Microarray technology provides a unique opportunity to examine gene expression patterns in human embryonic stem cells (hESCs). We performed a meta-analysis of 38 original studies reporting on the transcriptome of hESCs. We determined that 1,076 genes were found to be overexpressed in hESCs by at least three studies when compared to differentiated cell types, thus composing a "consensus hESC gene list." Only one gene was reported by all studies: the homeodomain transcription factor POU5F1/ OCT3/4. The list comprised other genes critical for pluripotency such as the transcription factors NANOG and SOX2, and the growth factors TDGF1/CRIPTO and Galanin. We show that CD24 and SEMA6A, two cell surface protein-coding genes from the top of the consensus hESC gene list, display a strong and specific membrane protein expression on hESCs. Moreover, CD24 labeling permits the purification by flow cytometry of hESCs cocultured on human fibroblasts. The consensus hESC gene list also included the FZD7 WNT receptor, the G protein-coupled receptor GPR19, and the HELLS helicase, which could play an important role in hESCs biology. Conversely, we identified 783 genes downregulated in hESCs and reported in at least three studies. This "consensus differentiation gene list" included the IL6ST/GP130 LIF receptor. We created an online hESC expression atlas, http:// amazonia.montp.inserm.fr, to provide an easy access to this public transcriptome dataset. Expression histograms comparing hESCs to a broad collection of fetal and adult tissues can be retrieved with this web tool for more than 15,000 genes. STEM CELLS 2007;25:961-973 Disclosure of potential conflicts of interest is found at the end of this article.

The identification of genes that were up- and down-regulated during oocyte maturation greatly improves our understanding of oocyte biology and will provide new markers that signal viable and competent oocytes. Furthermore, genes found expressed in cumulus cells are potential markers of granulosa cell tumours.

Gonadotrophin treatments in COS cycles led to disruptions of the transcriptional activation of genes involved in normal endometrial receptivity. We propose that when the receptiveness of the endometrium is seriously compromised by the COS protocol, fresh embryo replacement should be cancelled, the embryo frozen and thawed embryo replacement should be performed under natural cycles.

BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.

Single-embryo transfer is becoming increasingly common in in vitro fertilization (IVF) treatment as a means of reducing multiple pregnancy rates leading to a higher incidence of medical, perinatal and neonatal complications. Consequently, selecting embryos with the highest implantation potential is of great importance in assisted reproductive technology. To date, the choice of the best embryos to transfer is based on subjective morphological parameters. However, as judged by their subjective aspect, movement towards more sophisticated technologies to select the most competent oocytes and/or embryos with the greatest implantation potential have become available, including emerging 'omics' sciences, such as genomics, transcriptomics, proteomics and metabolomics. In this way, the study of the cumulus cells (CCs) transcriptomic profile offers the opportunity, by a non-invasive method, to predict oocyte and embryo competence because bidirectional traffic between CCs and the oocyte is very important for the acquisition of this competence. Using either RT-PCR or DNA microarrays, some studies have provided evidence for the genes expressed in CCs presenting potential biomarkers to predict embryo quality and pregnancy outcomes. This review provides an overview of the current knowledge about CCs as biomarkers for oocyte and embryo selection under an IVF program.

Identification of new criteria for embryo quality is required to improve the clinical outcome of in vitro fertilization. The aim of this study was to determine the gene expression profile of cumulus cells (CC) surrounding the oocyte as biomarkers for embryo potential and to identify genes to be used as prognostic indicators of successful pregnancy. CC from single oocytes were analysed using DNA microarrays. Gene expression profiles of CC surrounding the oocyte associated with good embryonic quality and pregnancy outcome were computed. We observed that CC issued from oocytes that developed into embryos with a good morphology had differing gene expression profile according to the pregnancy outcome of the embryo. We demonstrated that the expression of BCL2L11, PCK1 and NFIB in CC is significantly correlated with embryo potential and successful pregnancy. These results were confirmed by quantitative RT-PCR. The gene expression profiling of human CC correlates with embryo potential and pregnancy outcome. BCL2L11, PCK1 and NFIB genes are proposed as biomarkers for predicting pregnancy. Our findings suggest a non-invasive approach, offering a new potential strategy for competent embryo selection. This approach should be validated in single-embryo transfer programmes.

Background: The first week of human pre-embryo development is characterized by the induction of totipotency and then pluripotency. The understanding of this delicate process will have far reaching implication for in vitro fertilization and regenerative medicine. Human mature MII oocytes and embryonic stem (ES) cells are both able to achieve the feat of cell reprogramming towards pluripotency, either by somatic cell nuclear transfer or by cell fusion, respectively. Comparison of the transcriptome of these two cell types may highlight genes that are involved in pluripotency initiation.

One of the major unresolved questions with male infertility is the identification of the molecular origin of a great majority of the spermatogenetic arrests currently diagnosed as idiopathic male infertility. During the past years, several families of regulating factors have been implicated in spermatogenesis defects observed essentially in animal models. Among these factors are signalling molecules, and particularly the stem cell factor (SCF)/c-kit system. The SCF and its receptor c-kit are an appropriate example to illustrate the role of signalling molecules in the physiology and pathology of spermatogenesis. The SCF/c-kit regulates primordial germ cell migration, proliferation and apoptosis during fetal gonadal development. The SCF/c-kit also regulates spermatogonia proliferation in the adult animal. In mutant mice, abnormalities of the SCF/c-kit gene expression, such as gene deletion, point mutation, alternative splicing defect, lead to different types of spermatogenesis alterations (e.g. decrease in primordial germ cell migration, decrease in spermatogonia proliferation). More recently, defects in SCF/c-kit gene expression have also been shown in human testicular dysfunctions. Indeed, a reduction in SCF/c-kit expression has been evidenced in oligozoospermia/azoospermia associated with an increase in the germ cell apoptosis process. In addition, c-kit seems to be a good marker of seminoma testicular tumours. This review reports a large number of data--obtained essentially in animal models--that suggest an important role for the SCF/c-kit system in spermatogenesis and, as a corollary, its potential involvement in spermatogenic defects.