Vertical transmission of maternal DNA through extracellular vesicles associates with altered embryo bioenergetics during the periconception period
Bolumar, David (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))
Moncayo-Arlandi, Javier (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))
Gonzalez-Fernandez, Javier (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))
Ochando Hernandez, Ana (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))
Moreno, Inmaculada (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))
Monteagudo-Sánchez, Ana (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))
Marin, Carlos (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))
Diez, Antonio (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))
Fabra, Paula (Clinica Fertty)
Checa, Miguel Angel (Universitat Pompeu Fabra)
Espinós, Juan José (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública)
Gardner, David K. (University of Melbourne)
Simon, Carlos (Universitat de València)
Vilella, Felipe (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))

Date:	2023
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 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.
Grants:	Instituto de Salud Carlos III PI18/00957 Instituto de Salud Carlos III PI21/00528 Instituto de Salud Carlos III PI21/00235 Ministerio de Educación, Cultura y Deporte FPU15/02248 Instituto de Salud Carlos III PI19/00159 Instituto de Salud Carlos III CPII18/00020
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	eLife, 2023 , ISSN 2050-084X

DOI: 10.7554/eLife.88008
PMID: 38149847

21 p, 6.3 MB

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