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Peering into the window of receptivity: extracellular vesicles containing small noncoding RNAs as potential biomarkers

      The window of receptivity is a specific time period during which the endometrium is appropriately prepared for embryonic implantation, which is surrounded by periods of a refractory endometrial status. The success of in vitro fertilization (IVF) is dependent on correctly timing an embryo transfer during maximal receptivity. Extensive research has been focused on examining the changes in genomics, transcriptomics, proteomics, and metabolomics in order to identify markers of the window of receptivity. Extracellular vesicles (EVs) have emerged as promising molecular biomarkers for receptivity. Extracellular vesicles are molecules secreted by cells that facilitate communication with other cells by activating signaling pathways. They are composed of small biomolecules surrounded by a phospholipid bilayer derived from the cell of origin. Extracellular vesicles have been identified and studied in many reproductive tissues including follicular fluid, semen, spent IVF culture media, uterine fluid, and the placenta. Animal data suggested that EVs were differentially expressed in the prereceptive vs. receptive endometrium (
      • Kusama K.
      • Nakamura K.
      • Bai R.
      • Nagaoka K.
      • Sakurai T.
      • Imakawa K.
      Intrauterine exosomes are required for bovine conceptus implantation.
      ). In a recent publication by Li et al. (
      • Li T.
      • Greenblatt E.M.
      • Shin M.E.
      • Brown T.J.
      • Chan C.
      Cargo small non-coding RNAs of extracellular vesicles isolated from the uterine fluid associate with endometrial receptivity and implantation success.
      ), small noncoding ribonucleic acids (sncRNAs) of EVs were isolated from the uterine fluid. Similar to the animal studies, the investigators sought to identify the EVs that may be associated with endometrial receptivity and subsequent implantation success.
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