Gene expression profiles of cumulus cells obtained from women treated with recombinant human luteinizing hormone + recombinant human follicle-stimulating.

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Presentation transcript:

Gene expression profiles of cumulus cells obtained from women treated with recombinant human luteinizing hormone + recombinant human follicle-stimulating hormone or highly purified human menopausal gonadotropin versus recombinant human follicle-stimulating hormone alone Valentina Gatta, Ph.D., Carla Tatone, Ph.D., Rosanna Ciriminna, B.Sc., Marilena Vento, B.Sc., Sara Franchi, M.T., Marco d'Aurora, B.Sc., Samantha Sperduti, B.Sc., Vito Cela, Ph.D., Placido Borzì, M.D., Roberto Palermo, M.D., Liborio Stuppia, M.D., Paolo Giovanni Artini, Ph.D. Fertility and Sterility Volume 99, Issue 7, Pages 2000-2008.e1 (June 2013) DOI: 10.1016/j.fertnstert.2013.01.150 Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Hierarchic clustering analysis of the dataset originated from a total of six experiments carried out on RNA extracted from cumulus-oocyte cells obtained from women treated for ovarian stimulation with r-hLH + r-hFSH or hp-hMG versus r-hFSH alone (control). The cluster analysis shows the presence of four different clusters (1–4) composed respectively of 84, 61, 53, and 11 transcripts. All the relevant genes are grouped according to their expression values shown as log ratios (gene expression as the value obtained in the r-hLH + r-hFSH or hp-hMG treatments divided by the value of the r-hFSH treatment as control). Each row corresponds to one gene, each column to six different microarray experiments. The quantitative changes in gene expression across all the samples are represented in color: red indicates overexpressed genes, and green indicates down-regulated genes. Black bars indicate no changes in expression. Missing data points are represented as gray bars. The labels above the columns indicate the different treatments. Fertility and Sterility 2013 99, 2000-2008.e1DOI: (10.1016/j.fertnstert.2013.01.150) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Ingenuity Pathways Assessment (IPA) functional analysis of the cluster 1 dataset genes. (A) Key functions associated with genes found to be down-regulated after stimulation treatment with hp-hMG and up-regulated after r-hLH + r-hFSH administration compared with control. (B) Key functions associated with genes found to be down-regulated after the use of r-hLH + r-hFSH and up-regulated after treatment with hp-hMG compared with control. Fertility and Sterility 2013 99, 2000-2008.e1DOI: (10.1016/j.fertnstert.2013.01.150) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Network generated by Ingenuity Pathways Assessment analysis associated with the cluster 1. Genes in gray are down-regulated after the use of r-hLH + r-hFSH and up-regulated after treatment with hp-hMG compared with control. Genes in white are not modulated by treatments. Arrows indicate that a molecule acts on another, and lines without arrows indicate that a molecule binds to another. Fertility and Sterility 2013 99, 2000-2008.e1DOI: (10.1016/j.fertnstert.2013.01.150) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 Validation microarray gene expression data by quantitative reverse-transcription polymerase chain reaction. Analysis of the selected genes (A) AKT3, (B) IL11, (C) RXRB, (D) DNase, (E) MAPK6, and (F) RAD50 was carried out on the RNA pools obtained from the cumulus cells of the patients treated with r-hFSH, hp-hMG, and r-hLH + r-hFSH, respectively. Data are the means ± SD of three independent experiments in triplicate (*P<.01; Student t test). Fertility and Sterility 2013 99, 2000-2008.e1DOI: (10.1016/j.fertnstert.2013.01.150) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions