Proteomic profiling of human uterine extracellular vesicles reveal dynamic regulation of key players of embryo implantation and fertility during menstrual cycle

• DOI: 10.1002/pmic.202000211
• Publication Date: 2021-02-26T09:11:49Z
• Authors: Alin Rai; Qi Hui Poh; Monique Fatmous; Haoyun Fang; Shanti Gurung; Beverley Vollenhoven; Lois A. Salamonsen; David W. Greening
• Keywords: Proteome

Endometrial extracellular vesicles (EVs) are emerging as important players in reproductive biology. However, how their proteome is regulated throughout the menstrual cycle not known. Such information can provide novel insights into biological processes critical for embryo development, implantation, and successful pregnancy. Using mass spectrometry-based quantitative proteomics, we show that small EVs (sEVs) isolated from uterine lavage of fertile women (UL-sEV), compared to infertile women, laden with proteins implicated antioxidant activity (SOD1, GSTO1, MPO, CAT). Functionally, sEVs derived endometrial cells enhance function trophectoderm cells. Moreover, there was striking enrichment invasion-related (LGALS1/3, S100A4/11) UL-sEVs secretory (estrogen plus progesterone-driven, EP) versus proliferative (estrogen-driven, E) phase, several downregulated UL-sEVs. Consistent this, EP- E-primed epithelial promote invasion Interestingly, carry known players/predictors implantation (PRDX2, IDHC), receptivity (S100A4, FGB, SERPING1, CLU, ANXA2), success (CAT, YWHAE, PPIA), highlighting potential inform regarding status/pregnancy outcomes. Thus, this study provides reprograming soluble secretome fluid, hence fertility.