Poster Presentation 26th Annual Lorne Proteomics Symposium 2021

Proteomic profiling of human trophectoderm small extracellular vesicles reveal insights into implantation and remodeling through endometrial cell reprogramming (#80)

Qi Hui Poh 1 2 , Alin Rai 2 , Iska Carmichael 3 , Lois A Salamonsen 4 , David W Greening 1 2
  1. Biochemistry and Genetics, La Trobe University, Melbourne, Victoria, Australia
  2. Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
  3. Monash Micro Imaging, Monash University, Melbourne, VIC, Australia
  4. Hudson Institute of Medical Research, Melbourne, VIC, Australia

Embryo implantation into a receptive endometrium is a critical step in establishing pregnancy, with implantation failure accounting for up to two-thirds of unsuccessful pregnancies. This tightly regulated process requires reciprocal signalling between the blastocyst and endometrium, though factors regulating this crosstalk remain poorly understood. Maternally-derived factors, including endometrial extracellular vesicles (EVs), are known to signal to the embryo during implantation, however, the role of embryo-derived EVs remains largely unknown.  Here, we provide a comprehensive proteomic characterisation of a major class of EVs, termed small EVs (sEVs), released by cells from the outer layer of human embryos (trophectoderm). Highly purified sEVs obtained by density-gradient separation were characterised based on morphology, shape, size, and expression of classical sEV markers. A striking finding through proteomic dissection of sEVs was the enrichment of proteins involved in embryo development, immune regulation, and antioxidant activity; processes critical for successful implantation. We demonstrate that the sEVs are readily internalised by human endometrial cells, where they potentially upregulate expression of adhesion molecules in endometrial cells. Our findings provide critical molecular insights into trophectoderm sEV-mediated signalling to the endometrium during implantation.