Genomic Assessment of Human Cumulus Cell Marker Genes as Predictors of Oocyte Developmental Competence: Impact of Various Experimental Factors

INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France.
PLoS ONE (Impact Factor: 3.23). 07/2012; 7(7):e40449. DOI: 10.1371/journal.pone.0040449
Source: PubMed


Single embryo transfer (SET) is the most successful way to reduce the frequency of multiple pregnancies following in vitro fertilisation. However, selecting the embryo for SET with the highest chances of pregnancy remains a difficult challenge since morphological and kinetics criteria provide poor prediction of both developmental and implantation ability. Partly through the expression of specific genes, the oocyte-cumulus interaction helps the oocyte to acquire its developmental competence. Our aim was therefore to identify at the level of cumulus cells (CCs) genes related to oocyte developmental competence.

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Available from: Vincent Puard, Aug 13, 2014
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    • "Its statistical relevance was evaluated by the Fisher's exact test. Besides, among the results, the ability of the targeted output cluster to statistically discriminate between experimental conditions (stress vs. control) was evaluated by the Fisher's exact test as previously described (Feuerstein et al. 2012). Currently, the database contains the datasets from 355 microarray experiments from public and private repositories (listed in Supplemental Table A1) up to April 2013, which were conducted on zebrafish (Danio rerio, H.) (188 datasets), European sea bass (Dicentrarchus labrax, L.) (four datasets), Atlantic cod (Gadus morhua, L.) (five datasets), longjaw mudsucker (Gillichthys mirabilis, C.) (four datasets), rainbow trout (Oncorhynchus mykiss, W.) (73 datasets), Atlantic salmon (Salmo salar, L.) (60 datasets), and gilthead sea bream (21 datasets). "
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    ABSTRACT: The effects of nutrient availability on the transcriptome of cardiac and skeletal muscle tissues were assessed in juvenile gilthead sea bream fed with a standard diet at two feeding levels: (1) full ration size and (2) 70 % satiation followed by a finishing phase at the maintenance ration. Microarray analysis evidenced a characteristic transcriptomic profile for each muscle tissue following changes in oxidative capacity (heart > red skeletal muscle > white skeletal muscle). The transcriptome of heart and secondly that of red skeletal muscle were highly responsive to nutritional changes, whereas that of glycolytic white skeletal muscle showed less ability to respond. The highly expressed and nutritionally regulated genes of heart were mainly related to signal transduction and transcriptional regulation. In contrast, those of white muscle were enriched in gene ontology (GO) terms related to proteolysis and protein ubiquitination. Microarray meta-analysis using the bioinformatic tool Fish and Chips ( ) showed the close association of a representative cluster of white skeletal muscle with some of cardiac and red skeletal muscle, and many GO terms related to mitochondrial function appeared to be common links between them. A second round of cluster comparisons revealed that mitochondria-related GOs also linked differentially expressed genes of heart with those of liver from cortisol-treated gilthead sea bream. These results show that mitochondria are among the first responders to environmental and nutritional stress stimuli in gilthead sea bream, and functional phenotyping of this cellular organelle is highly promising to obtain reliable markers of growth performance and well-being in this fish species.
    Full-text · Article · Mar 2014 · Marine Biotechnology
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    • "The oocyte-cumulus interaction through the expression of specific genes helps the oocyte to acquire its developmental competence. Using microarrays Feuerstein et al. [17] attempted to determine genes related to oocyte developmental competence. Gene expression of oocytecumulus was studied according to the nuclear maturity of the oocyte (immature versus mature oocyte) and to the developmental competence of the oocyte (ability to reach the blastocyst stage after fertilisation). "
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    ABSTRACT: The quality of follicular oocytes depends on interactions with surrounding granulosa cells. Development of molecular techniques and methods enables better understanding of processes underlying mammalian reproduction on cellular level. The success in reproductive biology and medicine in different species depends on reliable assessment of oocyte and embryo viability which presently mainly bases on embryo morphology. Although successful pregnancies have been achieved using this approach, its precision still should be improved and completed with other, more objective, and accurate assessment strategies. Global profiling of gene expression in follicular cumulus cells using microarrays is continuously leading to the establishment of new biomarkers which can be used to select oocytes with highest developmental potential. Even more potential applications and greater precision could be achieved using next generation sequencing (NGS) of granulosa and cumulus cell RNA (RNA-seq). However, due to the high cost, this method is not used as frequently as microarrays at the moment. In any case, high-throughput technologies offer the possibilities and advantages in ovarian somatic cell analysis on scale that has not been noted so far. The aim of this work is to present current directions and examples of global molecular profiling of granulosa cells and underline its impact on reproductive biology and medicine.
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    • "Some researchers have considered that cumulus cell function may be a more major determinant than the oocyte itself of the quality of the mitochondria in the activated oocytes. In elegant studies undertaken to determine which cumulus genes were both induced by the LH peak and critical to oocyte competence, mRNA expression in cumulus cells was prospectively studied in human oocytes that would be used for intracytoplasmic sperm injection [14]. Gene functions that were up-regulated in cumulus cells were identified in mature oocytes (meiosis II compared to Germinal vesicle (GV) stage cells) and those that were up-regulated in cumulus cells from mature oocytes that yielded a blastocyst at day 5/6 of in vitro culture. "
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    ABSTRACT: Infertility, spontaneous abortion and conception of trisomic offspring increase exponentially with age in mammals but in women there is an apparent acceleration in the rate from about age 37. The problems mostly commonly occur when the ovarian pool of follicles is depleted to a critical level with age but are also found in low follicular reserve of other etiologies. Since recent clinical studies have indicated that dehydroepiandrosterone (DHEA) supplementation may reverse the problem of oocyte quality, this review of the literature was undertaken in an attempt to find an explanation of why this is effective? In affected ovaries, oxygenation of follicular fluid is low, ultrastructural disturbances especially of mitochondria, occur in granulosa cells and oocytes, and considerable disturbances of meiosis occur. There is, however, no evidence to date that primordial follicles are compromised. In females with normal fertility, pre-antral ovarian theca cells respond to stimulation by inhibin B to provide androgen-based support for the developing follicle. With depletion of follicle numbers, inhibin B is reduced with consequent reduction in theca DHEA. Theca cells are the sole ovarian site of synthesis of DHEA, which is both a precursor of androstenedione and an essential ligand for peroxisome proliferator-activated receptor alpha (PPARα), the key promoter of genes affecting fatty acid metabolism and fat transport and genes critical to mitochondrial function. As well as inducing a plethora of deleterious changes in follicular cytoplasmic structure and function, the omega 9 palmitate/oleate ratio is increased by lowered activity of PPARα. This provides conditions for increased ceramide synthesis and follicular loss through ceramide-induced apoptosis is accelerated. In humans critical theca DHEA synthesis occurs at about 70 days prior to ovulation thus effective supplementation needs to be undertaken about four months prior to intended conception; timing which is also suggested by successful interventions to date. In humans and primates that undergo adrenarche, the adrenal zona reticularis (ZR) is the major site of DHEA production, however this is also reduced with age. Concomitant loss in function of the ZR might account for the acceleration in the rate of aging seen in humans in the late thirties’ age group.
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