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Review
. 2022 Mar 7;23(5):2880.
doi: 10.3390/ijms23052880.

Chromosome Segregation in the Oocyte: What Goes Wrong during Aging

Affiliations
Review

Chromosome Segregation in the Oocyte: What Goes Wrong during Aging

Marta Wasielak-Politowska et al. Int J Mol Sci. .

Abstract

Human female fertility and reproductive lifespan decrease significantly with age, resulting in an extended post-reproductive period. The central dogma in human female reproduction contains two important aspects. One is the pool of oocytes in the human ovary (the ovarian reserve; approximately 106 at birth), which diminishes throughout life until menopause around the age of 50 (approximately 103 oocytes) in women. The second is the quality of oocytes, including the correctness of meiotic divisions, among other factors. Notably, the increased rate of sub- and infertility, aneuploidy, miscarriages, and birth defects are associated with advanced maternal age, especially in women above 35 years of age. This postponement is also relevant for human evolution; decades ago, the female aging-related fertility drop was not as important as it is today because women were having their children at a younger age. Spindle assembly is crucial for chromosome segregation during each cell division and oocyte maturation, making it an important event for euploidy. Consequently, aberrations in this segregation process, especially during the first meiotic division in human eggs, can lead to implantation failure or spontaneous abortion. Today, human reproductive medicine is also facing a high prevalence of aneuploidy, even in young females. However, the shift in the reproductive phase of humans and the strong increase in errors make the problem much more dramatic at later stages of the female reproductive phase. Aneuploidy in human eggs could be the result of the non-disjunction of entire chromosomes or sister chromatids during oocyte meiosis, but partial or segmental aneuploidies are also relevant. In this review, we intend to describe the relevance of the spindle apparatus during oocyte maturation for proper chromosome segregation in the context of maternal aging and the female reproductive lifespan.

Keywords: aneuploidy; chromosome segregation; euploidy; maternal aging; oocytes; spindle assembly; spindle formation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Scheme showing the processes of meiosis I and II of the human oocyte and the zygote formation after fertilization. (B) Scheme showing the physiological stages of prophase I (first meiotic division) in oocytes, which consists of the leptotene, zygotene, pachytene, diplotene, and diakinesis stages. (For better visualization, the spindles are shown larger than their physiological size compared with the size of the oocyte).
Figure 2
Figure 2
Positioning of the meiosis II spindle. At the end of meiosis I, the spindle and the cortical cap interact to generate mechanical forces that lead to the extrusion of the first polar body. The cortical actin-rich domain (actin cap) is formed through the chromosome-associated RAN-GTP-dependent signaling after spindle migration to the cortex during meiosis I. After the extrusion of the first polar body, meiosis II is initiated, which requires the assembly and active maintenance of the spindle near the actin cap through RAN-GTP-dependent chromatin signaling. As a consequence, the Arp2/3 complex is activated to induce actin filament nucleation and support retrograde actin flow along the lateral cortex and back toward the oocyte center. This cytoplasmic streaming in the direction of the actin cap pushes the spindle toward the cap domain. Microtubule nucleation is depicted in the left zoom-in box, showing the Augmin complex, which recruits γ-TuRCs at the surface of the “mother microtubule” to initiate nucleation of “branching microtubules”. The Augmin-dependent recruitment takes place in the presence of NEDD1 (for better visualization, the pushing forces are depicted with black arrows, and spindles are shown larger than their physiological size compared to the size of the oocyte).
Figure 3
Figure 3
Scheme showing well-known anomalies of the human karyotype. The trisomies of chromosomes 13, 18, and 21 are shown. Moreover, two common aneuploidies of the sex-chromosomes are shown. The procedure of preimplantation genetic testing for aneuploidy prior to human embryo transfer is available only in some countries because of ethical reasons.

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References

    1. Ely D.M., Hamilton B.E. Trends in Fertility and Mother’s Age at First Birth Among Rural and Metropolitan Counties: United States, 2007–2017. National Center for Health Statistics; Hyattsville, MD, USA: 2018. pp. 1–8. - PubMed
    1. Moghadam A.R.E., Moghadam M.T., Hemadi M., Saki G. Oocyte quality and aging. JBRA Assist. Reprod. 2022;26:105. doi: 10.5935/1518-0557.20210026. - DOI - PMC - PubMed
    1. Mason J.B., Habermehl T.L., Underwood K.B., Schneider A., Brieño-Enriquez M.A., Masternak M.M., Parkinson K.C. The Interrelationship Between Female Reproductive Aging and Survival. J. Gerontol. Ser. A. 2022;77:75–83. doi: 10.1093/gerona/glab252. - DOI - PMC - PubMed
    1. Babayev E., Duncan F.E. Age-associated changes in cumulus cells and follicular fluid: The local oocyte microenvironment as a determinant of gamete quality. Biol. Reprod. 2022;106:351–365. doi: 10.1093/biolre/ioab241. - DOI - PMC - PubMed
    1. Sauer M.V., Paulson R.J., Lobo R.A. A Preliminary Report on Oocyte Donation Extending Reproductive Potential to Women over 40. N. Engl. J. Med. 1990;323:1157–1160. doi: 10.1056/NEJM199010253231702. - DOI - PubMed

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