THE INFLUENCE OF CHRONIC HYPOXIA ON THE PRENATAL DEVELOPMENT OF THE CONTRACTILE APPARATUS OF RAT CARDIOMYOCYTES

Tverdokhlib I. V., Kobeza P. A.

THE INFLUENCE OF CHRONIC HYPOXIA ON THE PRENATAL DEVELOPMENT OF THE CONTRACTILE APPARATUS OF RAT CARDIOMYOCYTES


Show/Download

About the author:

Tverdokhlib I. V., Kobeza P. A.

Heading:

MORPHOLOGY

Type of article:

Scientific article

Annotation:

There is a wide range of publications that analyze various aspects of the influence of prenatal hypoxia on ontogenetic transformations of the myocardium, however, the topological features of changes in the contractile apparatus of a cardiomyocyte that is formed and develops under conditions of chronic prenatal hypoxia require detailed study. The aim is establish the ultrastructural features of changes in the contractile apparatus of typical cardiomyocytes of different parts of the embryonic myocardium of rats under conditions of chronic hypoxia. The object of the study were the hearts of rat embryos obtained after the administration of sodium nitrite to pregnant females at a dose of 50 mg/kg daily from the 10th to the 20th day of gestation. The material was analyzed by transmission electron microscopy in 12 topographical localizations of the myocardium. Results. It has been established that hypoxia inhibits the formation of sarcomeres, leads to disorganization of myofibrils and mitochondrial damage. Starting from the 17th day of development, progressive destruction of contractile structures is observed: fragmentation of myofibrils, disruption of intercalated discs and disintegration of filaments. The greatest changes were recorded in the intramural and subendocardial zones of the ventricles. In the atria, hypoxia caused a restriction of the spatial organization of myofibrils without their pronounced lysis. Chronic prenatal hypoxia leads to inhibition of sarcomerogenesis and disorientation of myofibrils against the background of crystallolysis and swelling of mitochondria of typical cardiomyocytes mainly in the subendocardial zone of both ventricles and the interventricular septum. Starting from the 17th day of prenatal ontogenesis, the effect of chronic hypoxia is accompanied by fragmentation of newly formed myofibrils, dissociation of sarcomeres, splitting of telophragms and intercalated discs in the intramural and subepicardial zones of both ventricles.

Tags:

cardiomyocytes, chronic prenatal hypoxia, electron microscopy, myofibrillogenesis, rats

Bibliography:

  1. Belaidi E, Khouri C, Harki O, Baillieul S, Faury G, Briançon-Marjollet A, et al. Cardiac consequences of intermittent hypoxia: a matter of dose? A systematic review and meta-analysis in rodents. Eur Respir Rev. 2022;31(164):1-18. DOI: 10.1183/16000617.0269-2021.
  2. Bourdier G, Détrait M, Bouyon S, Lemarié E, Brasseur S, Doutreleau S, et al. Intermittent Hypoxia Triggers Early Cardiac Remodeling and Contractile Dysfunction in the Time-Course of Ischemic Cardiomyopathy in Rats. J Am Heart Assoc. 2020;9(16):14. DOI: 10.1161/JAHA.120.016369.
  3. Chen XY, Wang JQ, Cheng SJ, Wang Y, Deng MY, Yu T, et al. Diazoxide Post-conditioning Activates the HIF-1/HRE Pathway to induce myocardial protection in hypoxic/reoxygenated cardiomyocytes. Front Cardiovasc Med. 2021;8:1-13. DOI: 10.3389/fcvm.2021.711465.
  4. Harki O, Boete Q, Pépin JL, Arnaud C, Belaidi E, Faury G, et al. Intermittent hypoxia-related alterations in vascular structure and function: a systematic review and meta-analysis of rodent data. Eur Respir J. 2022;59(3):1-13. DOI: 10.1183/13993003.00866-2021.
  5. Hu K, Deng W, Yang J, Wei Y, Wen C, Li X, et al. Intermittent hypoxia reduces infarct size in rats with acute myocardial infarction: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2020;20(1)422:1-12. DOI: 10.1186/s12872-020-01702-y.
  6. Smith KLM, Swiderska A, Lock MC, Graham L, Iswari W, Choudhary T, et al. Chronic developmental hypoxia alters mitochondrial oxidative capacity and reactive oxygen species production in the fetal rat heart in a sex-dependent manner. J Pineal Res. 2022;73(3):e12821.1-16. DOI: 10.1111/jpi.12821.
  7. Jonker SS, Giraud GD, Espinoza HM, Davis EN, Crossley DA 2nd. Effects of chronic hypoxia on cardiac function measured by pressure- volume catheter in fetal chickens. Am J Physiol Regul Integr Comp Physiol. 2015;308(8):680-689. DOI: 10.1152/ajpregu.00484.2014.
  8. Kang PM, Haunstetter A, Aoki H, Usheva A, Izumo S. Morphological and molecular characterization of adult cardiomyocyte apoptosis during hypoxia and reoxygenation. Circ Res. 2000;87(2):118-125. DOI: 10.1161/01.res.87.2.118.
  9. Shati AA, Zaki MSA, Alqahtani YA, Haidara MA, Alshehri MA, Dawood AF, et al. Intermittent Short-Duration Re-oxygenation Attenuates Cardiac Changes in Response to Hypoxia: Histological, Ultrastructural and Oxidant/Antioxidant Parameters. Br J Biomed Sci. 2022;79:10150. DOI: 10.3389/bjbs.2022.10150.
  10. Sun Y, Jiang C, Hong H, Liu J, Qiu L, Huang Y, et al. Effects of hypoxia on cardiomyocyte proliferation and association with stage of development. Biomed Pharmacother. 2019;118:109391. DOI: 10.1016/j.biopha.2019.109391.
  11. Waleczek FJG, Cipriano G, Haas JA, Garg A, Pfanne A, Just A, et al. Prolonged Hypoxia in Rat Living Myocardial Slices Affects Function, Expression, and Structure. Int J Mol Sci. 2024;26(1):218. DOI: 10.3390/ijms26010218.
  12. Duka TI, Chorna VI. Vplyv hemichnoi hipoksii na dynamiku kontsentratsii GFKB u strukturakh mozku ta syrovattsi krovi shchuriv. Visnyk Dnipropetrovsk Univ Ser Biol Ekol. 2016;24(1):143-50. DOI: 10.15421/011617. [in Ukrainian].
  13. Shevchenko KM. Ultrastrukturni i tkaninni perebudovy miokarda peredserd shchuriv za umov vplyvu hostroi ta khronichnoi prenatalnoi hipoksii. Morfolohiia. 2015;9(3):99-110. DOI: 10.26641/1997-9665.2015.3.99-110. [in Ukrainian].
  14. Popazova O, Belenichev I, Yadlovskyi O, Oksenych V, Kamyshnyi A. Altered blood molecular markers of cardiovascular function in rats after intrauterine hypoxia and drug therapy. Curr Issues Mol Biol. 2023;45(11):8704-15. DOI: 10.3390/cimb45110547.
  15. Council of Europe. European Convention for the protection of vertebrate animals used for experimental and other scientific purposes. Strasbourg: Council of Europe; 1986. 11 p.
  16. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Off J Eur Union. 2010;L276:33-79.
  17. Kuo J. Electron microscopy: methods and protocols. Totowa, NJ: Humana Press; 2007. 608 p. DOI: 10.1007/978-1-59745-294-6.
  18. Hayat MA. Principles and techniques of electron microscopy: biological applications. 4th ed. Cambridge: Cambridge University Press; 2000. 543 p.
  19. Knoblaugh SE, Hohl TM, La Perle KMD. Pathology principles and practices for analysis of animal models. ILAR J. 2018;59(1):40-50. DOI: 10.1093/ilar/ilz001.
  20. Poslavska OV. Vyznachennia liniinykh rozmiriv ta ploshch okremykh morfolohichnykh obiektiv na mikrofotohrafiiakh za dopomohoiu prohramy ImageJ. Morfolohiia. 2016;10(3):77-81. DOI: 10.26641/1997-9665.2016.3.77-81. [in Ukrainian].
  21. Hruzieva TS, Lekhan VM, Ohniev VA, Haliienko LI, Kriachkova LV, Palamar BI. Biostatystyka. Vinnytsia: Nova Knyha; 2020. 381 s. [in Ukrainian].
  22. Romanowicz J, Guerrelli D, Dhari Z, Mulvany C, Reilly M, Swift L, et al. Chronic perinatal hypoxia delays cardiac maturation in a mouse model for cyanotic congenital heart disease. Am J Physiol Heart Circ Physiol. 2021;320(5):H1873-H1886. DOI: 10.1152/ajpheart.00870.2020.
  23. Popazova O, Belenichev I, Bukhtiyarova N, Ryzhenko V, Gorchakova N, Oksenych V, et al. Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia-Focus on the NO System. Antioxidants (Basel). 2025;14(6):743. DOI: 10.3390/antiox14060743.
  24. Sutovska H, Babarikova K, Zeman M, Molcan L. Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review. Int J Mol Sci. 2022;23(5):2885. DOI: 10.3390/ijms23052885.
  25. Hula N, Liu R, Spaans F, Pasha M, Quon A, Kirschenman R, et al. The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring. Biomedicines. 2022;10(12):3019. DOI: 10.3390/biomedicines10123019.
  26. Chatterjee P, Holody CD, Kirschenman R, Graton ME, Spaans F, Phillips TJ, et al. Sex-Specific Effects of Prenatal Hypoxia and a Placental Antioxidant Treatment on Cardiac Mitochondrial Function in the Young Adult Offspring. Int J Mol Sci. 2023;24(17):13624. DOI: 10.3390/ijms241713624.

Publication of the article:

«Bulletin of problems biology and medicine», 2025 Issue 3,178, 419-432 pages, index UDC 612.17 576.3 616-092.9 591.3.036.8

DOI:

10.29254/2077-4214-2025-3-178-419-432

Was this article helpful?

Leave a Reply

Your email address will not be published. Required fields are marked *


The reCAPTCHA verification period has expired. Please reload the page.