Abstract
The development of neonatology makes it possible to overcome increasingly severe degrees of prematurity. It has been established that the preterm birth in human beings is associated with a predisposition to the development of pathologies of the cardiovascular system in adulthood, but the pathogenetic mechanisms of this relationship have not been studied. In this work, we studied the effect of preterm birth on the development of the left ventricular myocardium in rats during 14 days of the postnatal period of ontogenesis. The myocardium of the left ventricle of male Wistar rats born after 21 and 21.5 days of gestation was analyzed by histology, immunohistochemistry, and morphometry (the full gestational age is 22 days). The relative heart mass of prematurely born rats exceeds that of control animals on the 14th day of the postnatal period. The diameter of the contractile cardiomyocytes of rats born on the 21st day of gestation exceeds that of full-term animals on the first day of the postnatal period of ontogenesis. Preterm birth in rats causes an increase in the number of Ki67-positive cardiomyocytes (a marker of proliferation) of the left ventricle in the early postnatal period of ontogenesis compared to full-term animals. The morphofunctional changes in the rat myocardium are more pronounced with a shorter gestational age. Preterm birth in rats is the reason for the intensification of myocardial growth in the early postnatal period of ontogenesis.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1134%2FS1990519X22010059/MediaObjects/11821_2022_7211_Fig1_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1134%2FS1990519X22010059/MediaObjects/11821_2022_7211_Fig2_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1134%2FS1990519X22010059/MediaObjects/11821_2022_7211_Fig3_HTML.gif)
Similar content being viewed by others
REFERENCES
Aye, C., Lewandowski, A.J., Lamata, P., Upton, R., Davis, E., Ohuma, E.O., Kenworthy, Y., Boardman, H., Wopperer, S., Packham, A., Adwani, S., McCormick, K., Papageorghiou, A.T., and Leeson, P., Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm, Pediatr. Res., 2017, vol. 82, p. 36.
Bensley, J.G., Stacy, V.K., De, Matteo, R., Harding, R., and Black, M.J., Cardiac remodelling as a result of pre-term birth: implications for future cardiovascular disease, Eur. Heart J., 2010, vol. 31, p. 2058.
Buhrdel, P., Willgerodt, H., Keller, E., and Theile, H., Postnatal development of rats born preterm and postterm, I. Body weight, Biol. Neonate., 1978a, vol. 33, p. 184.
Buhrdel, P., Keller, E., Willgerodt, H., and Theile, H., The postnatal development of rats born preterm and postterm, II. Liver, brain, heart and kidneys, Biol. Neonate., 1978b, vol. 33, p. 240.
Carr, H., Cnattingius, S., Granath, F., Ludvigsson, J.F., and Edstedt, Bonamy, A.K., Preterm birth and risk of heart failure up to early adulthood, J. Am. Coll. Cardiol., 2017, vol. 69, p. 2634.
Dudley, D.J., Branch, D.W., Edwin, S.S., and Mitchell, M.D., Induction of preterm birth in mice by RU486, Biol. Reprod., 1996, vol. 55, p. 992.
Goss, K.N., Haraldsdottir, K., Beshish, A.G., Barton, G.P., Watson, A.M., Palta, M., Chesler, N.C., Francois, C.J., Wieben, O., and Eldridge, M.W., Association between preterm birth and arrested cardiac growth in adolescents and young adults, JAMA Cardiol., 2020, vol. 5, p. 910.
Huckstep, O.J., Williamson, W., Telles, F., Burchert, H., Bertagnolli, M., Herdman, C., Arnold, L., Smillie, R., Mohamed, A., Boardman, H., McCormick, K., Neubauer, S., Leeson, P., and Lewandowski, A.J., Physiological stress elicits impaired left ventricular function in preterm-born adults, J. Am. Coll. Cardiol., 2018, vol. 71, p. 1347.
Ito, T., Orino, T., Harada, K., and Takada, G., Morphological maturation of left ventricle in fetal rats: changes in left ventricular volume, mass, wall thickness, and mitral valvular size, Early Hum. Dev., 1998, vol. 53, p. 1.
Ito, T., Harada, K., and Takada, G., In situ morphometric analysis of left and right ventricles in fetal rats: changes in ventricular volume, mass, wall thickness, and valvular size, Tohoku J. Exp. Med., 2001, vol. 193, p. 37.
Landim-Vieira, M., Schipper, J.M., Pinto, J.R., and Chase, P.B., Cardiomyocyte nuclearity and ploidy: when is double trouble?, J. Muscle Res. Cell Motil., 2020, vol. 41, p. 329.
Le, B., Sutherland, M.R., and Black, M.J., Maladaptive structural remodelling of the heart following preterm birth, Curr. Opin. Physiol., 2018, vol. 1, p. 89.
Lewandowski, A.J., Augustine, D., Lamata, P., Davis, E.F., Lazdam, M., Francis, J., McCormick, K., Wilkinson, A.R., Singhal, A., Lucas, A., Smith, N.P., Neubauer, S., and Leeson, P., Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function, Circulation, 2013, vol. 127, p. 197.
Lewandowski, A.J., Levy, P.T., Bates, M.L., McNamara, P.J, Nuyt, A.M., and Goss, K.N., Impact of the vulnerable preterm heart and circulation on adult cardiovascular disease risk, Hypertension, 2020, vol. 76, p. 1028.
Li, F., Wang, X., Capasso, J.M., and Gerdes, A.M., Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development, J. Mol. Cell. Cardiol., 1996, vol. 28, p. 1737.
Mohlkert, L.A., Hallberg, J., Broberg, O., Rydberg, A., Halvorsen, C.P., Liuba, P., Fellman, V., Domellöf, M., Sjöberg, G., and Norman, M., The preterm heart in childhood: left ventricular structure, geometry, and function assessed by echocardiography in 6-year-old survivors of periviable births, J. Am. Heart Assoc., 2018, vol. 7, art. e007742. https://doi.org/10.1161/JAHA.117.007742
Sullivan, M.C., Winchester, S.B., and Msall, M.E., Prematurity and cardiovascular risk at early adulthood, Child: Care, Health Dev., 2019, vol. 45, p. 71.
Toyono, M., Ito, T., Harada, K., Tamura, M., and Takada, G., Morphological adaptation of the cardiovascular system in fetal rats during late gestation, Tohoku J. Exper. Med., 1999, vol. 188, p. 299.
Vranas, S., Heinemann, G.K., Liu, H., De, Blasio, M.J., Owens, J.A., Gatford, K.L., and Black, M.J., Small size at birth predicts decreased cardiomyocyte number in the adult ovine heart, J. Dev. Origins Health Dis., 2017, vol. 8, p. 618.
Xavier-Vidal, R., Cunha, R.C., and Madi, K., Quantitative study using semithin section of the rat fetal myocardium, Revista Chilena de Anatomía, 1997, vol. 15, p. 209.
Zebrowski, D.C., Jensen, C.H., Becker, R., Ferrazzi, F., Baun, C., Hvidsten, S., Sheikh, S.P., Polizzotti, B.D., Andersen, D.C., and Engel, F.B., Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation, Sci. Rep., 2017, vol. 7, p. 8362. https://doi.org/10.1038/s41598-017-08947-2
ACKNOWLEDGMENTS
The authors express their sincere gratitude to V.Yu. Usov, the head of the department of X-ray and tomographic diagnostic methods of the Research Institute of Cardiology of Tomsk National Research Medical Center of the Russian Academy of Sciences.
Funding
This work was supported by a grant from the President of the Russian Federation for state support of young Russian scientists, decision of the Competition Commission of the Ministry of Education and Science of Russia, protocol no. 4 of December 27, 2019.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest. The authors declare that they have no conflict of interest.
Statement on the welfare of animals. Maintenance and manipulation of animals were carried out in accordance with the “Rules for Work with the Use of Experimental Animals” and in compliance with the requirements of the Council of the European Community (86/609/EEC) on the use of laboratory animals. The study protocol was approved by the decision of the local ethics committee of the Federal State Budgetary Educational Institution of Higher Education of Siberian State Medical University of the Ministry of Health of Russia no. 8475/1 dated November 30, 2020.
Rights and permissions
About this article
Cite this article
Ivanova, V.V., Milto, I.V., Serebryakova, O.N. et al. The Influence of Preterm Birth on the Development of Rat Myocardium in the Early Postnatal Period of Ontogenesis. Cell Tiss. Biol. 16, 45–51 (2022). https://doi.org/10.1134/S1990519X22010059
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1990519X22010059