Examinando por Autor "Tapia-Pizarro, Alejandro"

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    Effect of single post-ovulatory administration of mifepristone (RU486) on transcript profile during the receptive period in human endometrium
    (BioScientifica Ltd., 2016-04) Cuevas, Catherina A.; Tapia-Pizarro, Alejandro; Salvatierra, Ana María; Munroe, David J.; Velasquez, Luis; Croxatto, Horacio B.
    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 (LHC2, LHC0ZLH peak), and to determine the relationship of these transcripts with those regulated during the acquisition of receptivity. Endometrial samples were obtained in LHC7 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 LHC2 and LHC7 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 R2.0-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 (LHC2 vs LHC7). Approximately 2000 transcripts were significantly regulated in both comparisons (mifepristone vs placebo and LHC2 vs LHC7), 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 LHC2 to LHC7 seem to be regulated by the progesterone receptor and w37% of the genes whose transcript levels changed by effect of mifepristone could be associated with the acquisition of receptivity. Reproduction (2016) 151 331–349
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    Endometrial gene expression reveals compromised progesterone signaling in women refractory to embryo implantation
    (BioMed Central Ltd., 2014-09) Tapia-Pizarro, Alejandro; Figueroa, Paula; Brito, Julio; Marín, Juan C.; Munroe, David J.; Croxatto, Horacio B.
    Background: Endometrial function is essential for embryo implantation. The aim of this study was to analyze gene expression profiles from individual endometrial samples obtained from women with repeated implantation failure after IVF in oocyte donation programs. Methods: Seventeen volunteers were recruited: women who had previously participated as recipients in oocyte donation cycles and repeatedly exhibited implantation failure (Group A, study group, n = 5) or had at least one successful cycle (Group B, control group, n = 6) and spontaneously fertile women (Group C, normal fertility group, n = 6). An endometrial cycle was induced with exogenous estradiol (E2) and progesterone (P) and an endometrial sample was collected on the seventh day of P treatment. Results: Transcriptome analysis showed 82 genes with consistent differential gene expression when comparing A vs. B and A vs. C. One hundred transcripts differentially expressed in group A vs. B have been shown to be regulated by P, suggesting compromised P signaling in the endometrium. The P receptor (PR) mutation PROGINS was not detected in women from group A. Semi-quantitation of immunoreactive PRA/B, PRB and Sp1 (a transcription factor related to P signaling) in paraffin-embedded endometrial sections, did not show statistically significant differences amongst groups. However immunostaining glycodelin was significantly decreased in endometrial samples from group A Conclusions: We conclude that some cases of repeated implantation failure could be associated with an aberrant gene expression profile. Compromised P signaling might be the underlying mechanism for such endometrial gene expression deregulation in women with repeated implantation failure.