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Application of Minimally-invasive Uterine Fluid Aspiration to Identify Candidate Biomarkers of Endometrial Receptivity through a Transcriptomic Approach

The endometrium is receptive to the embryo during a restricted window in the mid-secretory phase. My objectives were to develop a minimally-invasive endometrial sampling method for gene expression profiling, and to identify genes differentially expressed in the receptive phase. Twenty-three normo-ovulatory women underwent uterine fluid aspiration during the pre-receptive (LH+2) and receptive (LH+7) phase of the same natural cycle. RNA was extracted, reverse transcribed, amplified and hybridized to whole-genome microarrays. Unsupervised hierarchical clustering revealed self-segregation of pre-receptive and receptive samples. Importantly, profiling by uterine fluid aspiration was representative of biopsy. An unpaired t-test with a false discovery rate of 0.05 and a Δ threshold of 4-fold identified 245 unique transcripts as differentially expressed in the receptive phase. NanoString analysis validated 96% of these genes. This approach will now allow us to correlate expression of these candidate biomarkers to implantation outcomes, towards the development of clinical assays predictive for endometrial receptivity.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/43986
Date17 March 2014
CreatorsChan, Crystal
ContributorsBrown, Theodore
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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