Cell lines from morphologically abnormal discarded IVF embryos are typically euploid and unaccompanied by intrachromosomal aberrations
Summary
Routine IVF practices result in the discarding of a significant proportion of embryos due to their unsuitability for transfer or cryopreservation. The present study plated clinically unusable human blastocysts to derive cellular outgrowths for aneuploidy studies and genome-wide analysis of DNA copy number variations, and to evaluate their potential as a source for pluripotent stem cells. Just 79 cellular outgrowths were obtained from 1026 abnormal blastocysts (7.7%), reflecting their low developmental potential. Of these, 13 (16.5%) were karyotypically abnormal and included trisomies frequently detected in miscarriages, each of which was uniform (nonmosaic) and the result of meiotic nondisjunction. Evaluation of submicroscopic DNA gains and losses in 10 diploid cellular outgrowths did not identify increased rates of copy number variations. Five of these outgrowths were shown to express pluripotency markers and could be developed into cell lineages representative of the three germ layers. These data suggest that embryos with chromosomal abnormalities resist cell-line derivation, and mosaic aneuploidy produced from mitotic nondisjunction, common in preimplantation embryos, is likely to be diminished or lost under conditions of diploid cell competition. Furthermore, this work demonstrated that abnormal embryos discarded in IVF programmes can provide a valuable source for pluripotent stem cell lines. During IVF, a large proportion of embryos are clinically unsuitable due to abnormal development and these embryos only have a small chance of achieving a pregnancy. Here we used these abnormal embryos to create cell lines for genetic testing and to determine their potential as stem cells. Of the 1026 abnormal embryos used, 79 (7.7%) created cell lines, reflecting their low developmental potential. Of those, only 16.5% had chromosomal anomalies, a much lower number than expected. This included chromosome abnormalities frequently observed in miscarriages, all of which were found in each cell tested (nonmosaic) and originated from the egg or the sperm as opposed to cell division. In-depth testing of 10 normal cell lines for small DNA gains and losses did not reveal an increased frequency of mutations. Furthermore, five of the cell lines were examined for stem cell properties and found to exhibit the hallmark features of stem cells including their ability to make mature cells from different parts of the body. Our data suggest that embryos with abnormal chromosomes resist making cell lines and that abnormalities that arise during cell division are likely to be lost due to competition with normal cells. We also demonstrated that abnormal embryos usually discarded in IVF programmes can provide a valuable source for stem cell lines. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
| Authors | Bradley CK, Peura T, Dumevska B, Jovasevic A, Chami O, Schmidt U, Jansen RP, Stojanov T |
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| Journal | Reproductive biomedicine online |
| Publication Date | 2014 Jun;28(6):780-8 |
| PubMed | 24745836 |
| DOI | 10.1016/j.rbmo.2014.02.001 |