Telomere length in trophectoderm and inner cell mass of human blastocysts: comparative analysis and assessment of influencing factors

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Abstract

BACKGROUND: The study of telomere length and influencing factors in early human development has both fundamental and applied importance.

AIM: A comparative assessment of telomere length in the compartments of human blastocysts, and the analysis of the telomere length association with the quality of blastocysts, genetic imbalance and the maternal age.

MATERIALS AND METHODS: The study was performed on trophectoderm and inner cell mass samples of 41 human blastocysts, 26 of which were genetically imbalanced according to preimplantation genetic testing and verification of its results. The microscope slides were prepared for further telomere detection in interphase nuclei by quantitative fluorescence in situ hybridization (Q-FISH).

RESULTS: Telomeres in trophectoderm were longer than in inner cell mass, with their length varied from blastocyst to blastocyst. Telomere length in either trophectoderm or inner cell mass did not differ between genetically balanced and imbalanced blastocysts. There was a tendency towards a decrease in telomere length in the blastocyst compartments with increasing maternal age, however, a statistically significant correlation was not confirmed. The telomere length in the inner cell mass, but not in the trophectoderm, was associated with blasocysts’ quality based on the Gardner grade: medium quality blastocysts had longer telomeres than high quality blastocysts.

CONCLUSIONS: Long telomeres in trophectoderm may be necessary for implantation and subsequent placentation. Telomere length can be considered among modifiers of the effects of karyotype abnormalities and other negative factors: the inheritance by an embryo of long telomeres apparently gives it a developmental advantage even when genetically imbalanced or has poor morphology. Implantation seems to be an important checkpoint for negative selection of embryos with “unsuccessful” combinations of telomere length, karyotype, and morphology.

About the authors

Andrey V. Tikhonov

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Author for correspondence.
Email: tixonov5790@gmail.com
ORCID iD: 0000-0002-2557-6642
SPIN-code: 3170-2629

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Olga A. Efimova

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Email: efimova_o82@mail.ru
ORCID iD: 0000-0003-4495-0983
SPIN-code: 6959-5014

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Mikhail I. Krapivin

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Email: krapivin-mihail@mail.ru
ORCID iD: 0000-0002-1693-5973
SPIN-code: 4989-1932
Russian Federation, Saint Petersburg

Olga V. Malysheva

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Email: omal99@mail.ru
ORCID iD: 0000-0002-8626-5071
SPIN-code: 1740-2691

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Evgenia M. Komarova

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Email: evgmkomarova@gmail.com
ORCID iD: 0000-0002-9988-9879
SPIN-code: 1056-7821

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Arina V. Golubeva

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Email: AlikovaAV1504@yandex.ru
ORCID iD: 0000-0003-1613-222X
SPIN-code: 4610-3686
Russian Federation, Saint Petersburg

Anna A. Pendina

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Email: pendina@mail.ru
ORCID iD: 0000-0001-9182-9188
SPIN-code: 3123-2133

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

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Supplementary files

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2. Fig. 1. Interphase nuclei from trophectoderm (а) and inner cell mass (b) of a human blastocyst after telomere detection by Q-FISH using telomeric DNA probes (yellow) and staining with DAPI (blue)

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3. Fig. 2. Mean relative telomere lengths in trophectoderm and inner cell mass of 41 human blastocysts

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4. Fig. 3. The scatter plots of the mean relative telomere lengths in trophectoderm (ТЭ) (a) and in inner cell mass (ВКМ) (b) and maternal age. The Spearman test showed no significant correlations (ρ = –0.1118, p = 0.4866 for TE and ρ = –0.2768, p = 0.0798 for ICM)

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5. Fig. 4. The comparisons of mean relative telomere lengths between blastocysts of high and medium quality. Telomere lengths do not differ between trophectoderms (a). Telomeres in inner cell mass (b) are longer in medium quality blastocysts compared to telomeres of high quality blastocysts

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