CALM2 GENE EXPRESSION LEVELS IN THE CUMULUS CELLS AS A MARKER FOR CHROMOSOMAL ABNORMALITIES IN THE EMBRYO IN IN VITRO FERTILIZATION PROGRAMS


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Abstract

Objective. To search for molecular genetic markers associated with chromosomal abnormalities in embryos in order to optimize the selection of transferred embryos to enhance the efficiency of infertility treatment using assisted reproductive technologies. Subjects and methods. 42 cumulus cell samples from 11 patients who had undergone an in vitro fertilization (IVF) (intracytoplasmic sperm injection, ICSI) + preimplantation genetic screening (PGS) program were analyzed during the conducted study. The obtained embryos were divided into 4 groups according to the presence of their chromosomal abnormalities: 1) embryos without chromosomal abnormalities (20 samples); 2) those with sex chromosomal aneuploidies (n = 3); 3) those with somatic chromosomal aneuploidies (n =15); 4) heteroploid embryos (n = 4). A real-time RT-PCR assay was used to examine the cumulus cell mRNA expression in 10genes: hyaluronan synthase 2 (HAS2), prostaglandin synthase 2 (PTFS2), gremlin 1 (GREM1), versican (VCAN), inositol-triphosphate 3 kinase A (ITPKA), activated leukocyte cell adhesion molecules (ALCAM or CD 166), syndecan 4 (SDC4), calmodulin 2 (CALM2), SPRY domain-containing suppressor of cytokine signaling box protein 2 (SPSB2), and tumor protein 5313 (TP5313). Results. There was a relationship between the mRNA expression level in the СD166 (ALCAM), SDC4, VCAN and CALM2 genes and the presence of chromosomal abnormalities of the embryo (p = 0.004, p = 0.009, p = 0.042, p = 0.054, respectively). Discriminant analysis showed that the mRNA expression level in the CALM2 gene is the most informative marker for chromosomal abnormalities in the embryos in IVF programs. The study revealed that the poor embryo quality group showed chromosomal abnormalities in 78.6% of cases (OR = 5.7 (1.4 to 23.9);p = 0.023). There were no statistically significant differences between the mRNA expression level in the studied genes and the quality of developing embryos (p > 0.05). Conclusion. The mRNA expression level in the CALM2 gene is the most informative marker for chromosomal abnormalities in the embryos in IVF programs. However, there is a need for further investigation of the gene expression profile to search for potential biomarkers in the cumulus cells in order to create a prognostic model that can highly accurately predict the probability of chromosomal abnormalities in the embryos. This mathematical model will be able to further optimize the selection of transferred embryos, thereby enhancing the effectiveness of IVF programs as a whole.

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About the authors

Natalia Aleksandrovna Safronova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: safronchik9090@bk.ru
M.D., postgraduate of the department of assisted reproductive technology in infertility treatment Moscow 117997, Ac. Oparina str. 4, Russia

Elena Anatolievna Kalinina

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: e_kalinina@oparina4.ru
M.D, Ph.D, The Head of the department of assisted reproductive technology in infertility treatment Moscow 117997, Ac. Oparina str. 4, Russia

Andrew Evgenievich Donnikov

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: a_donnikov@oparina4.ru
PhD, Senior Researcher of molecular-genetical laboratory Moscow 117997, Ac. Oparina str. 4, Russia

Olga Vladimirovna Bourmenskaya

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: o_bourmenskaya@oparina4.ru
Ph.D., Researcher of molecular-genetical laboratory Moscow 117997, Ac. Oparina str. 4, Russia

Natalia Petrovna Makarova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: np.makarova@gmail.com
PhD, Researcher of the department of assisted reproductive technology in infertility treatment Moscow 117997, Ac. Oparina str. 4, Russia

Vktoria Konstantinovna Gorshinova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: chiasma@mail.ru
M.D., postgraduate of the department of assisted reproductive technology in infertility treatment Moscow 117997, Ac. Oparina str. 4, Russia

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