Influence Of Prenatal Hypoxia Research Articles

Effect of Prenatal Hypoxia on the Liver of Rats

The state of the liver of one-month-old, three-month-old and six-month-old rats exposed to hypoxia during the embryonic period of intrauterine development was studied. It has been shown that prenatal hypoxia has a significant damaging effect on the liver, and the negative aspects of this factor can be traced in the later stages of ontogenesis. Histological study showed that in the liver of one-month-old experimental rats, hepatocyte hypertrophy, an increase in the size of their nuclei, and an increase in the number of binuclear hepatocytes were observed. In a comparative analysis of the data in the control and experimental groups of rats at the age of three months, no significant morphometric changes were observed. However, histological examination of the liver of three-month-old rats revealed small foci of extramedullary hematopoiesis in the parenchyma. Hemodynamic disturbances in the vessels of the liver were also determined. No significant changes in morphometric parameters were observed in the liver of the control and experimental groups of 6-month-old rats. However, melanomacrophage centers were found in the liver parenchyma, which indicates the presence of an inflammatory process. Despite the completion of the recovery processes in 6-month-old rats, the observed inflammatory processes and hemodynamic disturbances showed that prenatal hypoxia causes liver pathologies at later stages of ontogenesis. So, we can conclude that, under the influence of prenatal hypoxia, there are significant changes in the liver parenchyma, which affects the subsequent state of the body.

Prenatal hypoxia attenuated contraction of offspring coronary artery associated with decreased PKCβ Ser660 phosphorylation and intracellular calcium

AimsPrenatal hypoxia (PH) could affect peripheral vascular tone of the offspring, thus increasing the risk of cardiovascular diseases in adult. However, it's still unknown whether functions of coronary arteries (COA) in adult offspring would be influenced by PH. The present study aimed at effects of PH on vascular tone of COA and its related mechanisms. MethodsCoronary arteries of adult offspring exposed to hypoxic or normoxic circumstances during gestational day 5 to 21 were collected. Wire myograph system, whole-cell patch clamp technique, IonOptix MyoCam system, PCR, and western blot were used to detect vascular function of adult offspring COA. Key findingsPH significantly attenuated serotonin- and phorbol 12, 13-dibutyrate (PDBu)-induced constriction. Iberiotoxin potentiated PDBu-induced constriction and the effect was augmented by PH, however, no significant differences were found in whole-cell BKCa channel currents and its protein expression. Nifedipine inhibited PDBu-mediated constriction and the inhibitory effect was reduced in PH group, and whole-cell calcium channel current was decreased in offspring COA. Besides, PH reduced the capability of calcium release from the endoplasmic reticulum in COA. The phosphorylated PKCβ protein expression at Ser660 site, not Thr641 site, was significantly decreased in PH offspring. Chronic hypoxia during pregnancy attenuated PDBu-mediated constriction in offspring COA, presumably through decreased phosphorylated PKCβ at serine660 sites and decreased intracellular calcium-related weaker PKC activation. SignificanceThe findings provided new information on the influence of prenatal hypoxia on COA, and suggested potential use of PKCβ-serine660 for early prevention of coronary heart diseases in developmental origins.

Influence of Prenatal Hypoxia on the Content of Neuron Specific Enolase in the Structures of the Brain and Blood Serum of Rats in Early Ontogeny

Abstract—We studied the dynamics of changes in the content of neuron specific enolase (NSE, EC 4.2.1.11) in the hippocampus, cortex, cerebellum and blood serum of rats at 5th, 10th, and 30th days of postnatal development. It was shown that during the first month of life the content of NSE increases several-fold in all the structures studied, both after hypoxia and in the animals not exposed to hypoxia. It was established that prenatal hypoxia on the 14th day of embryonic development leads to significant changes in the NSE content in all the brain structures studied. In the blood serum, the content of this enzyme is higher in comparison with the control group on the 5th, 10th, and 30th postnatal days in experimental animals. Thus, the lack of oxygen affects the content of this enzyme in both the brain structures and in blood serum of rats, which makes it possible to judge the survival of neurons under conditions of prenatal hypoxia, and also suggests that this index may be used as a marker of fetal CNS disturbance after hypoxia during prenatal development.

On the influence of prenatal hypoxia on formation of the orexinergic system and sleep–wake cycle in early ontogenesis of rats

The role of orexin in the organization of the sleep–wake cycle (SWC) is well known. The aim of this study was to examine the timing of the orexinergic system formation in rat postnatal ontogenesis and to assess the role of orexin A in the SWC organization under normal conditions and after prenatal hypoxia undergone on days 14 and 19 of embryogenesis. The SWC was investigated in 30-day-old rats with electrodes implanted into the somatosensory and occipital cortex. Immunoreactivity within the orexigenic structures of the lateral hypothalamus was analyzed. It was shown that in control 14-day-old animals the orexinergic structures were in their formative stage, whereas in 30-day-old rats they were already as formed as in adults. In 14-day-old rats, prenatal hypoxia evoked retarded formation of the orexinergic system. In 30-day-old animals, hypoxia undergone in the prenatal period increased the activity of the orexinergic system, which was higher in animals exposed to hypoxia on day 19 than on day 14 of gestation. In 30-day-old rats, these changes were reflected in the SWC formation in the form of shorter slow-wave sleep, more fitful sleep and increased number of transitions from slow- to fast-wave sleep. The results obtained are discussed in the light of the adaptive-compensatory role of the orexigenic system in postnatal ontogenesis after prenatal damage to the central nervous system.

Chronic hypoxia in pregnancy affected vascular tone of renal interlobar arteries in the offspring.

Hypoxia during pregnancy could affect development of fetuses as well as cardiovascular systems in the offspring. This study was the first to demonstrate the influence and related mechanisms of prenatal hypoxia (PH) on renal interlobar arteries (RIA) in the 5-month-old male rat offspring. Following chronic hypoxia during pregnancy, phenylephrine induced significantly higher pressor responses and greater vasoconstrictions in the offspring. Nitric oxide mediated vessel relaxation was altered in the RIA. Phenylephrine-stimulated free intracellular calcium was significantly higher in the RIA of the PH group. The activity and expression of L-type calcium channel (Cav1.2), not T-type calcium channel (Cav3.2), was up-regulated. The whole-cell currents of calcium channels and the currents of Cav1.2 were increased compared with the control. In addition, the whole-cell K+ currents were decreased in the offspring exposed to prenatal hypoxia. Activity of large-conductance Ca2+-activated K+ channels and the expression of MaxiKα was decreased in the PH group. The results provide new information regarding the influence of prenatal hypoxia on the development of the renal vascular system, and possible underlying cellular and ion channel mechanisms involved.

The peculiarities of intermitochondrial contacts during ontogenetic formation of mitochondria network in normal and under hypoxic damage of cardiogenesis

The aim of this work was to determine the formation of intermitochondrial contacts during ontogenesis of mitochondrial reticulum and to evaluate the degree of mitochondria associations under the influence of prenatal hypoxia. In the present study, we analyzed that in normal conditions the number of intermitochondrial contacts was different in areas of the cell and changed to the stages of ontogeny. Influence of intrauterine hypoxia and oxidative stress leads to mitochondrial reactions that affects to the formation between organelles intermitochondrial contacts in the sub-sarcolemmal, intermyoflbrillar and paranuclear regions of ventricle cardiomyocytes.

Maternal Hypoxia Increases the Susceptibility of Adult Rat Male Offspring to High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease

Exposure to an adverse intrauterine environment increases the risk for adult metabolic syndrome. However, the influence of prenatal hypoxia on the risk of fatty liver disease in offspring is unclear. The purpose of the present study was to evaluate the role of reduced fetal oxygen on the development and severity of high-fat (HF) diet-induced nonalcoholic fatty liver disease (NAFLD). Based on design implicating 2 factors, ie, maternal hypoxia (MH) and postnatal HF diet, blood lipid and insulin levels, hepatic histology, and potential molecular targets were evaluated in male Sprague Dawley rat offspring. MH associated with postnatal HF diet caused a significant increase in plasma concentration of triglycerides, free fatty acids, low-density lipoprotein cholesterol, and insulin. Histologically, a more severe form of NAFLD with hepatic inflammation, hepatic resident macrophage infiltration, and progression toward nonalcoholic steatohepatitis was observed. The lipid homeostasis changes and insulin resistance caused by MH plus HF were accompanied by a significant down-regulation of insulin receptor substrate 2 (IRS-2), phosphoinositide-3 kinase p110 catalytic subunit, and protein kinase B. In MH rats, insulin-stimulated IRS-2 and protein kinase B (AKT) phosphorylation were significantly blunted as well as insulin suppression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, a significant up-regulation of lipogenic pathways was noticed, including sterol-regulatory element-binding protein-1 and fatty acid synthase in liver. Our results indicate that maternal hypoxia enhances dysmetabolic liver injury in response to an HF diet. Therefore, the offspring born in the context of maternal hypoxia may require special attention and follow-up to prevent the early development of NAFLD.

Influence of prenatal hypoxia on brain development: effects on body weight, brain weight, DNA, protein, acetylcholinesterase, 3-quinuclidinyl benzilate binding, and in vivo incorporation of [14C]lysine into subcellular fractions.

The influence of prenatal hypoxia on subsequent brain development in the young rat was investigated by examining body and brain weight, cerebral cortex wet weight, protein and DNA concentrations, acetylcholinesterase (AChE) activity, 3-quinuclidinyl benzilate (QNB)-binding levels, the relative amounts of protein in various subcellular fractions, and the in vivo incorporation of [14C]lysine into the protein of homogenate and subcellular fractions. Exposure of pregnant females to a mild hypoxia (9.1% O2, 10 h per day for the 9--11 days preceding birth) resulted in a reduced body weight in the pups and days 1 and 5 after birth; total cortical DNA was reduced but brain weight and protein content were unaffected, leading to a higher protein/DNA ratio in prenatally hypoxic pups. By 10 days of age these differences between prenatally hypoxic and control animals were no longer apparent. There were no differences between prenatally hypoxic and control animals in AChE and QNB binding per milligram cortex protein. The relative amount of synaptic membrane protein from the cerebral cortex was reduced at day 1 in prenatally hypoxic animals and the synaptic membrane fraction showed a higher level of incorporation of [14C]lysine on days 1, 5, and 10. The developmental profile of [14C]lysine incorporation showed a peak on day 10 which was higher in prenatally hypoxic rats. By 46 days after birth little difference could be found between prenatally hypoxic and control animals.