Influence of sex and degree of prematurity on the heart structure in the late postnatal period of ontogenesis

Abstract

BACKGROUND: People born prematurely have an increased risk of early heart disease. However, to date, based on the results of clinical studies, drawing a clear conclusion about the influence of sex and degree of prematurity on the structure of the heart of people born prematurely is impossible. Experimental studies aimed at identifying the structural features of the myocardium of preterm animals depending on the sex and degree of prematurity are relevant.

AIM: To present the morphological characteristics of the left ventricle of preterm rats on days 42–180 of the postnatal period of ontogenesis, taking into account sex and degree of prematurity.

MATERIALS AND METHODS: The study was conducted on full-term, 12- and 24-h preterm male and female Wistar rats. Each group included 24 animals, including 12 males and 12 females. To obtain premature rat offspring, preterm birth was induced by antiprogestin mifepristone (10 mg/kg) injection. Histological and immunohistochemical studies of the left ventricle of premature male and female rats were performed on days 42, 56, and 180 of the postnatal period of ontogenesis. The following parameters were determined in the left ventricular wall: wall thickness, diameter and relative volume of the cardiomyocytes, and number of caspase 3-positive cardiomyocytes in 1 mm2 of the myocardium.

RESULTS: The left ventricular wall of preterm and full-term animals on days 42–180 of the postnatal period of ontogenesis has a fundamentally similar structure. However, preterm birth, regardless of sex, leads to a decrease in the relative volume of left ventricular cardiomyocytes. On day 56 of the postnatal period of ontogenesis, the number of caspase 3-positive cardiomyocytes increased only in male rats with a greater degree of prematurity.

CONCLUSION: Preterm birth influenced the relative volume of the cardiomyocytes and number of caspase 3-positive cardiomyocytes of the left ventricle; however, the influence of sex and degree of prematurity on these parameters is unclear. An earlier increase in the number of caspase 3-positive cardiomyocytes in the left ventricle of rats born 24 h preterm indicates the different adaptive potential of the myocardium of animals with different degrees of prematurity. The results of the study suggest a cardioprotective effect of female sex steroids in premature animals.

Keywords

preterm birth / heart / apoptosis / animal experimentation / rats

References

[1] Iskakov Ye B. Epidemiology of cardiovascular diseases. Medicina i jekologija. 2017;(2):19–28. EDN: DBRBMR

[2] Искаков Е. Б. Эпидемиология сердечно-сосудистых заболеваний // Медицина и экология. 2017. № 2. С. 19–28. EDN: DBRBMR

[3] Crump C, Groves A, Sundquist J, Sundquist K. Association of preterm birth with long-term risk of heart failure into adulthood. JAMA Pediatr. 2021;175(7):689–697. doi: 10.1001/jamapediatrics.2021.0131

[4] Crump C., Groves A., Sundquist J., Sundquist K. Association of preterm birth with long-term risk of heart failure into adulthood // JAMA Pediatr. 2021. Vol. 175, N 7. Р. 689–697. doi: 10.1001/jamapediatrics.2021.0131

[5] Crump C, Howell EA, Stroustrup A, et al. Association of preterm birth with risk of ischemic heart disease in adulthood. JAMA Pediatr. 2019;173(8):736–743. doi: 10.1001/jamapediatrics.2019.1327

[6] Crump C., Howell E. A., Stroustrup A., et al. Association of preterm birth with risk of ischemic heart disease in adulthood // JAMA Pediatr. 2019. Vol. 173, N 8. P. 736–743. doi: 10.1001/jamapediatrics.2019.1327

[7] Lewandowski AJ, Raman B, Bertagnolli M, et al. Association of preterm birth with myocardial fibrosis and diastolic dysfunction in young adulthood. J Am Coll Cardiol. 2021;78(7):683–692. doi: 10.1016/j.jacc.2021.05.053

[8] Lewandowski A.J., Raman B., Bertagnolli M., et al. Association of preterm birth with myocardial fibrosis and diastolic dysfunction in young adulthood // J Am Coll Cardiol. 2021. Vol. 78, N 7. Р. 683–692. doi: 10.1016/j.jacc.2021.05.053

[9] Lewandowski AJ, Lamata P, Francis JM, et al. Breast milk consumption in preterm neonates and cardiac shape in adulthood. Pediatrics. 2016;138(1): e20160050. doi: 10.1542/peds.2016-0050

[10] Lewandowski A.J., Lamata P., Francis J. M., et al. Breast milk consumption in preterm neonates and cardiac shape in adulthood // Pediatrics. 2016. Vol. 138, N 1. P. e20160050. doi: 10.1542/peds.2016-0050

[11] Dudley DJ, Branch DW, Edwin SS, Mitchell MD. Induction of preterm birth in mice by RU486. Biol Reprod. 1996;55(5):992–995. doi: 10.1095/biolreprod55.5.992

[12] Dudley D.J., Branch D. W., Edwin S. S., Mitchell M. D. Induction of preterm birth in mice by RU486 // Biol Reprod. 1996. Vol. 55, N 5. Р. 992–995. doi: 10.1095/biolreprod55.5.992

[13] Lewandowski AJ, Augustine D, Lamata P, et al. Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function. Circulation. 2013;127(2):197–206. doi: 10.1161/CIRCULATIONAHA.112.126920

[14] Lewandowski A.J., Augustine D., Lamata P., et al. Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function // Circulation. 2013. Vol. 127, N 2. Р. 197–206. doi: 10.1161/CIRCULATIONAHA.112.126920

[15] Bertagnolli M, Dios A, Béland-Bonenfant S, et al. Activation of the cardiac renin-angiotensin system in high oxygen-exposed newborn rats: angiotensin receptor blockade prevents the developmental programming of cardiac dysfunction. Hypertension. 2016;67(4):774–782. doi: 10.1161/HYPERTENSIONAHA.115.06745

[16] Bertagnolli M., Dios A., Béland-Bonenfant S., et al. Activation of the cardiac renin-angiotensin system in high oxygen-exposed newborn rats: angiotensin receptor blockade prevents the developmental programming of cardiac dysfunction // Hypertension. 2016. Vol. 67, N 4. Р. 774–782. doi: 10.1161/HYPERTENSIONAHA.115.06745

[17] Schimmel K, Ichimura K, Reddy S, et al. Cardiac fibrosis in the pressure overloaded left and right ventricle as a therapeutic target. Front Cardiovasc Med. 2022;9:886553. doi: 10.3389/fcvm.2022.886553

[18] Schimmel K., Ichimura K., Reddy S., et al. Cardiac fibrosis in the pressure overloaded left and right ventricle as a therapeutic target // Front Cardiovasc Med. 2022. Vol. 9. P. 886553. doi: 10.3389/fcvm.2022.886553

[19] Wencker D, Chandra M, Nguyen K, et al. A mechanistic role for cardiac myocyte apoptosis in heart failure. J Clin Invest. 2003;111(10):1497–1504. doi: 10.1172/JCI17664

[20] Wencker D., Chandra M., Nguyen K., et al. А mechanistic role for cardiac myocyte apoptosis in heart failure // J Clin Invest. 2003. Vol. 111, N 10. Р. 1497–1504. doi: 10.1172/JCI17664

[21] Ivanova VV, Zhigalina AS, Serebryakova ON, et al. Characteristics of myocardial blood vessels in preterm rats in the late postnatal ontogenesis. Byulleten’ eksperimental’noj biologii i mediciny. 2022;174(9):387–391. EDN: KAFIAC doi: 10.47056/0365-9615-2022-174-9-387-391

[22] Иванова В.В., Жигалина А. С., Серебрякова О. Н., и др. Характеристика кровеносных сосудов миокарда преждевременно рождённых крыс в отдалённом постнатальном периоде онтогенеза // Бюллетень экспериментальной биологии и медицины. 2022. Т. 174, № 9. С. 387–391. EDN: KAFIAC doi: 10.47056/0365-9615-2022-174-9-387-391

Funding

Российский научный фондRussian Science Foundation(24-25-00015)

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