ABC | Volume 112, Nº1, January 2019

Original Article Jevjdovic et al Prenatal stress affects rat heart ADRB1 Arq Bras Cardiol. 2019; 112(1):67-75 1. Dong M, Zheng Q, Ford SP, Nathanielsz PW, Ren J. Maternal obesity, lipotoxicity and cardiovascular diseases in offspring. J Mol Cell Cardiol. 2013 Feb;55:111-6. 2. Roseboom TJ, van der Meulen JH, Osmond C, Barker DJ, Ravelli AC, Schroeder-Tanka JM, et al. Coronary heart disease after prenatal exposure to the Dutch famine, 1944-45. Heart. 2000;84(6):595-8. 3. Hoet JJ, Hanson MA. Intrauterine nutrition: its importance during critical periods for cardiovascular and endocrine development. J Physiol. 1999;514( Pt 3):617-27. 4. Bertram CE, Hanson MA. Prenatal programming of postnatal endocrine responses by glucocorticoids. Reproduction. 2002;124(4):459-67. 5. Igosheva N, Klimova O, Anishchenko T, Glover V. Prenatal stress alters cardiovascular responses in adult rats. J Physiol. 2004;557(Pt 1):273-85. 6. 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Analysis of beta-adrenergic receptormRNA levels inhumanventricularbiopsyspecimensbyquantitative polymerase chain reactions: progressive reduction of beta 1-adrenergic receptor mRNA in heart failure. J Am Coll Cardiol. 1996;27(1):146-54. 12. Milano CA, Allen LF, RockmanHA, Dolber PC, McMinn TR, Chien KR, et al. Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor. Science. 1994;264(5158):582-6. 13. Liggett SB, Tepe NM, Lorenz JN, Canning AM, Jantz TD, Mitarai S, et al. Early and delayed consequences of beta(2)-adrenergic receptor overexpression inmouse hearts: critical role for expression level. Circulation. 2000;101(14):1707-14. References Another protein that is involved in the sympathetic modulation of cardiac function is MAO-A. This enzyme catalyses the oxidation of monoamines during which ROS is produced and may contribute to the pathogenesis of cardiovascular diseases. 15 To the best of our knowledge this is the first study to investigate the effects of prenatal stress on cardiac MAO-A gene expression in the offspring. In the present study we did not detect significant changes in the MAO-A mRNA levels in the prenatally stressed heart of either sex. There are several limitations to this study. As mentioned above we cannot exclude the effect of limited sample size on detecting additional significant differences in region specific gene expression of myocardial beta-adrenergic receptor subpopulations. The mechanism for decreased apical myocardial ADRB1 mRNA expression in prenatally stressed female, but not male, offspring is unknown. We can only hypothesize based on available literature that sex hormones might have an effect. Thus, it would be of interest to investigate earlier developmental stages of prenatally stressed offspring. Furthermore, we did not compare cardiac expression levels of MAO-A between male and female offspring. However, based on the relative expression levels of MAO-A, we can hypothesize that our results suggest that cardiac MAO-A exhibits a sex dimorphic gene expression pattern, which is likely expressed more abundantly in the heart of male rats than in female rats. As MAO-A is a main source of hydrogen peroxide in the heart, our observation would be in agreement with the reported lower production of hydrogen peroxide in cardiac mitochondria of female, compared to male Wistar rats. 39 Conclusions In summary, our data suggest that prenatal stress may exert, already at young adult age, sex-specific changes in apical and basal cardiac adrenergic receptor subpopulations in offspring. Whether these changes correlate with diminished cardiac performance and predispose organisms to develop cardiovascular diseases during their lifetime remains to be determined in future experiments. Author contributions Conception and design of the research, statistical analysis and writing of the manuscript: Jevjdovic T; acquisition of data: Dakic T, Kopanja S; analysis and interpretation of the data: Jevjdovic T, Dakic T, Kopanja S, Lakic I, Vujovic P; o btaining financing: Djordjevic J; critical revision of the manuscript for intellectual content: Lakic I, Vujovic P, Jasnic N, Djordjevic J. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding This study was funded by The Ministry of Education, Science and Technological Development, Republic of Serbia (grant number: 173023). Study Association This article is part of the thesis of master submitted by Tanja Jevjdovic, from Faculty of Biology, University of Belgrade. Ethics approval and consent to participate This study was approved by the Ethics Committee on Animal Experiments of the FELASA), and approved by the Ethics Committee of the Faculty under the Protocol number is EK-BF-2015/25. 73