Angiogenesis and oxidative stress-related gene variants in recurrent pregnancy loss

2018 ◽  
Vol 30 (3) ◽  
pp. 498 ◽  
Author(s):  
Marcela Felix Fortis ◽  
Lucas Rosa Fraga ◽  
Juliano André Boquett ◽  
Thayne Woycinck Kowalski ◽  
Caroline Gross Dutra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Normal Pregnancy ◽  
Susceptibility Factors ◽  
Increased Risk ◽  
Prostaglandin Endoperoxide Synthase ◽  
Oxide Synthase ◽  
Endothelial Growth Factor

Recurrent pregnancy loss (RPL) affects ~3–5% of couples attempting to conceive and in around 50% of cases the aetiology remains unknown. Adequate vascularisation and placental circulation are indispensable for the development of a normal pregnancy. Prostaglandin-endoperoxide synthase 2 (PTGS2), vascular endothelial growth factor (VEGF) and the nitric oxide (NO) systems play important roles in reproductive physiology, participating in several steps including implantation and apoptosis of trophoblast cells. In this study we evaluated genetic polymorphisms in the inducible nitric oxide synthase (NOS2), PTGS2 and VEGFA genes as susceptibility factors for RPL. A case-control study was conducted in 149 women having two or more miscarriages and 208 controls. Allele and genotype distributions of the polymorphisms studied in the two groups were not statistically different. However, the dominant model showed that the presence of variant T (TT/GT) of rs2779249 (−1290G > T) of NOS2 was significantly associated with RPL (OR = 1.58, CI 95% = 1.03–2.44; P = 0.037). The increased risk remained significant when adjusted for number of pregnancies, alcohol consumption and ethnicity (OR = 1.92, CI95% = 1.18–3.11; P = 0.008). These results suggest that the variant genotypes of the functional polymorphism rs2779249 in the NOS2 promoter are a potential risk for RPL, possibly due to oxidative stress mechanisms.

scholarly journals Systematic review and meta-analysis of female lifestyle factors and risk of recurrent pregnancy loss

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ka Ying Bonnie Ng ◽  
George Cherian ◽  
Alexandra J. Kermack ◽  
Sarah Bailey ◽  
Nick Macklon ◽  
...  
Keyword(s):  
Systematic Review ◽  
General Population ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Meta Analysis ◽  
Lifestyle Factors ◽  
Caffeine Intake ◽  
Increased Risk ◽  
Secondary Outcomes

AbstractIt is known that lifestyle factors affect sporadic miscarriage, but the extent of this on RPL (recurrent pregnancy loss) is less well known. A systematic review and meta-analysis was performed to assess the associations between lifestyle factors and RPL. Studies that analysed RPL in the context of BMI, smoking, alcohol and caffeine intake were included. The primary and secondary outcomes were odds of having RPL in the general population and odds of further miscarriage, respectively. Underweight and women with BMI > 25 are at higher odds of RPL in the general population (OR 1.2, 95% CI 1.12–1.28 and OR 1.21, 95% CI 1.06–1.38, respectively). In women with RPL, having BMI > 30 and BMI > 25 has increased odds of further miscarriages (OR 1.77, 95% CI 1.25–2.50 and OR 1.35, 95% CI 1.07–1.72, respectively). The quality of the evidence for our findings was low or very low. Being underweight and BMI > 25 contributes significantly to increased risk of RPL (general population). BMI > 25 or BMI > 30 increases the risk of further miscarriages (RPL population). Larger studies addressing the effects of alcohol, cigarette smoking and caffeine on the risk of RPL with optimisation of BMI in this cohort of women are now needed.

Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury

2021 ◽  
pp. 096032712199944
Author(s):  
Mohamed IA Hassan ◽  
Fares EM Ali ◽  
Abdel-Gawad S Shalkami
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Liver Enzymes ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Aim: Hepatic ischemia/reperfusion (I/R) injury is a syndrome involved in allograft dysfunction. This work aimed to elucidate carvedilol (CAR) role in hepatic I/R injury. Methods: Male rats were allocated to Sham group, CAR group, I/R group and CAR plus I/R group. Rats subjected to hepatic ischemia for 30 minutes then reperfused for 60 minutes. Oxidative stress markers, inflammatory cytokines and nitric oxide synthases were measured in hepatic tissues. Results: Hepatocyte injury following I/R was confirmed by a marked increase in liver enzymes. Also, hepatic I/R increased the contents of malondialdehyde however decreased glutathione contents and activities of antioxidant enzymes. Furthermore, hepatic I/R caused elevation of toll-like receptor-4 (TLR-4) expression and inflammatory mediators levels such as tumor necrosis factor-α, interleukin-6 and cyclooxygenase-II. Hepatic I/R caused down-regulation of endothelial nitric oxide synthase and upregulation of inducible nitric oxide synthase expressions. CAR treatment before hepatic I/R resulted in the restoration of liver enzymes. Administration of CAR caused a significant correction of oxidative stress and inflammation markers as well as modulates the expression of endothelial and inducible nitric oxide synthase. Conclusions: CAR protects liver from I/R injury through reduction of the oxidative stress and inflammation, and modulates endothelial and inducible nitric oxide synthase expressions.

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes

1998 ◽  
Vol 274 (1) ◽  
pp. C245-C252 ◽  
Author(s):  
Junsuke Igarashi ◽  
Masashi Nishida ◽  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Hiroaki Kosaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiac Myocytes ◽  
Myocardial Injury ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor ◽  
Oxide Synthase ◽  
Gpx Activity

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

scholarly journals Endothelial dysfunction and body mass index: is there a role for plasma peroxynitrite?

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Theresa Chikopela ◽  
Douglas C. Heimburger ◽  
Longa Kaluba ◽  
Pharaoh Hamambulu ◽  
Newton Simfukwe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Body Mass ◽  
Vascular Function ◽  
Aortic Ring ◽  
Normal Weight ◽  
Oxide Synthase ◽  
Weight Groups

Abstract Background Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo) in underweight persons. The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight, normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15–20 h post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial-dependent and endothelial-independent vascular relaxation after pre-constriction of aortic rings with phenylephrine. Results Nitrotyrosine levels in saline-treated rats were similar among the weight groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, Rmax (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower Rmax in the underweight rats (106%) compared to the normal weight rats (112%). Overweight rats had a significant decrease in Rmax (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower Rmax accompanied an increase in peroxynitrite after acetylcholine challenge in all weight groups. Conclusions Endothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction.

scholarly journals Association of Tumor Necrosis Factor-α -308G>A, -238G>A and -376G>A polymorphisms with recurrent pregnancy loss risk in the Greek population

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sofoklis Stavros ◽  
Despoina Mavrogianni ◽  
Myrto Papamentzelopoulou ◽  
Evaggelos Basamakis ◽  
Hend Khudeir ◽  
...  
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Pcr Amplification ◽  
Greek Population ◽  
Control Group ◽  
Increased Risk ◽  
Tnf Α ◽  
Caucasian Women ◽  
Factor Α ◽  
And Control

Abstract Background Promoter region SNPs in TNF-α have been studied in association with Recurrent Pregnancy Loss (RPL) occurrence in various populations. Among them, −238G > A, −308G > A and − 376G > A have been frequently investigated for their potential role in recurrent abortions. The aim of the present study is to evaluate the correlation among TNF-α 238, TNF-α 308 and TNF-α 376 polymorphisms and recurrent pregnancy loss risk in Greek women. Methods This study included 94 Caucasian women with at least two miscarriages of unexplained aetiology, before the 20th week of gestation. The control group consisted of 89 Caucasian women of proven fertility, with no history of pregnancy loss. DNA samples were subjected to PCR amplification using specific primers. Sanger sequencing was applied to investigate the presence of TNF-α 238, TNF-α 308, TNF-α 376 polymorphisms in all samples. Results The TNF-α 238 and TNF-α 308 variants were both detected in RPL and control groups (7.45% vs 4.49 and 45.16% vs 36.73%, respectively), but with no statistically significant association (p-value 0.396 and 0.374, respectively). The TNF-α 376 variant was not detected at all in both control and RPL groups. When TNF-α 238 and TNF-α 308 genotypes were combined no association with RPL was detected (p-value = 0.694). In subgroup analysis by parity, RPL patients carrying the A allele reported less previous births. Conclusions This is the first study demonstrating TNF-α 238 and TNF-α 308 gene expression and the absence of TNF-α 376 variant in Greek women with RPL. However, no association emerged between each polymorphism studied and the occurrence of recurrent pregnancy loss. Accordingly, TNF-α -308G > A, −238G > A and -376G > A variants are not considered genetic markers for identifying women at increased risk of recurrent pregnancy loss in the Greek population.

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