China
Africa
Explore chapters and articles related to this topic
Mosaicism Mechanisms in Preimplantation Embryos
Published in Darren K. Griffin, Gary L. Harton, Preimplantation Genetic Testing, 2020
Maurizio Poli, Antonio Capalbo
Incidence of mosaicism in human fetuses was reported to be lower than 0.5% [29]. When CVS testing or amniocentesis were followed up, no differences were reported in incidence of mosaicism between natural and IVF pregnancies [29,30]. These results suggest that IVF-related procedures are not an independent risk factor for the occurrence of mosaicism in preimplantation embryos. However, this evidence is in sharp contrast with the high incidence reported from PGT-A studies. It has been hypothesized that in a mosaic embryo, chromosomally abnormal cells may be selectively depleted during development, leading to an organism composed of euploid cells only [31,32]. A euploid lineage selection process was demonstrated in a murine model by Bolton and colleagues [33]. However, similar mechanisms in human embryos are still to be demonstrated. In addition, since aneuploidy in murines is not as frequent as in humans, mitotic errors in chromosome segregation had to be induced with administration of an exogenous compound (e.g., reversine). It is a possibility that the internalization of this chemical had a lethal effect on the cell, which was then depleted from the developing embryo not because of an aneuploidy self-detection mechanism but rather due to the cytotoxic effect of the compound. In addition, reversine treatment was shown to induce complex chromosomal alterations [33], instead of single aneuploidies, which are more common in human blastocysts [34]. For this reason, it is possible that the presence of complex abnormalities would result in cell cycle arrest, thus depleting aneuploid cells from the embryo. Although some of the data published suggest no preferential allocation of abnormal cells in specific cell lineages in human mosaic embryos [35], at present, no evidence about the existence of a correction/depletion mechanism of aneuploid through developmental progression has been reported. It is well documented how every chromosome can be found in an abnormal copy number (including full haploid configuration) in embryos at the blastocyst stage [7]. A large set of aneuploidies are also compatible with sustained implantation [36]. These observations suggest that a depletive mechanism targeting aneuploid cells in mosaic embryos after embryo genome activation (EGA) cannot alone explain either the significant reduction in mosaicism diagnosis in blastocyst-stage embryos compared to cleavage stage ones or the extremely low incidence of mosaicism in miscarried products of conception (POC).
The γH2AX DSB marker may not be a suitable biodosimeter to measure the biological MRT valley dose
Published in International Journal of Radiation Biology, 2021
Jessica A. Ventura, Jacqueline F. Donoghue, Cameron J. Nowell, Leonie M. Cann, Liam R. J. Day, Lloyd M. L. Smyth, Helen B. Forrester, Peter A. W. Rogers, Jeffrey C. Crosbie
Mice were irradiated in Hutch 2B on the IMBL at the Australian Synchrotron, with six mice for each irradiation cohort. Six mice were used as sham-irradiated controls. Animals were anesthetised and placed into custom-designed perspex jigs with Velcro straps to immobilize them and ensure accurate radiation delivery (Supplementary Figure 1(a)). Approximately 2 cm (in height) of skin on the back of the anesthetised mouse was stretched and clipped with 2 alligator clips to create a skin flap, allowing irradiation of the skin only. We verified the radiation dose delivered to the targeted area by using EBT3 radiochromic film (Ashland Specialty Ingredients, USA), which was also secured with the alligator clips and placed at the front and back of the skin flaps to monitor the skin entrance and exit doses. Following irradiation, animals were treated with Reversine and left to recover. Sham-irradiated controls were anesthetised and placed in the irradiation jigs in the same way as the irradiated animals followed by recovery using Reversine.