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Review
. 2017 Jul 22;18(7):1578.
doi: 10.3390/ijms18071578.

Age-Related Loss of Cohesion: Causes and Effects

Jin-Mei Cheng  1   2 , Yi-Xun Liu  3
Affiliations
Review

Age-Related Loss of Cohesion: Causes and Effects

Jin-Mei Cheng et al. Int J Mol Sci. .

Abstract

Aneuploidy is a leading genetic cause of birth defects and lower implantation rates in humans. Most errors in chromosome number originate from oocytes. Aneuploidy in oocytes increases with advanced maternal age. Recent studies support the hypothesis that cohesion deterioration with advanced maternal age represents a leading cause of age-related aneuploidy. Cohesin generates cohesion, and is established only during the premeiotic S phase of fetal development without any replenishment throughout a female's period of fertility. Cohesion holds sister chromatids together until meiosis resumes at puberty, and then chromosome segregation requires the release of sister chromatid cohesion from chromosome arms and centromeres at anaphase I and anaphase II, respectively. The time of cohesion cleavage plays an important role in correct chromosome segregation. This review focuses specifically on the causes and effects of age-related cohesion deterioration in female meiosis.

Keywords: age; aneuploidy; cohesion; oocytes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic of cohesin structure in mice and humans. (A) The cohesin complex comprises four subunits, Smc1β, Smc3, Stag3 and Rec8, and surrounds sister chromatids in a ring-like protein structure in mice (B) and humans (C).
Figure 2
Figure 2
The cohesin-cleaving factors during maternal aging. (A) The correlation between spindle assembly checkpoint (SAC) and anaphase-promoting complex or cyclosome in association with Cdc20 (APC/Ccdc20) and cohesion. The active SAC causes APC/CCdc20 inactivation, which cannot degrade securin and cyclin B1 to cause the cleavage of cohesion structure and anaphase onset. Therefore, the SAC and APC/Ccdc20 indirectly regulate the cohesion structure (indicated by broken line). Full line T shows the inhibitive effects of two factors; (B) Premature activation of separase, Sgo2 degradation, and the increase of oxidative damage and intracellular pH may be the leading cause of cohesion-ring structure cleavage during maternal aging.
Figure 3
Figure 3
The effects of age-related cohesion loss. (A) An intact bivalent configuration is attached by an amphitelic microtubule bundle. The two sister chromatids of each homologous chromosome face towards the same spindle pole. The cohesion embraces the two sister chromatids at their centromeres and along the chromosome arm; (B) The chiasmata shift toward the distal chromosome with cohesion loss; (C) A bivalent configuration becomes two univalents at the time of chiasmata loss, which gives rise to arm cohesion deterioration; (D) Centromere cohesion loss can generate a single chromatid in oocytes. Centromere cohesion loss can cause an increase in sister inter-kinetochore distance, as well as the merotelic attachment of a sister kinetochore and the appearance of a single chromatid. Red circle, centromere; green line, microtubule.
See this image and copyright information in PMC

References

    1. Anifandis G., Markandona O., Dafopoulos K., Messini C., Tsezou A., Dimitraki M., Georgoulias P., Daponte A., Messinis I. Embryological Results of Couples Undergoing ICSI-ET Treatments with Males Carrying the Single Nucleotide Polymorphism rs175080 of the MLH3 Gene. Int. J. Mol. Sci. 2017;18:314. doi: 10.3390/ijms18020314. - DOI - PMC - PubMed
    1. Cheng J.M., Li J., Tang J.X., Cheng S.R., Deng S.L., Jin C., Zhang Y., Wang X.X., Zhou C.X., Liu Y.X. Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice. Cell Cycle. 2016;18:2454–2463. doi: 10.1080/15384101.2016.1201255. - DOI - PMC - PubMed
    1. Merriman J.A., Jennings P.C., McLaughlin E.A., Jones K.T. Effect of aging on superovulation efficiency, aneuploidy rates, and sister chromatid cohesion in mice aged up to 15 months. Biol. Reprod. 2011;49:1–6. - PubMed
    1. Camlin N.J., McLaughlin E.A., Holt J.E. The use of C57Bl/6 × CBA F1 hybrid cross as a model for human age-related oocyte aneuploidy. Mol. Reprod. Dev. 2017;84:6–7. - PubMed
    1. Fragouli E., Alfarawati S., Goodall N.N., Sanchez-Garcia J.F., Colls P., Wells D. The cytogenetics of polar bodies: Insights into female meiosis and the diagnosis of aneuploidy. Mol. Hum. Reprod. 2011;17:286–295. doi: 10.1093/molehr/gar024. - DOI - PubMed