About the research
In this study, we aimed to investigate the potential for vertical DNA transmission within maternal endometrial EVs to the pre-implantation embryo and describe any effect on embryo bioenergetics
We discovered that the human endometrium secretes all three general subtypes of EV – apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs) – into the human endometrial fluid (EF) within the uterine cavity. EVs become uniformly secreted into the EF during the menstrual cycle, with the proportion of different EV populations remaining constant; however, MVs contain significantly higher levels of mitochondrial (mt)DNA than ABs or EXOs. During the window of implantation, MVs contain an eleven-fold higher level of mtDNA when compared to cells-of-origin within the receptive endometrium, which possesses a lower mtDNA content and displays the upregulated expression of mitophagy-related genes. Furthermore, we demonstrate the internalization of EV-derived nuclear-encoded (n)DNA/mtDNA by trophoblast cells of murine embryos, which associates with a reduction in mitochondrial respiration and ATP production.
These findings suggest that the maternal endometrium suffers a reduction in mtDNA content during the preconceptional period, that nDNA/mtDNA become packaged into secreted EVs that the embryo uptakes, and that the transfer of DNA to the embryo within EVs occurs alongside the modulation of bioenergetics during implantation
David Bolumar, Javier Moncayo-Arlandi, Javier Gonzalez-Fernandez, Ana Ochando, Inmaculada Moreno, Ana Monteagudo-Sanchez, Carlos Marin, Antonio Diez, Paula Fabra, Miguel Ángel Checa, Juan José Espinos, David K. Gardner, Carlos Simon, Felipe Vilella (2023) Vertical transmission of maternal DNA through extracellular vesicles associates with altered embryo bioenergetics during the periconception periode. eLife 12:RP88008. https://doi.org/10.7554/eLife.88008.3