Increased somatic polyploidization in chorion of arrested pregnancies conceived through assisted reproductive technologies

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Abstract

BACKGROUND: The search for markers of disorders leading to miscarriage with normal embryonic karyotype is an important clinical and diagnostic problem, especially in pregnancies conceived with assisted reproductive technologies.

AIM: Analysis of chorionic cells ploidy in naturally and assisted reproductive technologies conceived pregnancies.

MATERIALS AND METHODS: A total of 52 chorion samples were included in the study. The samples were divided into groups depending on the developmental status of pregnancy (progressing/arrested), the way of conception (natural/assisted reproductive technologies) and karyotype (normal/trisomy 16). The ploidy of chorionic cells was studied using fluorescence in situ hybridization on interphase nuclei preparations. A total of 50,657 interphase nuclei were analyzed.

RESULTS: Along with predominant diploid cells, polyploid cells were detected in all chorionic samples. Their frequency varied among samples from 0.1 to 8.22%. Polyploid cells comprised mainly tetraploid cells which were detected in all samples; triploid cells were also detected in 45 samples, and octoploid cells — in 5 samples. The highest total frequency of all polyploid cell types was found in chorion from assisted reproductive technologies-conceived arrested pregnancies, and the lowest — in chorion from progressing pregnancies. Frequency of tetraploid cells demonstrated the same pattern. Frequency of triploid cells was not associated with a developmental status of pregnancy and the way of conception. However, in chorion samples with trisomy on chromosome 16 in naturally conceived arrested pregnancies, a tendency towards a decrease in the frequency of triploid cells was noted.

CONCLUSIONS: An elevated frequency of polyploid cells in chorion may indicate placentation abnormalities, leading to miscarriage even in the absence of embryonic karyotype anomalies. Therefore, an increase in somatic polyploidization in chorion may be considered a promising diagnostic marker of disorders in the placenta formation and functioning.

About the authors

Andrei V. Tikhonov

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

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

Cand. Sci. (Biology), Research Associate

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Mikhail I. Krapivin

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

Email: krapivin-mihail@mail.ru
ORCID iD: 0000-0002-1693-5973
SPIN-code: 4989-1932

Junior Research Associate

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Lyubov I. Petrova

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

Email: petrovaluba@mail.ru
ORCID iD: 0000-0002-2471-0256
SPIN-code: 8599-6886

Research Assistant

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Olga G. Chiryaeva

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

Email: chiryaeva@mail.ru
ORCID iD: 0000-0003-4441-1736
SPIN-code: 4027-4908

Cand. Sci. (Biology), biologist

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Elizaveta P. Pashkova

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

Email: lipashkova07@gmail.com
ORCID iD: 0000-0002-3035-522X

Nurse

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Arina V. Golubeva

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

Email: AlikovaAV1504@yandex.ru
ORCID iD: 0000-0003-1613-222X
SPIN-code: 4610-3686

Research Assistant

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Dmitrii A. Staroverov

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

Email: enigstaroverov@yandex.ru
ORCID iD: 0009-0004-9716-4964

Research Assistant

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Ekaterina D. Trusova

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

Email: trusova.ek@mail.ru
ORCID iD: 0009-0005-6529-5799

Research Assistant

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Olga A. Efimova

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

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

Cand. Sci. (Biology), Head of the Laboratory of Cytogenetics and Cytogenomics of Reproduction

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Olesya N. Bespalova

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

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN-code: 4732-8089

MD, Dr. Sci. (Medicine), Deputy Director for Research

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

Anna A. Pendina

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

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

Cand. Sci. (Biology), Senior Research Associate

Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034

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Supplementary files

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2. Fig. 1. Groups of chorionic villi samples formed according to the developmental status of pregnancy, the way of conception and karyotype. ART, assisted reproductive technologies

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3. Fig. 2. Diploid and tetraploid interphase nuclei from chorionic villi cells after fluorescence in situ hybridization with DNA probes specific to chromosome 13 (13q14, green) and chromosome 21 (21q22, red) and staining with DAPI (blue)

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4. Fig. 3. Frequency of tetraploid cells in 4 groups of chorionic villi samples, formed according to the developmental status of pregnancy, the way of conception and karyotype: 1, arrested pregnancy, conceived with assisted reproductive technologies, normal karyotype in chorion; 2, arrested pregnancy, natural conception, normal karyotype in chorion; 3, arrested pregnancy, natural conception, trisomy 16 in chorion; 4, progressing pregnancy, natural conception, normal karyotype in chorion

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5. Fig. 4. Frequency of triploid cells in 4 groups of chorionic villi samples, formed according to the developmental status of pregnancy, the way of conception and karyotype: 1, arrested pregnancy, conceived with assisted reproductive technologies, normal karyotype in chorion; 2, arrested pregnancy, natural conception, normal karyotype in chorion; 3, arrested pregnancy, natural conception, trisomy 16 in chorion; 4, progressing pregnancy, natural conception, normal karyotype in chorion

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6. Fig. 5. Ratios of triploid (3n), tetraploid (4n) and octoploid (8n) cells in 4 groups of chorionic villi samples, formed according to the developmental status of pregnancy, the way of conception and karyotype: 1, arrested pregnancy, conceived with assisted reproductive technologies, normal karyotype in chorion; 2, arrested pregnancy, natural conception, normal karyotype in chorion; 3, arrested pregnancy, natural conception, trisomy 16 in chorion; 4, progressing pregnancy, natural conception, normal karyotype in chorion

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