P-420 Dysregulated microRNAs in uterine fluid from women with recurrent implantation failure are linked to endometrial receptivity and implantation
Autor: | C Von Grothusen, C Frisendahl, M Vijayachitra, L Parameswaran Grace, M Peters, O Faridani, S Andres, N Rao Boggavarapu, K Gemzell-Danielsson |
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Rok vydání: | 2022 |
Předmět: | |
Zdroj: | Human Reproduction. 37 |
ISSN: | 1460-2350 0268-1161 |
DOI: | 10.1093/humrep/deac107.397 |
Popis: | Study question Is the microRNA content different in uterine fluid (UF) from women with recurrent implantation failure (RIF) compared to healthy fertile women? Summary answer The miRNA content is altered in the UF of women with RIF compared to healthy fertile women. What is known already Previous studies indicate that microRNAs secreted from endometrial cells into the UF are involved in endometrial receptivity and embryo implantation. Moreover, endometrial miRNAs are dysregulated in women with RIF and poor endometrial receptivity has been suggested as a putative cause of the condition. Study design, size, duration This is a descriptive experimental case-control study where microRNA abundancy in UF was compared between women with RIF (n = 34) and healthy fertile women (n = 17). Study participants were recruited at two university clinics in Stockholm, Sweden, and Tartu, Estonia. UF samples were collected vaginally in the receptive phase on day LH + 7-9 by flushing the uterine cavity with sterile saline. RIF was defined as three failed in vitro fertilization (IVF) cycles with good-quality embryos. Participants/materials, setting, methods To identify miRNAs in UF we performed small RNA sequencing. Differential expression analysis (DESeq2) was used to compare the abundancy of miRNAs in UF between the two groups. Dysregulated miRNAs were externally validated using relevant published datasets and further analyzed using tools such as target gene prediction (miRTarBase) and biological KEGG pathway analysis (g:Profiler). Technical validation was performed on two miRNAs with quantitative real-time PCR (RT-PCR). Main results and the role of chance In total, we identified 61 differentially abundant UF microRNAs with a false discovery rate of Limitations, reasons for caution The sample size of this descriptive study was limited. A larger study cohort should be used to validate the differentially abundant microRNAs. Moreover, further in-vitro and in-vivo studies are needed to establish the role of identified miRNAs and their predicted target genes and enriched pathways in the pathogenesis of RIF. Wider implications of the findings RIF represents a true challenge in the IVF clinic. We show that total miRNAs can be comprehensively mapped in UF and constitute a promising source of non-invasive biomarkers for RIF that could be further evaluated for its clinical utility. Our findings also give insight into the molecular mechanisms of RIF. Trial registration number Not applicable |
Databáze: | OpenAIRE |
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