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Moncayo-Arlandi, J.

Publications and source records attributed to Moncayo-Arlandi, J..

2 recordsLinked to original sources

Modeling human embryo adhesion using a microfluidic platform

Embryo adhesion represents the first step of implantation, yet understanding this process has been hindered by the lack of human in vitro platforms that replicate endometrial physiology. Here, we present a dual-channel microfluidic platform containing organoid-derived endometrial epithelium and primary stromal cells. Our model recapitulates important endometrial hallmarks including epithelial polarization, stromal decidualization, extracellular vesicle release, and hormone-induced receptivity. We tested its function by introducing mouse and human blastocysts and showed that embryos displayed features of initial adhesion. These included establishment of embryo-epithelial contacts initiated via the polar trophectoderm, inner cell mass repositioning, and lineage segregation. Moreover, human embryos secreted {beta}hCG indicating a functional trophoblast. Thus, this work provides a platform to study key features of embryo adhesion and endometrial receptivity, and disorders affecting embryo-endometrium interactions. TeaserEndometrium-on-a-chip shows detailed human embryo adhesion dynamics.

molecular biology↗

Vertical transmission of maternal mitochondrial DNA through extracellular vesicles modulates embryo bioenergetics

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.

developmental biology↗