Glutathione and oxidized nicotinamide adenine dinucleotide (NAD+) redox status in plasma and placental tissue of Saudi patients with intrauterine growth restriction

Abstract Background Few studies are available on the mechanism of intestinal dysfunction in newborn piglets with intrauterine growth restriction (IUGR). This work aimed to study the mechanism of jejunum dysfunction in IUGR newborn piglets through RNA-seq and improve their performance by dimethylglycine sodium salt (DMG-Na) supplementation after weaning. Methods In total, 13 normal birth weight (NBW) newborn piglets and 23 IUGR newborn piglets were obtained. Among them, 3 NBW and 3 IUGR newborn piglets were selected and stunned by electric shock after birth without suckling and collected the jejunum samples for RNA-sEq. After weaning at 21 days, they were randomly assigned to 3 groups (n = 10): NBW weaned piglets fed with common basal diets (N); IUGR weaned piglets fed with common basal diets (I); IUGR weaned piglets fed with common basal diets plus 0.1% DMG-Na (ID). All piglets are slaughtered at 49 days of age to collect serum and jejunum samples. Results The hub genes, including ATP8, C11orf86, CDKN1C, DDX58. HPX, INHBB, LECT2, ND1, NFIX, PRDM5, PSD3, SCD, and ZNF770, were found from the data analyzed by RNA-seq and WGCNA. Interestingly, we found ATP8 was the most significantly changed gene, which was crucial in maintaining mitochondrial function. After weaning, the growth performance of ID group was improved (P < 0.05) compared to that in I group. Jejunum histological morphology and its sub-organelle ultrastructure, serum immunoglobulin, jejunum sIgA level, and jejunum digestive enzyme activity were improved (P < 0.05) in ID group compared to those in I group. The redox status of serum, jejunum and its mitochondrial, as well as jejunum redox status-related and mitochondrial function-related gene expression level and protein content were improved (P < 0.05) in ID group in comparison to those in I group. Conclusion The activity of the SIRT1/PGC1α pathway was inhibited in the IUGR weaned piglets, which in turn leads to damage to their redox status and jejunum structure and function, and finally lowers their performance. The IUGR weaned piglets activate the SIRT1/PGC1α pathway by taking in the antioxidant substance like DMG-Na, thereby improving their unfavorable body state.

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The role of apoptosis in the complex pathogenesis of the most common obstetrics and gynaecology diseases

Physiology International ◽

10.1556/2060.2020.00014 ◽

2020 ◽

Vol 107 (1) ◽

pp. 106-119

Author(s):

P. Kovács ◽

József Gábor Joó ◽

V. Tamás ◽

Z. Molnár ◽

D. Burik-Hajas ◽

...

Keyword(s):

Gene Expression ◽

Intrauterine Growth Restriction ◽

Placental Tissue ◽

Growth Restriction ◽

Tissue Samples ◽

Intrauterine Growth ◽

Pcr Method ◽

Bax Gene ◽

Gene Expression Levels

AbstractPurposeWe aimed to assess the etiological role of apoptotic genes Bcl-2 and Bax in the background of major obstetric and gynaecological diseases.MethodsPlacental tissue samples were collected from 101 pregnancies with intrauterine growth restriction and 104 pregnancies with premature birth with 140 controll samples from term, eutrophic newborns. In addition, gene expression assessment of the genes Bax and Bcl-2 was performed in 101 uterine leiomyoma tissue samples at our disposal with 110 control cases. Gene expression levels were assessed by PCR method.ResultsThe expression of the Bcl-2 gene was decreased in placental samples with intrauterine growth restriction. Significant overexpression of the proapoptotic Bax gene was detected in samples from premature infants. Antiapoptotic Bcl-2 gene expression was found to be significantly increased in fibroid tissues.ConclusionApoptosis plays a crucial role in the development of the most common OB/GYN conditions. Decrease in the placental expression of the antiapoptotic gene Bcl-2 may upset the balance of programmed cell death.

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Major differences in the levels of redox status and antioxidant defence markers in the erythrocytes of pre- and full-term neonates with intrauterine growth restriction

Reproductive Toxicology ◽

10.1016/j.reprotox.2015.02.008 ◽

2015 ◽

Vol 53 ◽

pp. 10-14 ◽

Cited By ~ 9

Author(s):

Ágnes Ferencz ◽

Hajnalka Orvos ◽

Edit Hermesz

Keyword(s):

Intrauterine Growth Restriction ◽

Redox Status ◽

Full Term ◽

Growth Restriction ◽

Antioxidant Defence ◽

Term Neonates ◽

Intrauterine Growth

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Effects of Early Resveratrol Intervention on Skeletal Muscle Mitochondrial Function and Redox Status in Neonatal Piglets with or without Intrauterine Growth Retardation

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4858975 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Kang Cheng ◽

Ting Wang ◽

Simian Li ◽

Zhihua Song ◽

Hao Zhang ◽

...

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Function ◽

Growth Retardation ◽

Nicotinamide Adenine Dinucleotide ◽

Intrauterine Growth Retardation ◽

Redox Status ◽

Nicotinamide Adenine ◽

Reduced Form ◽

Mitochondrial Morphology ◽

Intrauterine Growth

Skeletal muscle mitochondrial malfunction of offspring induced by intrauterine growth retardation (IUGR) may be a contributor to growth restriction and metabolic disorder at various periods of life. This study explored the effects of IUGR and resveratrol (RSV) on mitochondrial function and redox status in the longissimus dorsi muscle (LM) of piglets during the sucking period. A total of 36 pairs of IUGR and normal birth weight male piglets were orally fed with either 80 mg RSV/kg body weight/d or 0.5% carboxymethylcellulose sodium during days 7-21 after birth. The results showed that RSV treatment improved anomalous mitochondrial morphology, increased adenosine triphosphate and glycogen contents, and enhanced nicotinamide adenine dinucleotide/reduced form of nicotinamide-adenine dinucleotide ratio in the LM of IUGR piglets. Moreover, the IUGR-induced increased malondialdehyde and protein carbonyl concentrations, abnormal mtDNA number, and suppressed genes expression of mitochondrial biogenesis such as nuclear respiratory factor 1, estrogen-related receptor alpha, and polymerase gamma in the LM were restored to some extent by RSV treatment. Additionally, RSV increased mitochondrial complex V activity in the LM of piglets. Collectively, RSV administration alleviated the LM mitochondrial dysfunction and oxidative damage of IUGR piglets.

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Placental mitochondrial content and function in intrauterine growth restriction and preeclampsia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00426.2013 ◽

2014 ◽

Vol 306 (4) ◽

pp. E404-E413 ◽

Cited By ~ 83

Author(s):

C. Mandò ◽

C. De Palma ◽

T. Stampalija ◽

G. M. Anelli ◽

M. Figus ◽

...

Keyword(s):

Oxygen Consumption ◽

Intrauterine Growth Restriction ◽

Placental Tissue ◽

Growth Restriction ◽

Elective Cesarean Section ◽

Mrna Levels ◽

Respiratory Chain Complexes ◽

Mitochondrial Content ◽

Intrauterine Growth ◽

Cytotrophoblast Cells

Intrauterine growth restriction (IUGR) and pregnancy hypertensive disorders such as preeclampsia (PE) associated with IUGR share a common placental phenotype called “placental insufficiency”, originating in early gestation when high availability of energy is required. Here, we assess mitochondrial content and the expression and activity of respiratory chain complexes (RCC) in placental cells of these pathologies. We measured mitochondrial (mt)DNA and nuclear respiratory factor 1 ( NRF1) expression in placental tissue and cytotrophoblast cells, gene and protein expressions of RCC (real-time PCR and Western blotting) and their oxygen consumption, using the innovative technique of high-resolution respirometry. We analyzed eight IUGR, six PE, and eight uncomplicated human pregnancies delivered by elective cesarean section. We found lower mRNA levels of complex II, III, and IV in IUGR cytotrophoblast cells but no differences at the protein level, suggesting a posttranscriptional compensatory regulation. mtDNA was increased in IUGR placentas. Both mtDNA and NRF1 expression were instead significantly lower in their isolated cytotrophoblast cells. Finally, cytotrophoblast RCC activity was significantly increased in placentas of IUGR fetuses. No significant differences were found in PE placentas. This study provides genuine new data into the complex physiology of placental oxygenation in IUGR fetuses. The higher mitochondrial content in IUGR placental tissue is reversed in cytotrophoblast cells, which instead present higher mitochondrial functionality. This suggests different mitochondrial content and activity depending on the placental cell lineage. Increased placental oxygen consumption might represent a limiting step in fetal growth restriction, preventing adequate oxygen delivery to the fetus.

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