Human Embryonic Aneuploidy


Human embryonic aneuploidy can have a meiotic or a mitotic origin. The majority of meiotic chromosome errors arise during oogenesis. Two main aneuploidy‐causing mechanisms have been defined: the first involves the nondisjunction of entire chromosomes and takes place during both meiotic divisions, whereas the second involves the premature division of a chromosome into its two sister chromatids during meiosis I, followed by their random segregation. Mitotic aneuploidy can arise as a consequence of problems such as nondisjunction, endoreduplication and anaphase lag and occurs most often during the first three divisions after fertilisation. The cleavage stage of development is characterised by the highest rates of aneuploidy, after which the incidence of cytogenetic abnormality decreases significantly. A large number of oocytes and embryos have been examined in order to define the spectrum of aneuploidies during the first few days of life and to shed light upon their origins. Various classical and molecular cytogenetic methods have been employed for this purpose, and valuable data of biological and clinical relevance have been obtained.

Key Concepts:

  • Aneuploidy is the most important genetic cause of human reproductive wastage (i.e. the principal reason for embryo implantation failure and miscarriage).

  • The outcome of assisted reproductive treatments (e.g. in vitro fertilisation (IVF)) and natural reproductive cycles is negatively affected by aneuploidy.

  • Most meiotically derived abnormalities arise during oogenesis.

  • There is a strong relationship between advancing female age and increasing aneuploidy rates in oocytes.

  • Two distinct mechanisms of oocyte chromosome malsegregation have been described, whole chromosome nondisjunction and unbalanced chromatid predivision.

  • Post‐zygotic aneuploidy usually arises during the first few mitotic divisions and leads to mosaicism in the embryo.

  • There are three main mechanisms responsible for aneuploidy of mitotic origin: anaphase lag, endoreduplication and mitotic nondisjunction.

  • The cleavage stage of preimplantation development is associated with the highest aneuploidy rates.

  • The frequency of chromosome abnormalities and mosaicism declines as embryos progress to the blastocyst stage, presumably due to loss of abnormal cells or demise of affected embryos.

Keywords: oocyte; preimplantation embryo; chromosome; aneuploidy; mosaicism

Figure 1.

aCGH profiles resulting from the analysis of a pair of first and second PBs are shown in (a) and (b), respectively. aCGH analysis of the first PB identified a gain of chromatid 15 (23,X,+15cht), whereas the 2nd PB was missing chromosomes 9 and 15 (21,X,‐9,‐15). The aCGH profile resulting from the analysis of a blastomere biopsied from a cleavage stage embryo is shown in (c). Multiple abnormalities were identified, including gains of chromosomes 1, 4, 5, 7, 9, 11, 14 and 18, and losses of chromosomes 3, 15, 19 and 22. The aCGH profile resulting from the analysis of a TE sample biopsied from a blastocyst stage embryo is shown in (d). A loss of chromosome 11 was detected in this TE sample.



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Fragouli, Elpida, and Wells, Dagan(Aug 2014) Human Embryonic Aneuploidy. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0025706]