ubiquinone and Fetal-Growth-Retardation

It is well established that low birth weight and accelerated postnatal growth increase the risk of liver dysfunction in later life. However, molecular mechanisms underlying such developmental programming are not well characterized, and potential intervention strategies are poorly defined.. We tested the hypotheses that poor maternal nutrition and accelerated postnatal growth would lead to increased hepatic fibrosis (a pathological marker of liver dysfunction) and that postnatal supplementation with the antioxidant coenzyme Q10 (CoQ10) would prevent this programmed phenotype.. A rat model of maternal protein restriction was used to generate low-birth-weight offspring that underwent accelerated postnatal growth (termed "recuperated"). These were compared with control rats. Offspring were weaned onto standard feed pellets with or without dietary CoQ10 (1 mg/kg body weight per day) supplementation. At 12 mo, hepatic fibrosis, indexes of inflammation, oxidative stress, and insulin signaling were measured by histology, Western blot, ELISA, and reverse transcriptase-polymerase chain reaction.. Hepatic collagen deposition (diameter of deposit) was greater in recuperated offspring (mean ± SEM: 12 ± 2 μm) than in controls (5 ± 0.5 μm) (P < 0.001). This was associated with greater inflammation (interleukin 6: 38% ± 24% increase; P < 0.05; tumor necrosis factor α: 64% ± 24% increase; P < 0.05), lipid peroxidation (4-hydroxynonenal, measured by ELISA: 0.30 ± 0.02 compared with 0.19 ± 0.05 μg/mL per μg protein; P < 0.05), and hyperinsulinemia (P < 0.05). CoQ10 supplementation increased (P < 0.01) hepatic CoQ10 concentrations and ameliorated liver fibrosis (P < 0.001), inflammation (P < 0.001), some measures of oxidative stress (P < 0.001), and hyperinsulinemia (P < 0.01).. Suboptimal in utero nutrition combined with accelerated postnatal catch-up growth caused more hepatic fibrosis in adulthood, which was associated with higher indexes of oxidative stress and inflammation and hyperinsulinemia. CoQ10 supplementation prevented liver fibrosis accompanied by downregulation of oxidative stress, inflammation, and hyperinsulinemia.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cytokines; Diet, Protein-Restricted; Dietary Supplements; Female; Fetal Development; Fetal Growth Retardation; Hepatitis; Hyperinsulinism; Liver; Liver Cirrhosis; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Oxidative Stress; Pregnancy; Pregnancy Complications; Rats, Wistar; Specific Pathogen-Free Organisms; Ubiquinone; Weaning

Coenzyme Q10 (CoQ10 or ubiquinone) is an essential component of the mitochondrial electron transport chain and is also present in various cellular membranes and in plasma lipoproteins. Diabetes, cardiovascular, neurodegenerative, and preeclampsia diseases are all associated with an alteration of CoQ10 level or its redox status. During pregnancy, we note that the plasma content of CoQ10 is significantly higher than amniotic. In the fetal growth restriction group, amniotic total CoQ10 levels were significantly higher versus healthy, while the amniotic oxygen radical absorbing capacity level was significantly lower. A significant negative correlation was observed between amniotic total CoQ10 and birthweight. Our observation leads to the hypothesis that the amniotic midtrimester CoQ10 content may be a marker of subsequent obstetric complications.

Topics: Adult; Amniotic Fluid; Case-Control Studies; Diabetes, Gestational; Female; Fetal Growth Retardation; Fetal Membranes, Premature Rupture; Humans; Oxidative Stress; Pregnancy; Pregnancy Outcome; Reactive Oxygen Species; Risk Factors; Ubiquinone

Coenzyme Q10 (ubidecarenone) is a torpeniod molecule mainly located in bacterial and mitochondrial membranes. It is a part of a specific enzyme system and acts primarily on the transport of electrons in the mitochondrial respiratory chain. It performs an antioxidant action. We studied both fetal and maternal coenzyme Q10 plasma levels in physiological conditions and also in the presence of some pathologies.. As regards the maternal side, we selected 483 pregnancies, performing 615 blood samples, and divided them into four groups: A: physiological pregnancies; B: spontaneous abortions; C: threatened abortions; D: threatened late abortions and threatened pre-term deliveries. We then selected 61 pregnancies which differed from the previous ones and determined Q10 levels in fetal samples obtained by cordocentesis. We divided a control group from pathological groups: intra-uterine growth retardation (IUGR); Rh-isoimmunization (with intra-uterine transfusion), non immune fetal hydrops, fetal malformations. Coenzyme Q10 levels were determined in only one laboratory by high-performance liquid chromatography (HPLC). Coenzyme Q10 concentrations were expressed as mg/ml, the data as the mean + SD. Statistical analysis was performed employing a linear regression model and the student "t"-test.. After working out a normality curve of CoQ10 levels in maternal blood, we noticed that the levels of Coenzyme Q10 were low in spontaneous abortions, in threatened late abortions and in threatened pre-term deliveries. We determined the value of 0.3 mg/ml as a cutoff to differentiate the fetal from the adult values. Moreover, CoQ10 values turned out to be increased only in fetuses affected by non-immune fetal hydrops.. Accordingly, we can say that maternal CoQ10 plasma levels can be considered as a marker of pathological uterine contractile activity. There is a substantial increase in CoQ10 fetal plasma levels in fetuses affected by hypoxic hypoxia and also in those affected by non-immune fetal hydrops.

Topics: Abortion, Spontaneous; Abortion, Threatened; Adult; Antioxidants; Coenzymes; Diagnosis, Differential; Female; Fetal Blood; Fetal Diseases; Fetal Growth Retardation; Humans; Linear Models; Obstetric Labor, Premature; Pregnancy; Ubiquinone