The origin and possible mechanism of embryonic cell‑free DNA release in spent embryo culture media: a review

Handayani, Nining and Aubry, Daniel and Boediono, Arief and Wiweko, Budi and Sirait, Batara I. and Sini, Ivan and Polim, Arie A and Dwiranti, Astari and Bowolaksono, Anom (2023) The origin and possible mechanism of embryonic cell‑free DNA release in spent embryo culture media: a review. Journal of Assisted Reproduction and Genetics. pp. 1231-1242.

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Abstract

The presence of cell-free DNA in spent embryo culture media (SECM) has unveiled its possible utilization for embryonic ploidy determination, opening new frontiers for the development of a non-invasive pre-implantation genetic screening tech- nique. While a growing number of studies have shown a high concordance between genetic screening using cell-free DNA (cfDNA) and trophectoderm (TE), the mechanism pertaining to the release of cfDNA in SECM is largely unknown. This review aims to evaluate research evidence on the origin and possible mechanisms for the liberations of embryonic DNA in SECM, including findings on the self-correction abilities of embryos which might contribute to the presence of cfDNA. Several databases including EMBASE, PUBMED, and SCOPUS were used to retrieve original articles, reviews, and opinion papers. The keywords used for the search were related to the origins and release mechanism of cfDNA. cfDNA in SECM originates from embryonic cells and, at some levels, non-embryonic cells such as maternal DNA and exogenous foreign DNA. The apoptotic pathway has been demonstrated to eliminate aneuploid cells in developing mosaic embryos which might culminate to the release of cfDNA in SECM. Nonetheless, there is a recognized need for exploring other pathways such as cross-talk molecules called extracellular vesicles (EVs) made of small, round bi-layer membranes. During in vitro develop- ment, embryos physiologically and actively expel EVs containing not only protein and microRNA but also embryonic DNA, hence, potentially releasing cfDNA of embryonic origin into SECM through EVs. Keywords Apoptosis · Cell-free DNA · In vitro fertilization · Spent embryo culture media · niPGT-A

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