PhD Scientific Days 2024

Molecular Medicine I.

Changes in the MiRNA Cargo of EV-Mediated Fetal-Maternal Communication Following Light Treatment

Text of the abstract

Introduction: Light exposure of embryos during assisted reproduction affects embryo quality and implantation capacity in a wavelength dependent manner. We investigated the molecular mechanism of these light-induced changes through the comparative analysis of gene expression and regulatory miRNA profile of murine embryos cultured in dark environment and those exposed to white- or red filtered light.
Aims: After our initial findings, how light exposure of different wavelengths modify the implantation capacity of embryos and what changes occur in the mRNA and miRNA transcriptome of them, our group wanted to examine the effects on the miRNA content of the embryo-derived extracellular vesicles.
Methods: In vitro cultured mouse embryos (3.5 dpc) were exposed to white or red filtered light. After 24 hours the miRNA content of embryo-derived extracellular vesicles were isolated and RNA-sequencing was performed. Differential expression analysis and functional enrichment analysis were used for evaluating the transcriptome results.
Results: Embryo-derived extracellular vesicles enclosed wavelength dependently unique miRNA cargos the target genes of which play a role in embryo implantation. We have found many significantly changed miRNA within the embryo-derived extracellular vesicles, independent from the embrionic miRNA. Within the white light treated group miRNA targeting genes in cell signaling and extracellular matrix reorganization were downregulated. Meanwhile following the treatment with filtered red light, there were significant elevations in levels of miRNA, targeting genes, that play a role in the implantation of embyros. Furthermore there was significant changes in miRNA targeting immunological signaling pathways, namely Fc gamma signaling, DAP12 signaling and inflammatory signalization.
Conclusion: Extracellular vesicles of light exposed embryos play a role in blastocyst-decidua communication through the horizontal transfer of regulatory miRNAs. Our previous data prove that light exposure during in vitro fertilization modifies cell function that might affect the outcome of implantation. This current study shows that light exposure of embryos with different wavelengths, modify even the miRNA cargo of embryo-derived extracellular vesicles and influence the fetal-maternal crosstalk.
Funding: This work was supported by OTKA K 147483, TKP-EGA10 and STIA-KF-17.