Effects of Antenatal Hypoxia on Tissue Homeostasis in the Myocardium of Albino Rats: Early and Delayed Consequences

Zubenko, S. I.; Lyu, Yan; Zhulkov, М. О.; Лебедько, О А; Сазонова, Е. Н.

doi:10.1007/s10517-014-2555-4

Cited by 6 publications

(8 citation statements)

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“…IUH induces a decrease in the DNA-synthetic activity of CMC in the developing heart. We have previously shown that albino rats exposed to IUH had a reduction in the DNA-synthetic activity of CMC at the age of 1-day old [11]. In the current study, a similar effect was shown for 7-day old animals.…”

Section: Discussionsupporting

confidence: 87%

“…Administration of NALE peptide from the 2 nd through the 6 th days of life did not normalize gravimetric indices of experimental 7-day old animals. A decrease in gravimetric indices' values under the influence of IUH is formed in the antenatal period and is detected immediately after birth in 1-day old experimental rat pups [11]. In the current study, the introduction of the peptide in the neonatal period could not lead to the rapid restoration of body mass and heart mass of experimental animals.…”

Section: Discussionmentioning

confidence: 48%

“…In 60-day old male rats subjected to IUH, we found a decrease in heart mass, a decrease in the size of the CMC nuclei, as well as a smaller total area of the nucleoli in the CMC nuclei of the left ventricle. In our previous study conducted on the same experimental model, we detected a decrease in the nucleoli number in the CMC nuclei [11]. The revealed changes may indicate the persistence of structural deficit in the myocardium of adult animals exposed to IUH, and a decrease in the functional reserves of the hearts in experimental animals [18].…”

Section: Discussionmentioning

confidence: 52%

“…In addition to impaired DNA synthesis in experimental newborn animals exposed to IUH, we detected a decline of the nucleoli number in the CMC nuclei at the ages of 1-day old [11] and 7-day old. A decrease in the nucleoli number and disruption in the structure of the CMC nucleolar complex reflects the condition of the cellular stress, and correlates with the induction of apoptosis and with increased content of p53 protein, which has both antiproliferative and proapoptotic effects on cells [15].…”

Section: Discussionmentioning

confidence: 87%

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2019

Russ Open Med J

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Objective-Our study aimed to evaluate the possibility of correcting cardiac consequences of intrauterine hypoxia (IUH) by injecting leu-enkephalin analog, lacking affinity for opiate receptors, in the early postnatal period. Material and Methods-To model IUH, we placed pregnant Wistar rats in a hypobaric chamber with an oxygen partial pressure of 52 mmHg. The procedure was repeated for 4 h daily over the 15 th-19 th days of gestation. From the 2 nd through the 6 th days of their lives, the offspring were injected intraperitoneally with non-opiate leu-enkephalin analog at a dose of 100 μg/kg (NALE: Phe-D-Ala-Gly-Phe-Leu-Arg). This analog did not have affinity for opiate receptors. The 7-and 60-day old offspring of female rats subjected to IUH were investigated. The control group included the descendants of intact animals. We investigated gravimetric indicators, DNA-synthetic activity of cardiomyocytes (CMC) by tritium-labeled thymidine autoradiography method, the size of the CMC nuclei, as well as size and amount of nucleoli in the CMC nuclei. The activity of free radical oxidation was evaluated in cardiac homogenates by chemiluminescence. Results-In 7-day old rats subjected to IUH vs. control animals, we observed decreases in body mass by 32.6%, in heart mass by 27.3%; in the proportion of 3 Н-thymidine labeled CMC nuclei by 32.7% in the left ventricle and by 30.4% in the right ventricle; in the number of nucleoli in the CMC nuclei (in the left ventricle: control-2.384±0.027, IUH-2.282±0.027*, p<0.05; in the right ventricle: control-2.409±0.038; IUH-2.240±0.012*, p<0, 05). Increase in CML indices of cardiac homogenates was revealed, indicating the activation of free radical oxidation. In 7-day old rats subjected to IUH and administration of the NALE peptide from the 2 nd through the 6 th days of their lives, the proportion of 3 H-thymidine labeled nuclei in the CMC did not differ from the control (in the left ventricle: control-12.79±0.89%, IUH + NALE-10.98±0.95%, p>0.05; in the right ventricle: control-11.61±0.78%; IUH + NALE-11.26±0.58%, p>0.05). The number of nucleoli in the CMC nuclei of the left and right ventricles in the heart of 7-day old animals in the IUH + NALE group did not differ from the control too. The CML indices of heart homogenates in the IUH + NALE group were significantly lower than those in the IUH group. In 60-day old male rats exposed to IUH, there was a decrease in heart mass by 18.5%, sizes of CMC nuclei by 7.5% and 16.1% in the left and right ventricles, respectively, and in the total nucleoli area in the CMC nuclei of the left ventricle (control-3.953±0.085; IUH-3.372±0.078*; p<0.05). In 60-day old male rats subjected to IUH and injections of the NALE peptide from the 2 nd to the 6 th days of their lives, heart mass (control-692.73±26.81 mg; IUH + NALE-631.0±29.79 mg; p>0.05) and the size of the CMC nuclei of the right ventricle (control-54.25±0.84; IUH + NALE-55.24±0.94; p>0.05) did not differ significantly from the control. The size of the nuclei, the number and size of the nucleoli ...

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 87%

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Untitled

2019

Russ Open Med J

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“…However, fetal hypoxia induced by placental embolization or placental restriction by removing maternal endometrial caruncles before conception decreased binucleation (113,596) and increased mononucleated cardiomyocytes (687) in fetal sheep. Intermittent maternal hypoxia increased the number of mononucleated cells by~150% in the left ventricle and~37% in the right ventricle of rats on postnatal day 60 (1171).…”

Section: Hypoxiamentioning

confidence: 98%

Gestational Hypoxia and Developmental Plasticity

Ducsay

Goyal

Pearce

et al. 2018

Physiological Reviews

145

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Hypoxia is one of the most common and severe challenges to the maintenance of homeostasis. Oxygen sensing is a property of all tissues, and the response to hypoxia is multidimensional involving complicated intracellular networks concerned with the transduction of hypoxia-induced responses. Of all the stresses to which the fetus and newborn infant are subjected, perhaps the most important and clinically relevant is that of hypoxia. Hypoxia during gestation impacts both the mother and fetal development through interactions with an individual's genetic traits acquired over multiple generations by natural selection and changes in gene expression patterns by altering the epigenetic code. Changes in the epigenome determine "genomic plasticity," i.e., the ability of genes to be differentially expressed according to environmental cues. The genomic plasticity defined by epigenomic mechanisms including DNA methylation, histone modifications, and noncoding RNAs during development is the mechanistic substrate for phenotypic programming that determines physiological response and risk for healthy or deleterious outcomes. This review explores the impact of gestational hypoxia on maternal health and fetal development, and epigenetic mechanisms of developmental plasticity with emphasis on the uteroplacental circulation, heart development, cerebral circulation, pulmonary development, and the hypothalamic-pituitary-adrenal axis and adipose tissue. The complex molecular and epigenetic interactions that may impact an individual's physiology and developmental programming of health and disease later in life are discussed.

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