title: Effect of single post-ovulatory administration of mifepristone (RU486) on transcript profile during the receptive period in human endometrium.
abstract: Progesterone regulates uterine function during the luteal phase and is essential for the acquisition of endometrial receptivity. The objective of the present study was to identify endometrial transcripts whose expression is altered during the window of implantation after the administration of 200 mg of the antiprogestin mifepristone, 48 h after the LH peak (LH+2, LH+0=LH peak), and to determine the relationship of these transcripts with those regulated during the acquisition of receptivity. Endometrial samples were obtained in LH+7 from seven women of proven fertility, each one contributing with one cycle treated with placebo and another with mifepristone. Additionally, endometrial samples were obtained in LH+2 and LH+7 during a single untreated spontaneous cycle from seven normal fertile women as a reference. DNA microarrays were used to identify transcripts significantly regulated (defined as ≥ 2.0-fold change with false discovery rate below 1% using t-test) with the administration of mifepristone vs placebo, or during the transition from pre-receptive to receptive (LH+2 vs LH+7). Approximately 2000 transcripts were significantly regulated in both comparisons (mifepristone vs placebo and LH+2 vs LH+7), but only 777 of them were coincident and displayed opposite regulation except for 25. The mRNA level for eight selected genes regulated by mifepristone was confirmed by real-time RT-PCR. We conclude that not all changes in endometrial transcript levels occurring in the transition from LH+2 to LH+7 seem to be regulated by the progesterone receptor and ∼ 37% of the genes whose transcript levels changed by effect of mifepristone could be associated with the acquisition of receptivity.
authors.forename: Catherina A
authors.initials: CA
authors.lastname: Cuevas
authors.affiliation: Universidad de Santiago de ChileSantiago, ChileInstitute for Maternal and Child Research (IDIMI), Universidad de ChileCorreo226-3, Santiago, ChileInstituto Chileno de Medicina Reproductiva (ICMER)Santiago, ChileLaboratory of Molecular Technology, National Cancer Institute-Science Applications International CorporationFrederick, Maryland, USAFacultad de Medicina,Center for Integrative Medicine and Innovative Science (CIMIS), Universidad Andres BelloSantiago, Chile atapiap@med.uchile.cl.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tapia-Pizarro
authors.affiliation: Universidad de Santiago de ChileSantiago, ChileInstitute for Maternal and Child Research (IDIMI), Universidad de ChileCorreo226-3, Santiago, ChileInstituto Chileno de Medicina Reproductiva (ICMER)Santiago, ChileLaboratory of Molecular Technology, National Cancer Institute-Science Applications International CorporationFrederick, Maryland, USAFacultad de Medicina,Center for Integrative Medicine and Innovative Science (CIMIS), Universidad Andres BelloSantiago, Chile.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Salvatierra
authors.affiliation: Universidad de Santiago de ChileSantiago, ChileInstitute for Maternal and Child Research (IDIMI), Universidad de ChileCorreo226-3, Santiago, ChileInstituto Chileno de Medicina Reproductiva (ICMER)Santiago, ChileLaboratory of Molecular Technology, National Cancer Institute-Science Applications International CorporationFrederick, Maryland, USAFacultad de Medicina,Center for Integrative Medicine and Innovative Science (CIMIS), Universidad Andres BelloSantiago, Chile.
authors.forename: David J
authors.initials: DJ
authors.lastname: Munroe
authors.affiliation: Universidad de Santiago de ChileSantiago, ChileInstitute for Maternal and Child Research (IDIMI), Universidad de ChileCorreo226-3, Santiago, ChileInstituto Chileno de Medicina Reproductiva (ICMER)Santiago, ChileLaboratory of Molecular Technology, National Cancer Institute-Science Applications International CorporationFrederick, Maryland, USAFacultad de Medicina,Center for Integrative Medicine and Innovative Science (CIMIS), Universidad Andres BelloSantiago, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Velasquez
authors.affiliation: Universidad de Santiago de ChileSantiago, ChileInstitute for Maternal and Child Research (IDIMI), Universidad de ChileCorreo226-3, Santiago, ChileInstituto Chileno de Medicina Reproductiva (ICMER)Santiago, ChileLaboratory of Molecular Technology, National Cancer Institute-Science Applications International CorporationFrederick, Maryland, USAFacultad de Medicina,Center for Integrative Medicine and Innovative Science (CIMIS), Universidad Andres BelloSantiago, Chile.
authors.forename: Horacio B
authors.initials: HB
authors.lastname: Croxatto
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D008183:Luteal Phase / Q000187:drug effects / Q000235:genetics; D008597:Menstrual Cycle / Q000187:drug effects / Q000235:genetics*; D015735:Mifepristone / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010060:Ovulation / Q000187:drug effects / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D006727:Hormone Antagonists; D015735:Mifepristone