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. 2019 Feb 16;8(2):163.
doi: 10.3390/cells8020163.

Direct Single-Cell Analysis of Human Polar Bodies and Cleavage-Stage Embryos Reveals No Evidence of the Telomere Theory of Reproductive Ageing in Relation to Aneuploidy Generation

Kara Turner  1 , Colleen Lynch  2 , Hannah Rouse  3 , Vimal Vasu  4   5 , Darren K Griffin  4
Affiliations

Direct Single-Cell Analysis of Human Polar Bodies and Cleavage-Stage Embryos Reveals No Evidence of the Telomere Theory of Reproductive Ageing in Relation to Aneuploidy Generation

Kara Turner et al. Cells. .

Abstract

Reproductive ageing in women, particularly after the age of 35, is associated with an exponential increase in the proportion of chromosomally abnormal oocytes produced. Several hypotheses have attempted to explain this observation, including the 'limited oocyte pool' hypothesis and the 'two-hit' hypothesis, the latter explaining that a depletion in oocyte quality with age results from the multiple opportune stages for errors to occur in meiosis. Recently however, the telomere theory of reproductive ageing in women has been proposed. This suggests that shortened telomeres in oocytes of women of advanced maternal age render oocytes unable to support fertilization and embryogenesis. Despite a credible rationale for the telomere theory of reproductive ageing in women, very few studies have assessed telomere length directly in human oocytes or preimplantation embryos. Therefore, we directly assessed relative telomere length in first polar bodies and blastomeres from cleavage stage (day 3) embryos. In both cell types we tested the hypothesis that (1) older women have shorter telomeres and (2) chromosomally abnormal (aneuploid) gametes/embryos have shorter telomeres. In all cases, we found no evidence of altered telomere length associated with age-related aneuploidy.

Keywords: aneuploidy; blastomeres; first polar bodies; reproductive ageing; telomere length.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Average relative telomere length of all first polar bodies from women aged 35 years old or under (n = 13) compared to women of advanced maternal age (n = 12). Results show that telomere length is slightly shorter in first polar bodies from women above 35 years old, however, this difference is not statistically significant (p = 0.35). The line on the lower end of the whisker represents the minimum T/S ratio, the bottom of the box represents the first quartile, the line through the middle region of the box represents the median T/S ratio, the top of the box represents the third quartile, and the line at the top of the whisker represents the maximum T/S ratio. Circles represent outliers between 1.5 and 3 box lengths from the upper region of the box. Asterisks represent extreme outliers that are more than 3 times the interquartile range from the third quartile.
Figure 2
Figure 2
Relative telomere lengths of aneuploid and euploid first polar bodies in relation to maternal age (n = 82 first polar bodies from n = 25 women). Results indicate no correlation between relative telomere length of first polar bodies and maternal age (p = 0.52).
Figure 3
Figure 3
Average relative telomere length in all blastomeres from younger women (n = 11) compared to those from women of advanced maternal age (n = 11). Relative telomere length is shorter in blastomeres derived from couples in which women were younger however this difference was not statistically significant (p = 1.0). The line on the lower end of the whisker represents the minimum T/S ratio, the bottom of the box represents the first quartile, the line through the middle region of the box represents the median T/S ratio, the top of the box represents the third quartile and the line at the top of the whisker represents the maximum T/S ratio. Circles represent outliers between 1.5 and 3 box lengths from the upper region of the box. Asterisks represent extreme outliers that are more than 3 times the interquartile range from the 3rd quartile.
Figure 4
Figure 4
Telomere length in blastomeres from cleavage stage embryos in relation to maternal age (n = 86 blastomeres from n = 22 couples). Results show no correlation (p = 0.14).
Figure 5
Figure 5
Relative telomere length of aneuploid first polar bodies (n = 12) in comparison to euploid first polar bodies (n = 12) assessed in all women. Results show no significant difference (p = 0.39). The line on the lower end of the whisker represents the minimum T/S ratio, the bottom of the box represents the first quartile, the line through the middle region of the box represents the median T/S ratio, the top of the box represents the third quartile, and the line at the top of the whisker represents the maximum T/S ratio. Circles represent outliers between 1.5 and 3 box lengths from the upper region of the box. Asterisks represent extreme outliers that are more than three times the interquartile range from the third quartile.
Figure 6
Figure 6
Relative telomere length of euploid first polar bodies in women aged 35 years or younger (n = 11) in comparison to woman over the age of 35 (n = 11). Results show no significant difference between the groups (p = 0.16). The line on the lower end of the whisker represents the minimum T/S ratio, the bottom of the box represents the first quartile, the line through the middle region of the box represents the median T/S ratio, the top of the box represents the third quartile, and the line at the top of the whisker represents the maximum T/S ratio. Circles represent outliers between 1.5 and 3 box lengths from the upper region of the box. Asterisks represent extreme outliers that are more than three times the interquartile range from the 3rd quartile.
Figure 7
Figure 7
Relative telomere length of aneuploid first polar bodies in women aged 35 years or younger (n = 8) in comparison to woman over the age of 35 (n = 12). Results show no significant difference between the groups (p = 0.89). The line on the lower end of the whisker represents the minimum T/S ratio, the bottom of the box represents the first quartile, the line through the middle region of the box represents the median T/S ratio, the top of the box represents the third quartile and the line at the top of the whisker represents the maximum T/S ratio. Circles represent outliers between 1.5 and 3 box lengths from the upper region of the box. Asterisks represent extreme outliers that are more than three times the interquartile range from the third quartile.
Figure 8
Figure 8
Relative telomere length of euploid (n = 21) and aneuploid (n = 21) blastomeres assessed from all couples. Results show no significant difference (p = 1.0). The line on the lower end of the whisker represents the minimum T/S ratio, the bottom of the box represents the first quartile, the line through the middle region of the box represents the median T/S ratio, the top of the box represents the third quartile and the line at the top of the whisker represents the maximum T/S ratio. Circles represent outliers between 1.5 and 3 box lengths from the upper region of the box. Asterisks represent extreme outliers that are more than three times the interquartile range from the third quartile.
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