scholarly journals RNA Demethylase FTO Mediated RNA m6A Modification Is Involved in Maintaining Maternal-Fetal Interface in Spontaneous Abortion

Author(s):  
Weiyu Qiu ◽  
Yuexi Zhou ◽  
Haiwang Wu ◽  
Xiaoli Lv ◽  
Lilin Yang ◽  
...  

The N6-methyladenosine (m6A) RNA modification regulates the expression of genes associated with various biological and pathological processes, including spontaneous abortion (SA). The aim of this study was to determine the role of the m6A demethylase fat mass and obesity (FTO)- associated protein in SA. The FTO,IGF2BP1 and IGF2BP2 mRNA levels were significantly lower in the chorionic villi obtained from spontaneously aborted pregnancies compared to that of normal pregnancies, while the expression levels of METTL3 and WTAP were significantly elevated. However, ALKBH5, YTHDF2, and IGF2BP3 were elevated with no statistical significance between groups. In addition, MDA was elevated and SOD levels were decreased in the villi tissues of the SA group compared to the normal group, which was indicative of placental oxidative stress in the former. Furthermore, the expression of FTO and HLA-G were significantly decreased in the trophoblasts of the SA patients compared to that of normal pregnant women, while that of m6A was markedly higher in the former. In addition, the HLA-G and VEGFR mRNA levels were downregulated in the SA versus the control group, and that of MMP2, MMP7, MMP9 and VEGFA were upregulated. Finally, The RIP assay showed significantly decreased levels of FTO-bound HLA-G, VEGFR and MMP9 RNA in SA patients (P < 0.05), which corresponded to an increase in transcripts enriched with the m6A antibody (P < 0.05). However, compared with normal pregnant women, the levels of HLA-G, VEGFA, VEGFR, and MMP2 mRNA bound by YTHDF2 were significantly decreased in SA patients. Compared to the normal pregnant women, both FTO- and m6A-bound MMP7 were significantly increased in SA patients (P < 0.05), but YTHDF2 almost unbound to MMP7 mRNA. In summary, the downregulation of FTO in the chorionic villi disrupts immune tolerance and angiogenesis at the maternal-fetal interface, resulting in aberrant methylation and oxidative stress that eventually leads to SA.

Author(s):  
Yang Yang ◽  
Jiashu Li ◽  
Yingying Zhou ◽  
Wen Dai ◽  
Weiping Teng ◽  
...  

Elevated thyroid stimulating hormone (TSH) is associated with an increased risk of spontaneous abortion (SA); however, the associated mechanism remains unclear. This study aimed to investigate the expression of microRNAs (miRNAs) and pathogenesis in the chorionic villi of TSH > 2.5 mIU/L-related SA patients. The chorionic villi were collected from pregnant women in the first trimester with TSH > 2.5 mIU/L with or without SA, as well as TSH < 2.5 mIU/L with or without SA to determine the level of miRNA expression. Differentially expressed miRNAs were confirmed by qRT-PCR in a total of 92 subjects. Cell counting kit-8 (CCK8), wound healing, transwell assays, and Western blotting were used to measure cellular biological functions and related protein in HTR-8/SVneo cells. The potential mechanisms were determined using a Luciferase reporter assay and rescue experiment. Compared with normal pregnant women, miR-17-5p was decreased and zinc finger protein 367 (ZNF367) was upregulated in the chorionic villi of TSH > 2.5 mIU/L-related SA patients. Using HTR-8/SVneo cells, we demonstrated that elevated TSH inhibited miR-17-5p expression, as well as trophoblast migration and invasion. The overexpression of miR-17-5p targeted and inhibited ZNF367 expression promoting the biological function of trophoblasts. Further studies confirmed that ZNF367 interference partially reversed the biological function of the miR-17-5p inhibitor on HTR-8/SVneo cells. Taken together, our results showed that miR-17-5p promoted biological function of trophoblasts by suppressing ZNF367.


Author(s):  
Ümit Görkem ◽  
Özgür Kan ◽  
Mehmet Ömer Bostancı ◽  
Deniz Taşkıran ◽  
Hasan Ali İnal

Objective: Spontaneous abortion is the most common complication of early pregnancy, affecting up to 20% of recognized pregnancies. Kisspeptin is predominantly released by placental syncytiotrophoblasts, and regulates their placental invasion into the uterine matrices. We aimed to establish an association of serum kisspeptin levels with pregnancy outcomes during the early gestational stage of the first trimester. Method: In this prospective study, 90 pregnant women in their 7 to 8 6/7 gestational weeks were classified into three groups: (i) The control group, consisting of healthy pregnant women (n=30), (ii) the threatened abortion group (n=30), and (iii) the spontaneous abortion group (n=30). The maternal serum samples were analyzed for complete blood count parameters and kisspeptin levels. Results: There was no statistical difference regarding body mass index (BMI) and gestational age (p=0.370). Regarding detailed obstetric notations, including gravida, parity, abortion, and living children, socioeconomic levels, and employment rates, all study groups were comparable (p>0.05, for all). No significant association was found regarding the biochemical parameters of complete blood count, including neutrophil, lymphocyte, and platelet concentrations, as well as neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) (p>0.05, for all). The median serum kisspeptin levels of the study groups did not differ between the groups (p=0.153). Correlation analysis revealed no significant relationship between serum kisspeptin levels and other study parameters in any study groups (p>0.05, for all) Conclusions: We found no statistically significant relationship between serum kisspeptin concentrations and pregnancy outcomes in the early gestational stage of the first trimester, and serum kisspeptin concentrations did not seem to be a reliable marker to distinguish abortion status from viable pregnancy


Biomedicine ◽  
2020 ◽  
Vol 39 (2) ◽  
pp. 333-338
Author(s):  
Kalaivani Manokaran ◽  
Vasanthalaxmi Krishnananda Rao ◽  
Nilima . ◽  
Manjula Shimoga Durgoji Rao ◽  
Sucheta Prasanna Kumar

Introduction and Aim: Oxidative stress plays a very important role in endosulfan-induced toxic effects on reproductive organs. Vitamin C is a potent antioxidant which plays an important role in decreasing oxidative stress. The present study was aimed to investigate the protective role of vitamin C against endosulfan-induced testicular toxicity in Wistar rats. To investigate a protective effect of vitamin C against endosulfan induced toxicity on biochemical changes. Materials and Methods: Seventy male neonatal Wistar rats were divided into  seven groups. The group  I was taken as the control group, the endosulfan-treated were grouped into II (3 mg/kg body weight (BW) and group III (6 mg/kg BW), Group IV (9 mg/kg BW) and Group V (12 mg/kg BW). Group VI (9 mg/kg BW) and group VII (12 mg/kg BW) were pretreated with vitamin C (20 mg/kg BW) for 60 days. After  the experimental procedures, the testicular weight, lactate dehydrogenase (LDH) enzyme and testosterone in plasma, LDH, steroidogenic enzymes 3?-HSD and 17?-HSD in testis were evaluated. One-way ANOVA was used to determine the statistical significance. Results: Significant improvement in the testicular weight (P<0.05) , LDH (P<0.05) levels both in plasma and testis, increase in testosterone(P<0.001) and steroidogenic enzyme levels(P<0.001) was observed in the group pretreated with vitamin C treated group when compared to the endosulfan treated group. Conclusion: Vitamin C decreases the toxic effect of endosulfan on testis. The present action might be  due to its antioxidative properties.


2010 ◽  
Vol 104 (11) ◽  
pp. 1655-1661 ◽  
Author(s):  
Ai Guo Ma ◽  
Evert G. Schouten ◽  
Yong Ye Sun ◽  
Fang Yang ◽  
Xiu Xia Han ◽  
...  

Pregnancy is a condition exhibiting increased susceptibility to oxidative stress, and Fe plays a central role in generating harmful oxygen species. The objective of the present study is to investigate the changes in haematological status, oxidative stress and erythrocyte membrane fluidity in anaemic pregnant women after Fe supplementation with and without combined vitamins. The study was a 2 months double-blind, randomised trial. Pregnant women (n 164) were allocated to four groups: group C was the placebo control group; group I was supplemented daily with 60 mg Fe (ferrous sulphate) daily; group IF was supplemented daily with Fe plus 400 μg folic acid; group IM was supplemented daily with Fe plus 2 mg retinol and 1 mg riboflavin, respectively. After the 2-month trial, Hb significantly increased by 15·8, 17·3 and 21·8 g/l, and ferritin by 2·8, 3·6 and 11·0 μg/l, in the I, IF and IM groups compared with placebo. Polarisation (ρ) and microviscosity (η) decreased significantly in other groups compared with placebo, indicating an increase in membrane fluidity. Significant decreases of ρ and η values compared with group C were 0·033 and 0·959 for group I, 0·037 and 1·074 for group IF and 0·064 and 1·865 for group IM, respectively. In addition, significant increases of glutathione peroxidase activities and decreases of malondialdehyde were shown in all treated groups, as well as increases of plasma retinol and urine riboflavin in group IM. The findings show that supplementation with Fe and particularly in combination with vitamins could improve the haematological status as well as oxidative stress and erythrocyte membrane fluidity.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Chunchun Wang ◽  
Shuting Cao ◽  
Zhuojun Shen ◽  
Qihua Hong ◽  
Jie Feng ◽  
...  

Abstract Background The objective of this experiment was to investigate the influence of dietary tributyrin on intestinal mucosa development, oxidative stress, mitochondrial function and AMPK-mTOR signaling pathway. Methods Seventy-two pigs were divided into two treatments and received either a basal diet or the same diet supplemented with 750 mg/kg tributyrin. Each treatment has six replicates of six pigs. After 14 days, 6 pigs from each treatment were selected and the jejunal samples were collected. Results Results showed that supplemental tributyrin increased (P < 0.05) villus height and villus height: crypt depth of weaned pigs. Pigs fed tributyrin had greater (P < 0.05) RNA/DNA and protein/DNA ratios than pigs on the control group. The mRNA levels of sodium glucose transport protein-1 and glucose transporter-2 in the jejunum were upregulated (P < 0.05) in pigs fed the tributyrin diet. Dietary tributyrin supplementation lowered (P < 0.05) the malondialdehyde and hydrogen peroxide (H2O2) content in jejunum, enhanced (P < 0.05) the mitochondrial function, as demonstrated by decreased (P < 0.05) reactive oxygen species level and increased (P < 0.05) mitochondrial membrane potential. Furthermore, tributyrin increased (P < 0.05) mitochondrial DNA content and the mRNA abundance of genes related to mitochondrial functions, including peroxisomal proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor A, nuclear respiratory factor-1 in the jejunum. Supplementation with tributyrin elevated (P < 0.05) the phosphorylation level of AMPK and inhibited (P < 0.05) the phosphorylation level of mTOR in jejunum compared with the control group. Conclusions These findings suggest that dietary supplementation with tributyrin promotes intestinal mucosa growth, extenuates oxidative stress, improves mitochondrial function and modulates the AMPK-mTOR signal pathway of weaned pigs.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Beatriz Hernández-Monjaraz ◽  
Edelmiro Santiago-Osorio ◽  
Edgar Ledesma-Martínez ◽  
Itzen Aguiñiga-Sánchez ◽  
Norma Angélica Sosa-Hernández ◽  
...  

Periodontal disease (PD) is one of the main causes of tooth loss and is related to oxidative stress and chronic inflammation. Although different treatments have been proposed in the past, the vast majority do not regenerate lost tissues. In this sense, the use of dental pulp mesenchymal stem cells (DPMSCs) seems to be an alternative for the regeneration of periodontal bone tissue. A quasi-experimental study was conducted in a sample of 22 adults between 55 and 64 years of age with PD, without uncontrolled systemic chronic diseases. Two groups were formed randomly: (i) experimental group (EG) n=11, with a treatment based on DPMSCs; and a (ii) control group (CG) n=11, without a treatment of DPMSCs. Every participant underwent clinical and radiological evaluations and measurement of bone mineral density (BMD) by tomography. Saliva samples were taken as well, to determine the total concentration of antioxidants, superoxide dismutase (SOD), lipoperoxides, and interleukins (IL), before and 6 months after treatment. All subjects underwent curettage and periodontal surgery, the EG had a collagen scaffold treated with DPMSCs, while the CG only had the collagen scaffold placed. The EG with DPMSCs showed an increase in the BMD of the alveolar bone with a borderline statistical significance (baseline 638.82±181.7 vs. posttreatment 781.26±162.2 HU, p=0.09). Regarding oxidative stress and inflammation markers, salivary SOD levels were significantly higher in EG (baseline 1.49±0.96 vs. 2.14±1.12 U/L posttreatment, p<0.05) meanwhile IL1β levels had a decrease (baseline 1001.91±675.5vs. posttreatment 722.3±349.4 pg/ml, p<0.05). Our findings suggest that a DPMSCs treatment based on DPMSCs has both an effect on bone regeneration linked to an increased SOD and decreased levels of IL1β in aging subjects with PD.


2021 ◽  
Author(s):  
Chunnuan Zhang ◽  
Yuheng Wang ◽  
Hongtao Ren ◽  
Junhui Wang ◽  
Dongxue Jiang ◽  
...  

Abstract The objective of this study was to determine the effects of quercetin on oxidative stress and apoptosis induced by TPT in zebrafish. 240 fish were divided into 4 groups with three repeats. D1: fish fed with the basal diet as the control group. D2: fish fed with basal diet and exposed in 10 ng/L TPT. D3: fish fed diets containing 100 mg/Kg quercetin and exposed in 10ng/L TPT. D4: fish fed diets containing 100 mg/Kg quercetin. The results showed that quercetin could ameliorate oxidative stress, which decreased MDA, NO levels and improved antioxidant enzyme activities. The key apoptotic gene expressions, including caspase3, Bax and caspase9 mRNA expression were significantly induced by TPT exposure as compared with the control group, while notably decreased the Bcl-2 gene. However, dietary quercetin prevented a significant increase in Bax, caspase3 and caspase9 mRNA levels induced by TPT exposure, but increased Bcl-2 mRNA levels. The results of our study also demonstrated that 10 ng/L TPT significantly up-regulated TNF-α, IL-1β, IL-8, and NF-kB p65 gene expression and down-regulated IL-10 and IkB expression compared to the control group. However, TPT-induced inflammation was significantly mitigated in the quercetin treatment group. In conclusion, our findings suggested that quercetin might alleviate hepatic oxidative damage and apoptosis induced by TPT.


2012 ◽  
Vol 5 (4) ◽  
pp. 179-183 ◽  
Author(s):  
Yaareb J. Mousa ◽  
Fouad K. Mohammad

ABSTRACT Oxidative stress may cause various neuronal dysfunctions and modulate responses to many centrally acting drugs. This study examines the effects of oxidative stress produced by hydrogen peroxide (H2O2) on sedation induced by diazepam or xylazine as assessed in 7-14 day-old chicks. Day-old chicks were provided with either plane tap water (control group) or H2O2 in tap water as 0.5% v/v drinking solution for two weeks in order to produce oxidative stress. Spectrophotometric methods were used to determine glutathione and malondialdehyde concentrations in plasma and whole brain. Drug-induced sedation in the chicks was assessed by monitoring the occurrence of signs of sedation manifested as drooping of the head, closed eyelids, reduced motility or immotility, decreased distress calls, and recumbency. The latency to onset of sedation and its duration were also recorded. H2O2 treatment for two weeks significantly decreased glutathione and increased malondialdehyde concentrations in plasma and whole brain of the chicks on days 7, 10 and 14 as compared with respective age-matched control groups. H2O2 decreased the median effective doses of diazepam and xylazine for the induction of sedation in chicks by 46% and 63%, respectively. Injection of diazepam at 2.5, 5 and 10 mg/kg, i.m. or xylazine at 2, 4 and 8 mg/kg, i.m. induced sedation in both control and H2O2-treated chicks in a dose dependent manner, manifested by the above given signs of sedation. H2O2 significantly decreased the latency to onset of sedation in chicks treated with diazepam at 5 and 10 mg/kg, increased the duration of sedation and prolonged the total recovery time in comparison with respective non-stressed control chicks. A similar trend occurred with xylazine in the H2O2-treated chicks, though the differences from control counterparts did not attain the statistical significance, except for the recovery time of the lowest dose of the drug. The data suggest that H2O2-induced oxidative stress sensitizes the chicks to the depressant action of the sedatives diazepam and xylazine. Further studies are needed to examine the potential role of oxidative stress in modulating the actions of therapeutic agents on the brain.


2021 ◽  
Author(s):  
Xiang Yan ◽  
Meng Fu ◽  
Ye Gao ◽  
Qin Han ◽  
Shuang Li ◽  
...  

Abstract Background Delayed neuropsychologic sequelae is common in patients after carbon monoxide poisoning without effective methods worldwide. Fasudil exerts neuroprotective effect and alleviates oxidative stress in some neurodegenerative disorders. However, the mechanism between DNS and FS remains unclear. The study aims to explore the efficacy and mechanism of Fasudil in DNS mice model. Objective The delayed neuropsychologic sequelae model was induced with a hyperbaric oxygen chamber. All rats were randomly assigned to three groups (n=10): air control group (AC), CO poisoning group (CO), and CO poisoning +Fasudil group (CO+FS). Rats in the CO+FS group were given Fasudil (10 mg/kg/day, ip). The morris water maze was documented to estimate spatial learning and memory of mice. The demyelination state in brain was observed through LFB staining. The protein of MBP was examined with immunofluorescence staining. The levels of IL-6, TNF-α, TGF-β, SOD, and MDA were examined by ELISA. The mRNA levels of Rho, ROCK2, MLC1 and MYPT1 were analyzed by rt-PCR. Result The cognitive impairment in the CO+FS group were significantly reduced than those of the CO group (P<0.05). LFB staining and immunofluorescence staining of MBP results showed that FS significantly treatment attenuated demyelination (P<0.05). Compared with the CO group, the levels of TNF-α, IL-6, MDA, ROCK2, MLC1, and MYPT1 significantly decreased (P<0.05), and the levels of SOD were significantly increased in the CO+FS group (P<0.05). Conclusion In a word, Fasudil attenuated delayed neuropsychologic sequelae by inhibiting inflammation, oxidative stress and downregulating Rho/ROCK pathway in DNS mice model. We conclude that Fasudil may be a novel treatment for delayed neuropsychologic sequelae.


Author(s):  
Anna Nevolina ◽  
Natalia Safonova ◽  
Maria Proskura

Background sVEGFR1 is a hypoxia influenced growth factor, involved in the endothelial dysfunction characterizing the pregnancy disorder of preeclampsia. Objective Determine correlation between dynamic pattern of sVEGFR1 serum concentration and complications in pregnant women with antenatal fetal death history for timely diagnosis. Materials and Methods A total of 35 women in the second and third trimester of pregnancy were enrolled in the study group and 30 women – in the control group. The study group was divided into 3 subgroups: subgroup #1: pregnant women, with no placental insufficiency (n=21), subgroup #2 - pregnant women with PI (n=8), subgroup #3 - pregnant women with PI resulting in preeclampsia(n=6). The control group comprised 30 pregnant women with uncomplicated childbirth. sVEGFR1 concentration was estimated in maternal serum by means of enzyme multiplied immune assay Quantikine (R and D systems, USA and Canada). Statistical data was assessed by SPSS statistics. Package was used to perform all the statistical analysis. The conventional p≤0,05 was used to assess statistical significance. Results Average age of women in the study group was 28,4±4,7 years, in the control group – 27,7±4,7 years. A physiological sVEGFR1 serum concentration was observed in the subgroup #1. As well as that, this group demonstrated concordant to the healthy pregnant women fluctuations of sVEGRF1 serum concentration. However, sVEGRF1 level was 1,2 fold less than in the control group during 29-32, 33-36 weeks of pregnancy. It was statistically proven, that fluctuations in sVEGRF1 serum concentration in the subgroup #2 were similar to the ones in the control group. No statistically significant changes of sVEGRF1 serum concentration compared to the control group were detected in the subgroup #3 up to the 28th week of pregnancy. However, a 1,5 fold increase of sVEGFR1 concentration was observed in the subgroup #3 (p<0,005) in comparison with the control group (1586±358 pg/ml, 2347±519 pg/ml, 3695±1547 pg/ml during 29-32, 33-36, >37 weeks of pregnancy, respectively). Control group demonstrated physiological concentration of sVEGRF1 throughout the pregnancy. Conclusion Changes in sVEGFR1 serum concentration were statistically significant in the group of pregnant women with PI, resulting in preeclampsia. Moreover, they were detected 3-4 weeks prior to clinical symptoms, providing opportunity for timely diagnosis and prevention measures.


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