Paper 1 by Velasquez Cumplido

About: Differences in the endometrial transcript profile during the receptive period between women who were refractory to implantation and those who achieved pregnancy.

Gene expression profiling of normal receptive endometrium has been characterized, but intrinsic defects in endometrial gene expression associated with implantation failure have not been reported. METHODS: Women who had previously participated as recipients in oocyte donation cycles and repeatedly exhibited implantation failure (Group A, study group) or had at least one successful cycle (Group B, control group) and spontaneously fertile women (Group C, normal fertility group) were recruited. All were treated with exogenous estradiol and progesterone to induce an endometrial cycle, and an endometrial biopsy was taken on the seventh day of progesterone adminis- tration. RNA from each sample was analysed by cDNA microarrays to identify differentially expressed genes between groups. RESULTS: 63 transcripts were differentially expressed (􏰀2-fold) between Groups A and B, of which 16 were subjected to real time RT–PCR. Eleven of these were significantly decreased in Group A with regard to Groups B and C. Among the dysregulated genes were MMP-7, CXCR4, PAEP and C4BPA. CONCLUSIONS: Repeated implantation failure in some oocyte recipients is associated with an intrinsic defect in the expression of multiple genes in their endometrium. Significantly decreased levels of several transcripts in endome- tria without manifest abnormalities is demonstrated for the first time and shown to be associated with implantation failure.

Funding


Funding for this work was provided by CONRAD (CIG-02-83 to L.V.); CONICYT (Beca Apoyo para realizacio ́n de Tesis Doctoral 2002 to A.T.); Beca Fulbright-CONICYT (to A.T.); DICYT (to L.V.) and with Federal Funds from the National Cancer Institute, National Institutes of Health, under contract no. N01-CO-12400 (Article H.36 of the Prime Contract). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Ser- vices, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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