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Altmae S.,Competence Center on Reproductive Medicine and Biology | Altmae S.,University of Granada | Martinez-Conejero J.A.,IVIOMICS | Esteban F.J.,University of Jaen | And 5 more authors.
Reproductive Sciences | Year: 2013

MicroRNAs (miRNAs) act as important epigenetic posttranscriptional regulators of gene expression. We aimed to gain more understanding of the complex gene expression regulation of endometrial receptivity by analyzing miRNA signatures of fertile human endometria. We set up to analyze miRNA signatures of receptive (LH + 7, n = 4) versus prereceptive (LH + 2, n = 5) endometrium from healthy fertile women. We found hsa-miR-30b and hsa-miR-30d to be significantly upregulated, and hsa-miR-494 and hsa-miR-923 to be downregulated in receptive endometrium. Three algorithms (miRanda, PicTar, and TargetScan) were used for target gene prediction. Functional analyses of the targets using Ingenuity Pathways Analysis and The Database for Annotation, Visualization and Integrated Discovery indicated roles in transcription, cell proliferation and apoptosis, and significant involvement in several relevant pathways, such as axon guidance, Wnt/β-catenin, ERK/MAPK, transforming growth factor β (TGF-β), p53 and leukocyte extravasation. Comparison of predicted miRNA target genes and our previous messenger RNA microarray data resulted in a list of 12 genes, including CAST, CFTR, FGFR2, and LIF that could serve as a panel of genes important for endometrial receptivity. In conclusion, we suggest that a subset of miRNAs and their target genes may play important roles in endometrial receptivity. © 2013 The Author(s).

Altmae S.,Competence Center on Reproductive Medicine and Biology | Altmae S.,University of Granada | Esteban F.J.,University of Jaen | Stavreus-Evers A.,Uppsala University | And 14 more authors.
Human Reproduction Update | Year: 2014

Background: 'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising fromthe vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data.With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data. methods: Systematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013. results: The current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies. conclusion: A highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Altmae S.,Karolinska University Hospital | Altmae S.,Competence Center on Reproductive Medicine and Biology | Hovatta O.,Karolinska University Hospital | Stavreus-Evers A.,Uppsala University | And 2 more authors.
Human Reproduction Update | Year: 2011

Background: Nowadays, the use of IVF has improved the prospects of infertility treatment. The expected outcome of IVF depends greatly on the effectiveness of controlled ovarian hyperstimulation (COH), where exogenous gonadotrophins are used to induce folliculogenesis. The response to stimulation varies substantially among women and is difficult to predict. Several predictive markers of COH outcome have been proposed (e.g. maternal age and ovarian reserve), but the search for optimal predictors is ongoing. Pharmacogenetic studies demonstrate the effects of individual genetic variability on COH outcome and the potential for customizing therapy based on the patient's genome. Methods: MEDLINE, EMBASE, DARE, CINAHL and the Cochrane Library, and references from relevant articles were investigated up to February 2011 regarding any common genetic variation and COH/IVF outcome. Results: Several polymorphisms in genes involved in FSH signalling, estrogen biosynthesis, folliculogenesis, folatemetabolismand other aspects influence the response to exogenous gonadotrophin administration, resulting in differences in COH and IVF outcomes. Nevertheless, the most studied polymorphism FSHR Asn680Ser is practically the only genetic marker, together with ESR1 PvuII T/C, that could be applied in clinical tests. Conclusions: Although data are accumulating with evidence suggesting that the ovarian response to COH is mediated by various polymorphisms, the optimal biomarkers and the efficacy of the tests still remain to be evaluated. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Altmae S.,Karolinska University Hospital | Altmae S.,Competence Center on Reproductive Medicine and Biology | Salumets A.,Competence Center on Reproductive Medicine and Biology
Reproductive BioMedicine Online | Year: 2011

Male factor infertility is a growing problem worldwide. Considering that a male factor is involved in at least 20% of infertility cases, there is a need for better predictive markers of sperm function. The traditional sperm analysis based on sperm count and motility has been used for the diagnosis of male fertility for several decades, however, a significant number of men with normal sperm features remain unable to reach pregnancy. This fact clearly indicates the need to develop new male infertility tests to accurately diagnose the sperm samples from these individuals. Furthermore, the classic spermiogram has limited predictive power to predict pregnancy in assisted reproductive techniques. Microarray technology is a powerful tool for detecting gene expression of thousands of genes at the same time. There is a great interest in the sperm transcriptome as a source from which to develop markers of male infertility. This commentary discusses the current advances in the microarray technology and sperm quality. It is believed that microarray-based fertility testing of sperm potential in infertility treatment could be close at hand. © 2011, Reproductive Healthcare Ltd. All rights reserved.

Tontson L.,University of Tartu | Kopanchuk S.,University of Tartu | Kopanchuk S.,Competence Center on Reproductive Medicine and Biology | Rinken A.,University of Tartu | Rinken A.,Competence Center on Reproductive Medicine and Biology
Neurochemistry International | Year: 2014

Bodipy-FL-NAN-190 was found to be well suited for characterization of ligand binding to 5-HT1A receptors expressed in budded baculovirus particles, as binding is accompanied by large increases in fluorescence intensity and anisotropy. This ligand appears to bind rapidly (t 1/2,ass < 1 min), reversibly (t1/2,diss ∼ 6 min) and has high affinity (Kd = 0.30 ± 0.13 nM). This fluorescence anisotropy assay based on Bodipy-FL-NAN-190 binding to baculovirus particles was also a suitable assay system for the pharmacological characterization of non-labelled serotonergic ligands, as well as being sensitive to the presence of G-proteins and guanine nucleotides. Coexpression of αi subunits of human G-proteins in baculovirus particles resulted in the appearance of significantly greater proportion of nucleotide sensitive high affinity agonist binding sites. There were no significant differences between αi1 and αi3 subtypes, while ligand binding in the presence of αi2 had higher sensitivity to GDP and Mn2+.© 2014 Elsevier B.V.

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