Dynamics of endometrial transcriptome alterations induced by trophoblast derived extracellular vesicles

One of the most critical steps in mammalian reproduction is Implantation. Embryos with impaired capacity for embryo-maternal cross talk are thought to have reduced potential for implantation. One agent of embryo-maternal communications are extracellular vesicles (EV). EVs are li-pid-bilayer bound biological nanoparticles implicated in intercellular communication between many of the known cell types. In the current study, we have isolated EVs from trophoblast analogue JAr spheroids and supplemented the EVs to receptive endometrium analogue RL95-2 cells to simulate pre-implantation embryo-maternal dialogue. The transcriptome of the endometrial cells was examined at 30-minutes, 4-hours and 48-hours intervals using nanopore technology. At the time points 30-minutes, 4-hours and 48-hours the endometrial cells showed a significantly altered transcriptome. It seems trophoblast EVs induce a swift and drastic effect on the endometrial transcriptome. The effect peaks at around 4-hours of EV supplementation, indicating a generalized effect on cell physiology. Alterations are especially apparent in biological pathways critical in embryo implantation such as extracellular matrix receptor interactions and cytokine receptor interactions. These observations can be helpful in elucidating the dynamics of embryo-maternal communication in the pre-implantation period.