEPR, TGFBR3, and FGF2 were significantly overexpressed compared to patients of the two younger groups. In contrast genes implicated in TGF-β signaling pathway such as AMH, TGFB1, inhibin, and activin receptor were underexpressed. CCs from patients whose ages are between 31 and 36 years showed an overexpression of genes related to insulin signaling pathway such as IGFBP3, PIK3R1, and IGFBP5. A bioinformatic analysis was performed to identify the microRNAs that are potential regulators of the differentially expressed genes of the study. It revealed that the pathways impacted by age were potential targets of specific miRNAs previously identified in our CCs small RNAs sequencing.
    BioMed Research International 01/2014; 2014:964614. · 2.71 Impact Factor
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    ABSTRACT: Apoptotic cell death has been reported in human oocytes and preimplantation embryos under in vivo and in vitro conditions. BCL-2 family proteins comprise both anti- and pro-apoptotic members, which are likely to play a key role in controlling oocyte and early embryo survival. However, very limited data are available on their expression kinetics during human early embryonic development. Using our DNA microarray data, we analyzed the expression pattern of 21 BCL-2 family genes in human mature MII oocytes, day 3 embryos and day 5/6 blastocysts from patients who underwent in vitro fertilization (IVF). Selected genes were further validated by qRT-PCR and their subcellular localization analyzed by immunofluorescence confocal microscopy. Our results suggest a switch from oocyte-inherited BCL-2 family transcripts, such as BCL2L10, to embryo-produced transcripts after embryonic genome activation, including BIK, BCL2L11 and NOXA. Moreover, the pro-apoptotic gene BCL2L13 was constitutively expressed throughout human early embryonic development. Remarkably, day 3 embryos expressed more BCL-2 pro-apoptotic genes than mature MII oocytes and day 5/6 blastocysts, suggesting that embryos at this stage are more prone to apoptosis. This is further supported by an absence of cleaved Caspase-3 in the oocyte and its presence in the embryo. Using a drug that induces apoptosis (gambogic acid), we were able to show activated Caspase-3 in the oocyte in addition to an alteration of BCL2L13 protein localization. Similarly BCL2L13 localization was altered in degenerated oocytes. This study opens new perspectives for understanding the molecular regulation of human oocyte and pre-implantation embryo survival and death.
    Current Medicinal Chemistry 09/2013; · 3.72 Impact Factor
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    ABSTRACT: What is the expression pattern of microRNAs (miRNAs) in human cumulus-oocyte complexes (COCs)? Several miRNAs are enriched in cumulus cells (CCs) or oocytes, and are predicted to target genes involved in biological functions of the COC. The transcriptional profiles of human MII oocytes and the surrounding CCs are known. However, very limited data are available about post-transcriptional regulators, such as miRNAs. This is the first study focussing on the identification and quantification of small RNAs, including miRNAs, in human oocytes and CCs using a deep-sequencing approach. MII oocytes and CCs were collected from women who underwent IVF. Using the Illumina/deep-sequencing technology, we analyzed the small RNAome of pooled MII oocytes (n = 24) and CC samples (n = 20). The mRNA targets of CC and MII oocyte miRNAs were identified using in silico prediction algorithms. Using oligonucleotide microarrays, genome-wide gene expression was studied in oocytes (10 pools of 19 ± 3 oocytes/each) and 10 individual CC samples. TaqMan miRNA assays were used to confirm the sequencing results in independent pools of MII oocytes (3 pools of 8 ± 3 oocytes/each) and CC samples (3 pools of 7 ± 3 CCs/each). The functional role of one miRNA, MIR23a, was assessed in primary cultures of human CCs. Deep sequencing of small RNAs yielded more than 1 million raw reads. By mapping reads with a single location to the human genome, known miRNAs that were abundant in MII oocytes (MIR184, MIR100 and MIR10A) or CCs (MIR29a, MIR30d, MIR21, MIR93, MIR320a, MIR125a and the LET7 family) were identified. Predicted target genes of the oocyte miRNAs were associated with the regulation of transcription and cell cycle, whereas genes targeted by CC miRNAs were involved in extracellular matrix and apoptosis. Comparison of the predicted miRNA target genes and mRNA microarray data resulted in a list of 224 target genes that were differentially expressed in MII oocytes and CCs, including PTGS2, CTGF and BMPR1B that are important for cumulus-oocyte communication. Functional analysis using primary CC cultures revealed that BCL2 and CYP19A1 mRNA levels were decreased upon MIR23a overexpression. Only known miRNAs were investigated in the present study on COCs. Moreover, the source of the material is MII oocytes that failed to fertilize. The present findings suggest that miRNA could play a role in the regulation of the oocyte and CC crosstalk. This work was partially supported by a grant from Ferring Pharmaceuticals. The authors of the study have no conflict of interest to report. Not applicable.
    Human Reproduction 07/2013; · 4.67 Impact Factor
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    ABSTRACT: In in vitro fertilization cycles, both HP-hMG and rFSH gonadotropin treatments are widely used to control human follicle development. The objectives of this study are (i) to characterize and compare gene expression profiles in cumulus cells (CCs) of periovulatory follicles obtained from patients stimulated with HP-hMG or rFSH in a GnRH antagonist cycle and (ii) to examine their relationship with in vitro embryo development, using Human Genome U133 Plus 2.0 microarrays. Genes that were upregulated in HP-hMG-treated CCs are involved in lipid metabolism (GM2A) and cell-to-cell interactions (GJA5). Conversely, genes upregulated in rFSH-treated CCs are implicated in cell assembly and organization (COL1A1 and COL3A1). Interestingly, some genes specific to each gonadotropin treatment (NPY1R and GM2A for HP-hMG; GREM1 and OSBPL6 for rFSH) were associated with day 3 embryo quality and blastocyst grade at day 5, while others (STC2 and PTX3) were related to in vitro embryo quality in both gonadotropin treatments. These genes may prove valuable as biomarkers of in vitro embryo quality.
    BioMed research international. 01/2013; 2013:354582.
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    ABSTRACT: STUDY QUESTION: Oocyte developmental competence is altered in patients with polycystic ovary syndrome (PCOS); is gene expression in cumulus cells (CCs) from mature metaphase II oocytes of patients with PCOS altered as well? SUMMARY ANSWER: Compared with CCs from non-PCOS patients, the gene expression profile of CCs isolated from mature oocytes of patients with PCOS present alterations that could explain the abnormal folliculogenesis and reduced oocyte competence in such patients. WHAT IS KNOWN ALREADY: Abnormal mRNA expression of several members of the insulin-like growth factor (IGF) family in CCs from PCOS patients was previously reported. Moreover, the whole transcriptome has been investigated in cultured CCs from PCOS patients. STUDY DESIGN, SIZE AND DURATION: This retrospective study included six PCOS patients diagnosed following the Rotterdam Criteria and six non-PCOS patients who all underwent ICSI for male infertility in the assisted reproduction technique (ART) Department of Montpellier University Hospital, between 2009 and 2011. PARTICIPANTS/MATERIALS, SETTINGAND METHODS: CCs from PCOS and non-PCOS patients who underwent controlled ovarian stimulation (COS) were isolated mechanically before ICSI. Gene expression profiles were analysed using the microarray technology and the Significance Analysis of Microarray was applied to compare the expression profiles of CCs from PCOS and non-PCOS patients. MAIN RESULTS: The gene expression profile of CCs from patients with PCOS was significantly different from that of CCs from non-PCOS patients. Specifically, CCs from women with PCOS were characterized by abnormal expression of many growth factors, including members of the epidermal growth factor-like (EGFR, EREG and AREG) and IGF-like families (IGF1R, IGF2R, IGF2BP2 and IGFBP2), that are known to play a role in oocyte competence. In addition, mRNA transcripts of factors involved in steroid metabolism, such as CYP11A1, CYP1B1, CYP19A1 and CYP2B7P1, were deregulated in PCOS CCs, and this could explain the abnormal steroidogenesis observed in these women. Functional annotation of the differentially expressed genes suggests that defects in the transforming growth factor β and estrogen receptors signalling cascades may contribute to the reduced oocyte developmental competence in patients with PCOS. LIMITATIONS AND REASONS FOR CAUTION: Owing to the strict selection criteria (similar age, weight and reasons for ART), this study included a small sample size (six cases and six controls), and thus, further investigations using a large cohort of patients are needed to confirm these results. WIDER IMPLICATIONS OF THE FINDINGS: This study opens a new perspective for understanding the pathogenesis of PCOS. STUDY FUNDING/COMPETING INTERESTS: This work was partially supported by a grant from the Ferring Pharmaceutical. The authors of the study have no competing interests to report. TRIAL REGISTRATION NUMBER: Not applicable.
    Human Reproduction 09/2012; · 4.67 Impact Factor
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    ABSTRACT: Oocyte maturation and competence to development depends on its close relationship with cumulus cells (CCs). However, the maturation conditions of human cumulus-oocyte complexes (COCs) might affect gene expression in both oocyte and CCs. We thus compared the transcriptome profiles of CCs isolated from in vivo and in vitro matured COCs at different nuclear maturation stages. Three groups of CCs from patients who underwent ICSI were included: CCs of patients with polycystic ovary syndrome (PCOS) referred for in vitro maturation (IVM), CCs from patients with PCOS for in vivo maturation (used as controls) and CCs from normal responders referred for in vivo maturation. CCs were isolated from COCs at the germinal vesicle, metaphase I and metaphase II stages. Microarray technology was used to analyse the global gene expression and significance analysis of microarray to compare the expression profiles of CCs from COCs at different nuclear maturation stages following IVM or in vivo maturation. Selected genes were validated by RT-qPCR. In CCs isolated after IVM, genes related to cumulus expansion and oocyte maturation, such as EREG, AREG and PTX3, were down-regulated, while cell cycle-related genes were up-regulated in comparison with CCs from in vivo matured COCs from PCOS and normal responder patients. Moreover, irrespective of the stage of oocyte maturation, genes involved in DNA replication, recombination and repair were up-regulated in CCs after IVM. The CC transcriptomic signature varies according to both the oocyte maturation stage and the maturation conditions. Our findings suggest a delay in the acquisition of the mature CC phenotype following IVM, opening a new perspective for the improvement in IVM conditions.
    Human Reproduction 05/2012; 27(8):2438-47. · 4.67 Impact Factor
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    ABSTRACT: Cryopreservation is now considered as an efficient way to store human oocytes to preserve fertility. However, little is known about the effects of this technology on oocyte gene expression. The aim of this study was to examine the effect of the two cryopreservation procedures, slow freezing and vitrification, on the gene expression profile of human metaphase II (MII) oocytes. Unfertilized MII oocytes following ICSI failure were cryopreserved either by slow freezing or by the Cryotip method for vitrification. After thawing, total RNA was extracted and analyzed using Affymetrix Human Genome U133 Plus 2.0 GeneChip arrays. The gene expression profiles and associated biological pathways in slowly frozen/thawed and vitrified MII oocytes were determined and compared with those of non-cryopreserved MII oocytes used as controls. Both cryopreservation procedures negatively affected the gene expression profile of human MII oocytes in comparison with controls. However, slowly frozen and vitrified MI oocytes displayed specific gene expression signatures. Slow freezing was associated with down-regulation of genes involved in chromosomal structure maintenance (KIF2C and KIF3A) and cell cycle regulation (CHEK2 and CDKN1B) that may lead to a reduction in the oocyte developmental competence. In vitrified oocytes, many genes of the ubiquitination pathway were down-regulated, including members of the ubiquitin-specific peptidase family and subunits of the 26S proteasome. Such inhibition of the degradation machinery might stabilize the maternal protein content that is necessary for oocyte developmental competence. The low pregnancy rates commonly observed when using human MII oocytes after slow freezing-thawing may be explained by the alterations of the oocyte gene expression profile.
    Human Reproduction 05/2012; 27(7):2160-8. · 4.67 Impact Factor
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    ABSTRACT: The good folliculogenesis evolution is fundamental for the obtaining of a competent oocyte, able to lead to pregnancy, once fertilized. During the follicular development, the oocyte is in close contact with surrounding cumulus cells (CCs) to form a cumulus-oocyte complex. The bidirectional exchange between oocyte and contiguous CCs via gap junction communications and paracrine signaling is important for oocyte competence and CCs development. These reciprocal regulations are controlled by some key genes. Recently, it has been demonstrated that these genes are themselves regulated by short RNAs fragments (∼22 nucleotides), called microRNAs. The identification and the quantification in the CCs of the microRNAs regulating these genes could promote the development of non invasive tests in order to assess the oocyte quality and its ability to provide embryo with a high implantation potential. This approach could be decisive in the embryo selection to transfer and could avoid the risk of multiple pregnancies by the replacement of a single embryo.
    Gynecologie Obstetrique & Fertilite - GYNECOL OBSTET FERTIL. 03/2012;
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    ABSTRACT: In humans, successful pregnancy depends on a cascade of dynamic events during early embryonic development. Unfortunately, molecular data on these critical events is scarce. To improve our understanding of the molecular mechanisms that govern the specification/development of the trophoblast cell lineage, the transcriptome of human trophectoderm (TE) cells from day 5 blastocysts was compared to that of single day 3 embryos from our in vitro fertilization program by using Human Genome U133 Plus 2.0 microarrays. Some of the microarray data were validated by quantitative RT-PCR. The TE molecular signature included 2,196 transcripts, among which were genes already known to be TE-specific (GATA2, GATA3 and GCM1) but also genes involved in trophoblast invasion (MUC15), chromatin remodeling (specifically the DNA methyltransferase DNMT3L) and steroid metabolism (HSD3B1, HSD17B1 and FDX1). In day 3 human embryos 1,714 transcripts were specifically up-regulated. Besides stemness genes such as NANOG and DPPA2, this signature included genes belonging to the NLR family (NALP4, 5, 9, 11 and 13), Ret finger protein-like family (RFPL1, 2 and 3), Melanoma Antigen family (MAGEA1, 2, 3, 5, 6 and 12) and previously unreported transcripts, such as MBD3L2 and ZSCAN4. This study provides a comprehensive outlook of the genes that are expressed during the initial embryo-trophectoderm transition in humans. Further understanding of the biological functions of the key genes involved in steroidogenesis and epigenetic regulation of transcription that are up-regulated in TE cells may clarify their contribution to TE specification and might also provide new biomarkers for the selection of viable and competent blastocysts.
    PLoS ONE 01/2012; 7(6):e39306. · 3.53 Impact Factor
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    ABSTRACT: The adult mammalian cochlea lacks regenerative ability and the irreversible degeneration of cochlear sensory hair cells leads to permanent hearing loss. Previous data show that early postnatal cochlea harbors stem/progenitor-like cells and shows a limited regenerative/repair capacity. These properties are progressively lost later during the postnatal development. Little is known about the genes and pathways that are potentially involved in this difference of the regenerative/repair potentialities between early postnatal and adult mammalian cochlear sensory epithelia (CSE). The goal of our study is to investigate the transcriptomic profiles of these two stages. We used Mouse Genome 430 2.0 microarray to perform an extensive analysis of the genes expressed in mouse postnatal day-3 (P3) and adult CSE. Statistical analysis of microarray data was performed using SAM (Significance Analysis of Microarrays) software. We identified 5644 statistically significant differentially expressed transcripts with a fold change (FC) >2 and a False Discovery Rate (FDR) ≤0.05. The P3 CSE signature included 3,102 transcripts, among which were known genes in the cochlea, but also new transcripts such as, Hmga2 (high mobility group AT-hook 2) and Nrarp (Notch-regulated ankyrin repeat protein). The adult CSE overexpressed 2,542 transcripts including new transcripts, such as Prl (Prolactin) and Ar (Androgen receptor), that previously were not known to be expressed in the adult cochlea. Our comparative study revealed important genes and pathways differentially expressed between the developing and adult CSE. The identification of new candidate genes would be useful as potential markers of the maintenance or the loss of stem cells and regenerative/repair ability during mammalian cochlear development.
    PLoS ONE 01/2012; 7(8):e42987. · 3.53 Impact Factor
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    ABSTRACT: The good folliculogenesis evolution is fundamental for the obtaining of a competent oocyte, able to lead to pregnancy, once fertilized. During the follicular development, the oocyte is in close contact with surrounding cumulus cells (CCs) to form a cumulus-oocyte complex. The bidirectional exchange between oocyte and contiguous CCs via gap junction communications and paracrine signaling is important for oocyte competence and CCs development. These reciprocal regulations are controlled by some key genes. Recently, it has been demonstrated that these genes are themselves regulated by short RNAs fragments (approximately 22 nucleotides), called microRNAs. The identification and the quantification in the CCs of the microRNAs regulating these genes could promote the development of non invasive tests in order to assess the oocyte quality and its ability to provide embryo with a high implantation potential. This approach could be decisive in the embryo selection to transfer and could avoid the risk of multiple pregnancies by the replacement of a single embryo.
    Gynécologie Obstétrique & Fertilité 12/2011; 40(3):170-3. · 0.55 Impact Factor
  • PLoS ONE 11/2011; · 3.53 Impact Factor
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    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.
    Reproductive biomedicine online 09/2011; 24(1):23-34. · 2.68 Impact Factor
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    ABSTRACT: The trophoblast cell lineage is specified early at the blastocyst stage, leading to the emergence of the trophectoderm and the pluripotent cells of the inner cell mass. Using a double mRNA amplification technique and a comparison with transcriptome data on pluripotent stem cells, placenta, germinal and adult tissues, we report here some essential molecular features of the human mural trophectoderm. In addition to genes known for their role in placenta (CGA, PGF, ALPPL2 and ABCG2), human trophectoderm also strongly expressed Laminins, such as LAMA1, and the GAGE Cancer/Testis genes. The very high level of ABCG2 expression in trophectoderm, 7.9-fold higher than in placenta, suggests a major role of this gene in shielding the very early embryo from xenobiotics. Several genes, including CCKBR and DNMT3L, were specifically up-regulated only in trophectoderm, indicating that the trophoblast cell lineage shares with the germinal lineage a transient burst of DNMT3L expression. A trophectoderm core transcriptional regulatory circuitry formed by 13 tightly interconnected transcription factors (CEBPA, GATA2, GATA3, GCM1, KLF5, MAFK, MSX2, MXD1, PPARD, PPARG, PPP1R13L, TFAP2C and TP63), was found to be induced in trophectoderm and maintained in placenta. The induction of this network could be recapitulated in an in vitro trophoblast differentiation model.
    Stem cell reviews 07/2011; 8(1):150-62. · 5.08 Impact Factor
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    ABSTRACT: Pluripotent stem cells (PSC) are functionally characterized by their capacity to differentiate into all the cell types from the three germ layers. A wide range of markers, the expression of which is associated with pluripotency, has been used as surrogate evidence of PSC pluripotency, but their respective relevance is poorly documented. Here, we compared by polychromatic flow cytometry the kinetics of loss of expression of eight widely used pluripotency markers (SSEA3, SSEA4, TRA-1-60, TRA-1-81, CD24, OCT4, NANOG, and alkaline phosphatase [AP]) at days 0, 5, 7, and 9 after induction of PSC differentiation into cells representative of the three germ layers. Strikingly, each marker showed a different and specific kinetics of disappearance that was similar in all the PSC lines used and for all the induced differentiation pathways. OCT4, SSEA3, and TRA-1-60 were repeatedly the first markers to be downregulated, and their expression was completely lost at day 9. By contrast, AP activity, CD24, and NANOG proteins were still detectable at day 9. In addition, we show that differentiation markers are coexpressed with pluripotency markers before the latter begin to disappear. These results suggest that OCT4, SSEA3, and TRA-1-60 might be better to trace in vitro the emergence of pluripotent cells during reprogramming.
    Stem Cells 06/2011; 29(9):1469-74. · 7.70 Impact Factor
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    ABSTRACT: Crosstalk between human trophectoderm (TE) and endometrial cells during the implantation window is a complex and not well-understood process. The aims of this study were (i) to evaluate the global gene expression profile in TE cells from Day 5 human blastocysts issued from IVF, (ii) to compare these data with the transcriptomic profile of endometrial cells in stimulated cycles for IVF and (iii) to identify potential early dialogues between maternal and embryonic cells during the implantation window. Endometrial biopsies (n = 18) from normal responder patients were performed on the day of embryo transfer (Day 5 after human chorionic gonadotrophin administration). TE biopsies from five blastocysts donated for research purposes were mechanically extracted. DNA microarray analysis was carried out to identify the specific gene expression profiles and the biological pathways activated during the implantation window in endometrial and TE cells. Several cytokines (such as PDGFA, placenta growth factor, IGF2BP1 and IGF2BP3) were up-regulated in human TE cells, whereas some of the corresponding receptors (PDGFRA and KDR) were over-expressed in the receptive endometrium, suggesting that these molecules are involved in the early dialogue between blastocyst and maternal endometrial cells. In addition, several adhesion molecules and extracellular matrix proteins (MCAM, ITGAE and LAMA1) were also over-expressed in the TE, while others (ALCAM, CEACAM1, PECAM1, ITGB8 and LAMA2) were restricted to the receptive endometrium. The present study shows that several growth factors, cytokines, integrins and adhesion molecules are expressed in the TE and endometrium at the time of implantation. These results could contribute to the understanding of the mechanisms involved in the early dialogue between blastocyst and endometrium during implantation. Such results should be confirmed by further studies.
    Human Reproduction 03/2011; 26(6):1440-9. · 4.67 Impact Factor

Publication Stats

989 Citations
178.76 Total Impact Points

Institutions

  • 2012–2014
    • Université de Montpellier 1
      Montpelhièr, Languedoc-Roussillon, France
  • 2005–2013
    • Centre Hospitalier Universitaire de Montpellier
      • Institute for Research in Biotherapy (IRB)
      Montpelhièr, Languedoc-Roussillon, France
  • 2007–2012
    • Institut de Recherche en Cancerologie de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 2005–2010
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2009
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France