eLife assessment: Vertical transmission of maternal DNA through extracellular vesicles associates with altered embryo bioenergetics during the periconception period
Year: 2023
Type: peer-review
Abstract: The transmission of DNA through extracellular vesicles (EVs) represents a novel genetic material transfer mechanism that may impact genome evolution and tumorigenesis.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 nuclearencoded (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. eLife assessmentThis manuscript reports important results on the potential influence of maternally derived extracellular vesicles on embryo metabolism.The study combines convincing techniques for isolating different subtypes of EV, DNA sequencing, embryo culture, and respiration assays performed on human endometrial samples and mouse embryos.These findings set the stage for in-depth studies
Author: Jun Wu
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Funder: Instituto de Salud Carlos III
Awards: Función del ADN y ARN contenido en vesículas extracelulares secretadas por el endometrio humano sobre el embrión pre-implantatorio., Caracterización transcriptómica de la implantación embrionaria humana a nivel de célula única usando un endometrio 3D en un chip de microfluidica., Estudio del impacto del microbioma endometrial sobre el endometrio humano en condiciones fisiológicas y patológicas a nivel de célula única.
OpenAlex ID: W4390267347