Trends in Cell Biology
ReviewSpecial Issue: Cell CycleMechanisms of Aneuploidy in Human Eggs
Section snippets
Aneuploidy in Human Oocytes: A Topic of Growing Relevance in Society
Over the past century, greater medical knowledge and technological advances have improved the quality and duration of human lives. By contrast, the span of female fertility remains unchanged. A limited reserve of oocytes (see Glossary) is formed before birth, but gradually declines in quality with age, resulting in reduced fertility and an age-related increase in eggs with an abnormal number of chromosomes, termed ‘aneuploidy’. Despite this concern, women more frequently delay having their
Meiosis in Human Oocytes
Meiosis involves two successive cell divisions, in which first homologous chromosomes (meiosis I) and then sister chromatids (meiosis II) separate. The segregation of homologous chromosomes during the first meiotic division requires that the homologous chromosomes become linked with each other. These links are established in the early stages of oocyte development during growth of the female fetus in a process called homologous recombination [3] (Figure 1). The maternal and paternal chromosomes
Types of Aneuploidy in Human Oocytes
Recent technological developments have increased the ability to detect aneuploidy in eggs or during the early stages of embryonic development (See Outstanding Questions). During preimplantation genetic diagnostics, cells of an embryo can sometimes be biopsied and screened for genetic abnormalities to select healthy embryos for implantation [21]. Testing of oocytes can be helpful and may minimize the need to test embryos. In particular, polar bodies can be used to determine the cytology of an
Age-Related Causes of Aneuploidy
Women experience a gradual loss in the ability to become pregnant as they become older. Infertility is often reached from the age of 35 to about 10 years later. Meiotic chromosome segregation errors increase sharply in this age window. A comprehensive cytogenetic analysis examining more than 20 000 human oocytes by FISH reported that aneuploidy occurs in 20% of oocytes from 35-year-old women and increases to nearly 60% of oocytes from women over 43 years of age [39]. Recent studies utilizing
Age-Independent Causes of Aneuploidy
Aneuploidy affects not only eggs from older women, but also those from younger women since eggs produced by young women in the prime years of reproductive potential are still frequently defective. Eggs donated by young women for IVF often produce embryos with aneuploidy 43, 71 and many individuals with Down's syndrome are born to mothers under the age of 35 72, 73. Depending on the study, 3–61% of oocytes from women younger than 30 years of age are affected by aneuploidy 74, 75, 76, suggesting
Concluding Remarks
Human oocytes frequently experience chromosome segregation errors in meiosis that result in aneuploidy. As women become older, their oocytes lose the potential to give rise to viable embryos. Several pathways contribute to errors in meiosis. Age-related changes to the structure of chromosomes in oocytes promote incorrect attachments of chromosomes to the meiotic spindle and the premature splitting of bivalents before cell division. What is the cause of these age-related structural changes? In
Acknowledgments
It was the authors’ intention to write an article accessible to a wide audience while also including as many new and exciting studies as possible. We would like to apologize for any omissions, because these were unintentional or due to space limitations imposed by the journal. We thank Agata Zielinska and other members of the Schuh lab for critical review of this article. M.S. and A.W. have received financial support from the Max Planck Society, the European Research Council under grant
Glossary
- Anaphase
- the stage of cell division when the spindle segregates chromosomes by pulling them to opposite spindle poles.
- Blastocyst
- a stage in early embryo development that forms before implantation into the uterus.
- Centromere
- the region of a chromosome where the kinetochore is assembled and microtubules attach.
- Homologous recombination
- an event specific to meiosis where DNA of homologous chromosomes is covalently exchanged to produce chromosomes with new allele combinations and that links homologous
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