S. Assou

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

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Publications (86)328.65 Total impact

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    ABSTRACT: Pluripotency is at the crossroads of stem cell research and biology of reproduction. The mature metaphase II oocyte contains the key factors for pluripotency induction and maintenance as assessed by its capacity to reprogram somatic nuclei. The cumulus cells (CCs) niche that surrounds the oocyte is crucial for its maturation and presumably for the oocyte to acquire its competence to confer pluripotency. In this study, we examined whether cells cultured from the human mature metaphase II oocyte CCs niche (hCC) could be used as feeders for the propagation of human induced pluripotent stem cells (hiPSCs). The iPS cells cultured on hCC (hCC-iPS) were assessed for their pluripotency potential by their expression of pluripotency-associated genes such as Oct4, Nanog, and TRA1-60 and their competence to differentiate into the three germ layers in vitro (embryoid bodies) as well as in vivo (teratoma formation). We show that not only the hCC-iPS cells maintained their pluripotency potential but they also exhibited much better self-renewal performance in terms of proliferation rate compared to the same cells cultured on human foreskin fibroblast (hFF) feeders (hFF-iPS). A comparative gene expression profile study of hCC and hFF revealed significant differences (p<0.05) in expression of cellular matrix components and an up regulation in hCC of genes known to be important players in cell proliferation such as interleukin 6 gene (IL6).
    Stem Cells and Development 06/2015; DOI:10.1089/scd.2015.0043 · 3.73 Impact Factor
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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. DOI:10.1016/j.gyobfe.2014.09.006 · 0.52 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 10/2014; 83(4). DOI:10.1016/j.mehy.2014.08.019 · 1.07 Impact Factor
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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 09/2014; 2014:964614. DOI:10.1155/2014/964614 · 2.71 Impact Factor
  • Fertility and Sterility 09/2014; 102(3):e215. DOI:10.1016/j.fertnstert.2014.07.725 · 4.59 Impact Factor
  • Fertility and Sterility 09/2014; 102(3):e116-e117. DOI:10.1016/j.fertnstert.2014.07.401 · 4.59 Impact Factor
  • Fertility and Sterility 09/2014; 102(3):e114. DOI:10.1016/j.fertnstert.2014.07.393 · 4.59 Impact Factor
  • Fertility and Sterility 09/2014; 102(3):e127. DOI:10.1016/j.fertnstert.2014.07.435 · 4.59 Impact Factor
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    ABSTRACT: BACKGROUND 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; 20(6). DOI:10.1093/humupd/dmu031 · 10.17 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 04/2014; 2014:951937. DOI:10.1155/2014/951937 · 3.17 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; 21(11). DOI:10.2174/09298673113206660278 · 3.85 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.
    09/2013; 2013:354582. DOI:10.1155/2013/354582
  • Fertility and Sterility 09/2013; 100(3):S147. DOI:10.1016/j.fertnstert.2013.07.1548 · 4.59 Impact Factor
  • Fertility and Sterility 09/2013; 100(3):S471. DOI:10.1016/j.fertnstert.2013.07.449 · 4.59 Impact Factor
  • I. Boumela · D. Haouzi · S. Assou · S. Traver · S. Hamamah
    Fertility and Sterility 09/2013; 100(3):S243. DOI:10.1016/j.fertnstert.2013.07.1228 · 4.59 Impact Factor
  • Fertility and Sterility 09/2013; 100(3):S49-S50. DOI:10.1016/j.fertnstert.2013.07.1830 · 4.59 Impact Factor
  • Fertility and Sterility 09/2013; 100(3):S231. DOI:10.1016/j.fertnstert.2013.07.1261 · 4.59 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; 28(11). DOI:10.1093/humrep/det321 · 4.57 Impact Factor
  • D Haouzi · S Assou · C Monzo · C Vincens · H Dechaud · S Hamamah
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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; 27(12). DOI:10.1093/humrep/des325 · 4.57 Impact Factor
  • Fertility and Sterility 09/2012; 98(3):S154-S155. DOI:10.1016/j.fertnstert.2012.07.571 · 4.59 Impact Factor

Publication Stats

1k Citations
328.65 Total Impact Points


  • 2006–2014
    • Université de Montpellier 1
      Montpelhièr, Languedoc-Roussillon, France
  • 2008–2012
    • Institut de Recherche en Cancerologie de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 2007–2011
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2005
    • Centre Hospitalier Universitaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France