The Effect of Ethylmethylhydroxypyridine Succinate (Mexidol) on Oocyte Meiotic Maturation, Genome Integrity, and the Change in Gene Expression in Mouse Cumulus Cells under the Conditions of Systemic Immune Complex Damage

Abstract

The effect of ethylmethylhydroxypyridine succinate (HS, Mexidol) on oocyte meiotic maturation, level of DNA damage in follicular cells, and gene expression of gremlin 1 (Grem1), hyaluronan synthase 2 (HAS2), and cyclooxygenase 2 (COX2) in cumulus cells has been investigated using a model of experimental systemic immune complex damage induced by long-term immunization of CBA mice with bovine serum albumin (BSA). According to the literature data, these genes play a critical role in oogenesis and can characterize oocyte quality. The administration of HS exhibited a protective effect on the morphological and functional state of ovarian cells. The introduction of HS attenuated the genotoxic stress induced by BSA, which was reflected in a decrease in the number of cumulus cells with severe DNA damage. The following changes in gene expression have been observed: a 1.61-fold increase in the number of COX2 mRNA and a 1.47-fold increase in Grem1 mRNA. A 1.38-fold increase in the content of HAS2 gene transcripts has also been demonstrated, although this change was not statistically significant. The observed changes had a positive effect on oocyte meiotic maturation and were accompanied by a significant increase in the oocyte number during metaphase I and II. It is proposed that HS can be successfully used in the therapy of immune complex diseases.

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Funding

This study was supported by the National Academy of Sciences of Ukraine.

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E.A. Kondratskaya, N.G. Grushka, and T.Yu. Voznesenskaya designed the experiments, analyzed and interpreted data, performed literature search, and cowrote the paper; R.I. Yanchii designed the experiments, performed interpretation of the data, and provided critical comments on the manuscript.

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Correspondence to E. A. Kondratskaya.

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Conflict of interest. The authors declare that they have no conflict of interest. All authors read and approved the final version of the manuscript.

Statement on the welfare of animals. All applicable international principles of European Convention for the Protection of Vertebrate Animals (Strasburg, 1986) were followed.

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Translated by I. Matiulko

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Kondratskaya, E.A., Grushka, N.G., Voznesenskaya, T.Y. et al. The Effect of Ethylmethylhydroxypyridine Succinate (Mexidol) on Oocyte Meiotic Maturation, Genome Integrity, and the Change in Gene Expression in Mouse Cumulus Cells under the Conditions of Systemic Immune Complex Damage. Russ J Dev Biol 51, 183–188 (2020). https://doi.org/10.1134/S1062360420030030

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Keywords:

  • BSA immunization
  • oocyte meiotic maturation
  • genome integrity
  • gene expression
  • cumulus cells