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Background Previous studies have confirmed that nicotine exposure is an independent risk factor for miscarriage, but it is not clear whether nicotine causes unexplained recurrent spontaneous abortion (URSA) through oxidative stress. Objective To explore potential mediating effect of oxidative stress on the relationship between nicotine exposure and URSA. Methods Using a 1∶1 matched case-control study, 88 patients with URSA visiting Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University from April to October in 2018 were selected as the case group, and 88 pregnant women without adverse pregnancy outcomes and seeking induced abortion in the outpatient clinic of the same hospital were selected as the control group. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in urine were determined by enzyme-linked immunosorbent assay, and the level of urinary nicotine was determined by gas chromatography-mass spectrometry. Conditional logistic regression was used to analyze the associations of nicotine, 8-OHdG, and 8-iso-PGF2α with the risk of URSA. Multiple linear regression was used to analyze the association of nicotine with 8-OHdG and 8-iso-PGF2α. The potential mediating effect of oxidative stress on URSA after nicotine exposure was explored by dichotomous mediating model. Results The median concentrations (creatinine corrected) of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were 7.78, 4.84, and 44.10 μg·g−1, respectively, while those of the control group were 6.48, 3.34, and 29.39 μg·g−1, respectively. The concentrations of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were all higher than those of the control group (P < 0.05). The results of conditional logistic regression model showed that after adjusting selected confounding factors, compared with the Q1 groups of nicotine and 8-iso-PGF2α, the OR (95%CI) values of URSA in the Q4 groups were 4.20 (1.33-13.29) and 6.25 (1.66-23.59), respectively. Compared with the Q1 group of 8-OHdG, the OR (95%CI) values of URSA in the Q1, Q2, and Q3 groups were 5.47 (1.43-20.93), 4.24 (1.28-14.07), and 6.36 (1.82-22.28), respectively. The results of multiple linear regression showed that after adjusting confounding factors, there was a positive correlation between urinary nicotine and 8-OHdG in both the case group and the control group, and the b (95%CI) values were 0.76 (0.67-0.86) and 0.81 (0.67-0.95) respectively; there was a positive correlation between urinary nicotine and 8-iso-PGF2α in both the case group and the control group, and the b (95%CI) values were 0.65 (0.55-0.75) and 0.76 (0.64-0.87), respectively. The results of dichotomous mediating analysis showed that the mediating effect of 8-iso-PGF2α and its 95%CI on the relationship between nicotine exposure and URSA was 1.518 (0.749-2.311). Conclusion Internal nicotine exposure is a risk factor for URSA and is positively correlated with oxidative stress, and it may lead to URSA through lipid peroxidation damage.
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Background: The objective of this present study was to investigate the possible association of natural killer group (NKG) receptors gene polymorphisms and MHC class I chain-related protein A (MICA) gene polymorphism with recurrent spontaneous abortion (RSA).Methods: Three single-nucleotide polymorphism (SNPs) in NKG2D gene (rs2255336, rs2617160 and rs2617170) and one SNP in MICA gene (MICA129) rs1051792 were assessed in 100 controls and 100 patients employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis.Results: NKG2D (rs2617160) and MICA 129 (rs1051792) variants are associated with RSA risk in North Indian women.Conclusions: The NKG2D and MICA129 gene polymorphisms may influence the success of pregnancy in North Indian women population.
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Objective@#To explore the association of arsenic with unexplained recurrent spontaneous abortion (URSA).@*Methods@#A case-control study was conducted to select URSA patients who were admitted to the Beijing Maternal and Child Health Care Hospital affiliated to Capital Medical University from April to October 2018 as a case group. Women who had a normal pregnancy in the Family Planning Department of the hospital but volunteered to have an abortion were selected as a control group. The case and control group were paired in a 1: 1 ratio. The inclusion criteria of the case group were patients with newly diagnosed recurrent spontaneous abortion who had clinically confirmed more than 2 spontaneous abortions and had 20 weeks prior to pregnancy, excluding patients with recurrent spontaneous abortion caused by abnormal blood coagulation (anti-phospholipid antibody positive), abnormal physiological anatomy (B-ultrasound), abnormal immune factors (anti-nuclear antibody positive, anti-cardiolipin antibody, etc.), genetic chromosomal abnormalities (karyotype analysis) and pathogenic microbial infection. The control group was matched according to the age of the case group (±3 years old) and the gestational age (±2 weeks) to exclude adverse pregnancy outcomes such as stillbirth, congenital malformation, premature delivery and low birth weight infants. A total of 192 subjects were included. Questionnaires were used to collect information of all subjects, and 12 ml of peripheral venous blood was collected to detect blood arsenic levels. Blood arsenic levels were divided into low concentration group (<1.00 μg/L), medium concentration group (1.00-1.50 μg/L) and high concentration group (>1.50 μg/L). The multivariate conditional logistic regression was performed to analyze the relationship between blood arsenic exposure and URSA and explore the influencing factors of blood Arsenic.@*Results@#The geometric mean values of blood arsenic level in the cases group and control group were 1.68 (1.50-1.86) μg/L and 1.26 (1.17-1.37) μg/L, respectively. The blood arsenic level in the case group was significantly higher than that in the control group (P<0.05). The results of multivariate conditional logistic regression analysis showed that after adjusting for tobacco exposure during pregnancy, pre-pregnancy body mass index and the effects of residential decoration in past five years, the risk of URSA was higher in the high-concentration group compared with the low-concentration group (OR=2.56, 95%CI:1.06-6.24).@*Conclusion@#Blood arsenic may increase the risk of URSA in women of childbearing age.
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Objective · To discuss the relationship between unexplained recurrent spontaneous abortion (URSA) and T follicular helper (Tfh) cell subtypes. Methods · Twenty-eight normal early pregnancy women, who had undergone induced abortion, were taken as control, and 28 patients with URSA were enrolled in the abortion group. The mononuclear cells in peripheral blood and decidual tissues were separated in the two groups, and CXCR3+CCR6- Tfh cells, CXCR3-CCR6- Tfh cells, CXCR3-CCR6+ Tfh cells and B cells were tested by flow cytometry. Results · The decidual CXCR3-CCR6- Tfh cells significantly increased in the abortion group compared with control group (P=0.015). And there was a strong association between the decidual CXCR3-CCR6- Tfh cells and B cells in URSA patients (R2=0.779, P=0.025). Conclusion · The up-regulation of decidual CXCR3-CCR6- Tfh cells in early pregnancy women may be related with the occurrence of URSA.
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Objective To investigate the serum IL-33 level and its association with TH1,TH2,TH17 and Treg cells in patients with unexplained recurrent spontaneous abortion(URSA).Methods Forty-six URSA patients and 40 healthy controls were enrolled.The proportions of TH1,TH2,TH17 and Treg cells in peripheral blood samples were determined by flow cytometry,and serum IL-33 levels by ELISA.Results The levels of serum IL-33 in URSA patients were significantly lower than that in healthy controls.The proportions of TH2 and Treg cells in URSA patients were significantly lower than that in healthy controls (P ＜ 0.05),while the proportions of TH 1 and TH 17 cells in URSA patients were significantly higher than that in healthy controls.Serum IL-33 levels were negatively correlated with the proportions of TH 1 and TH17 cells,and positively with that of TH2 cells,while no correlation with Treg cells.Conclusion Serum IL-33 levels decrease significantly in URSA patients,and are correlated with the proportions of TH1,TH2 and TH17 cells,indicating that IL-33 may be associated with TH1,TH2 and TH17 cells in URSA patients.
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Objective · To discuss the relationship between unexplained recurrent spontaneous abortion (URSA) and T follicular helper (Tfh) cell subtypes. Methods · Twenty-eight normal early pregnancy women, who had undergone induced abortion, were taken as control, and 28 patients with URSA were enrolled in the abortion group. The mononuclear cells in peripheral blood and decidual tissues were separated in the two groups, and CXCR3+CCR6- Tfh cells, CXCR3-CCR6- Tfh cells, CXCR3-CCR6+ Tfh cells and B cells were tested by flow cytometry. Results · The decidual CXCR3-CCR6- Tfh cells significantly increased in the abortion group compared with control group (P=0.015). And there was a strong association between the decidual CXCR3-CCR6- Tfh cells and B cells in URSA patients (R2=0.779, P=0.025). Conclusion · The up-regulation of decidual CXCR3-CCR6- Tfh cells in early pregnancy women may be related with the occurrence of URSA.
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Objective: To investigate the efficacy of progesterone tablets in the patients with unexplained recurrent spontaneous abortion and the influence on cellular immunity factor.Methods: Totally 90 cases of unexplained recurrent spontaneous abortion patients were randomly divided into the observation group and the control group (45 ones in each).After pregnancy, the control group was given intramuscular injection of human chorionic gonadotropin, and the observation group started to be treated with progesterone tablets on the 35th day after menolipsis.The levels of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-17 (IL-17) and IFN-γ were determined, and the expression of T helper lymphocytes (Th17/CD4+), regulatory T lymphocytes (Treg/CD4+) and T helper lymphocytes regulatory T lymphocytes (Th17/Treg) was compared before and after the treatment.The pregnancy success rate and abortion rate were compared between the groups after the treatment, and adverse reactions were also observed.Results: After the treatment, the expression levels of IL-4 and IL-10 in the observation group were higher than those in the control group, and the expression levels of IL-17 in the observation group was lower than that in the control group, and the differences between the groups were significant (P＜0.05);after the treatment, the expression of Th17/CD4+ and Th17/Treg in the two groups decreased, and that in the observation group was lower than that in the control group;after the treatment, the expression of Treg/CD4+ in the two groups increased, and that in the observation group was higher than that in the control group, and the difference was significant (P＜0.05);after the treatment, the expression of IFN-γ in the two groups decreased, and that in the observation group was lower than that in the control group;after the treatment, the pregnancy rate in the observation group was higher than that in the control group with lower abortion rate, and the differences were statistically significant (P＜0.05).The incidence of adverse reactions in the observation group was lower than that in the control group(P＜0.05).Conclusion: Progesterone tablets in the treatment of unexplained recurrent abortion patients show significant effects, and can effectively improve the cellular immune factor in the patients, which is worth promoted application in clinics.
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Objective To discuss the correlation between MTHFR gene polymorphism and unexplained recurrent spontaneous abortion.Methods A case control study was used in this study,140 patients with unexplained recurrent spontaneous abortion(UR-SA) (abortion group)and 143 cases of normal women(control group)were recruited.Genomic DNA was obtained and extracted from the oral mucosa cells.Fluorescence quantitative PCR was used to examine the MTHFR gene polymorphisms,and Taqman-MGB technology was conducted to analysis the relationship between single nucleotide polymorphism and disease.Results There was statistically significant difference in the frequencies of C677T genotype and alleles between the two groups(P＜0.05).However,no significant difference in the frequencies of A1298C genotype and alleles between the two groups(P＞0.05).Conclusion MTHFR gene C677T polymorphism might be one of the genetic risk factors of URSA.
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Objectives To investigate the relationship of methylenetetrahydrofolate reductase (MTHFR) and methioninesynthase reductase (MTRR) with unexplained recurrent spontaneous abortion (URSA). Methods Case control study was used to select 244 patients with URSA (miscarriage group) and 116 normal women (control group) who were admitted to Tianjin Medical University General Hospital and Tianjin Women’s and Children’s Health Center from January 2013 to March 2015. The oral mucosal epithelial cells were extracted using fluorescence quantitative PCR to detect MTHFR gene C677T, A1298C and MTRR gene loci of A66G single nucleotide polymorphisms (SNP). The relationship between folate metabolism related gene polymorphisms of MTHFR and MTRR and URSA was analysed. Results The frequency of C677T genotype MTHFR was significantly higher in URSA group than that in the control group, and the frequency of CT genotype was significantly lower than that of the control group (P<0.05). There was no significant difference in the frequencies of A1298C MTRR and A66G MTHFR between the two groups. The activity of MTHFR, red cell folate and plasma folate levels were significantly lower in URSA group than those of control group. Homocysteine levels were significantly higher in URSA group than those of control group (P<0.05). There were no significant differences in serum folic acid, red cell folate, homocysteine cysteine levels between patients <35 years old and ≥ 35 years old in URSA group. Conclusion C677TMTHFR gene polymorphism is associated with unexplained recurrent spontaneous abortion.
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Objective:To investigate the role of dendritic cells(DC) in unexplained recurrent spontaneous abortion(URSA) and to study the effect and molecular mechanism of Traditional Chinese Medicine Shou Tai Decoction ( STD ) on URSA treatment by regulating the function of DC.Methods:30 cases of normal pregnancy women and 30 cases of URSA patients were taken as control group and URSA group respectively.URSA patients were treated with Shou Tai Decoction.Peripheral blood mononuclear cells were taken from both control group and URSA group before and after STD administration.The proportion of CD11c+HLA-DR+cells,CD11c+CD80+cells and CD11c+CD86+cells in peripheral blood were measured by flow cytometry.Moreover,the mRNA expression of HLA-DR,CD80,CD86 and Indoleamine2,3-dioxygenase( IDO) in venous blood were detected by RT-PCR assay.The protein expression of IDO was detected by Western blot.Furthermore, the cytokines, including IL-12p70 and IL-6, in the blood serum were measured by ELISA.Results:Compared with normal pregnancy women,the proportion of CD11c+HLA-DR+,CD11c+CD80+,CD11c+CD86+cells and the mRNA expression of HLA-DR,CD80,CD86 of URSA patients in peripheral blood were both increased significantly(P<0.05), while the mRNA and protein expression of IDO were decreased markedly(P<0.05).Additionally,the level of IL-12p70 and IL-6 in serum of URSA women were significantly increased ( P<0.01 ) .When compared with URSA patients before STD administration, the proportion of CD11c+HLA-DR+,CD11c+CD80+,CD11c+CD86+cells and the mRNA expression of HLA-DR,CD80,CD86 decreased significantly after STD administration ( P<0.05 ) , while the mRNA and protein expression of IDO increased markedly after STD administration(P<0.05).Meanwhile,compared with before STD administration,serum protein level of IL-12p70 and IL-6 of URSA patients decreased significantly after STD treatment ( P<0.01 ) .Conclusion: The changes of proportion and function of DC were involved in URSA.The regulatory effect of STD on DC proportion and function contribute to the treatment of URSA.
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Objective To discuss the correlation between the joint detection of BA,EMAb,ACA and unexplained recurrent spontaneous abortion(URSA).Methods Selected 144 URSA cases,166 SA(sporadic abortion)cases,188 normal pregnant women,and detected their BA,EMAb,ACA and statistical analysis of parallelism.Results Comparing URSA group with SA group and control group respectively,there were significant statistical difference between BA negative rate (74.31%, 25.30% and 50.53%),EMAb positive rate (35.42%,7.23% and 6.91%)and ACA positive rate (26.39%,5.42% and 5.32%)(χ2 = 19.344 ~ 74.180;P < 0.05;χ2 = 37.837 ~ 42.586,P < 0.05),(χ2 = 26.355 ~ 29.270,P < 0.05).URSA group’s BA,ACA and EMAb joint detection rate of positive (84.72%)was significantly higher than SA group and the con-trol group (χ2 =35.532~93.076,P <0.05).Conclusion There was a close relationship between the lack of BA,the genera-tion of EMAb,ACA and unexplained recurrent spontaneous abortion.Joint detection has important clinical significance in auxiliary diagnosis of unexplained recurrent spontaneous abortion and prognosis judgement.
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Objective:To investigate the role of Th1/Th2 shift in unexplained recurrent spontaneous abortion (URSA) and to study the effect and molecular mechanism of Bushen Guchong decoction on URSA treatment by regulating Th 1/Th2 paradigm.Methods:30 cases of URSA patients were given Bushen Guchong decoction administration ; meanwhile,30 cases of normal pregnancy women were taken as control group.Th1/Th2 paradigm in peripheral blood monocytes of URSA patients before and after Bushen Guchong decoction administration was detected by flow cytometry.Moreover,the mRNA expression of the specific transcription factors for Th1 and Th2 subsets -T-bet and GATA-3 were detected by RT-PCR assay.Furthermore,the relationship between the Th1/Th2 paradigm and the uterine bleeding time after Bushen Guchong decoction administration was analyzed by Pearson correlation and re -gression tests.Results: Compared with normal pregnancy women , the proportion of Th1 subset of URSA patients was increased significantly (P<0.05),while the proportion of Th2 subset was decreased markedly (P<0.05).Additionally,the ration of Th1/Th2 subsets was increased in URSA women (P<0.05).After Bushen Guchong decoction treatment ,the proportion of Th1 subsets in URSA patients and T-bet mRNA expression were up-regulated significantly ( P<0.05 ) , whereas the Th2 proportion and GATA-3 mRNA expression were down-regulated obviously (P<0.05).Moreover,the ratio of Th1/Th2 was decreased significantly (P<0.05).Correlation analysis showed that the uterine bleeding time was positively related to both the proportion of Th 1 and the ratio of Th1/Th2, while negatively related to the proportion of Th 2 subsets.Conclusion:Th1/Th2 shift was involved in URSA.Bushen Guchong decoction up-regulated the transcription level of GATA-3 and down-regulated the transcription level of T-bet.Thereby, Bushen Guchong decoction exerted the curative effect on URSA by revising Th 1/Th2 shift.
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Objective To observe the clinical curative effect of Bushen Tiaochong method on treating early unexplained recurrent spontaneous abortion (URSA). Methods 200 patients who conformed to the inclusion criteria were randomly and paralleled control study divided into two groups.The control group (routine tocolysis group,n =100 ),with 8 cases fell off. The experimental group (routine tocolysis group +traditional Chinese medicine group,n =100 ),with 10 cases fell off. Results After the treatment,the total efficiency of the control group was 70.65%,and the experimental group was 88.89%. The total efficiency of comparative difference was statistically significant (p<0.05 ). And compared the experimental group with the control group,the former group improved the level of human chorionic gonadotropin(HCG)in patients. Conclusion Bushen Tiaochong method with traditional Chinese medicine combined western medicine treatment can significantly improve the symptoms of URSA patients with threatened abortion. Compared with simple western medicine therapy,the former group has better curative effect on early unexplained recurrent spontaneous abortion.
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Objective:To investigate the possible role of NKT cells in unexplained recurrent spontaneous abortion by measuring the NKT cell numbers,maturity and cytokine secretion of the placenta of mice with unexplained recurrent spontaneous abortion.Methods:Normal pregnancy model in hybrid by feeding CBA / J and BABL/C in a cage,and the model of unexplained recurrent spontaneous abortion was established by feeding CBA / J and DBA2/J in a cage.The number of NKT and CD3~+T cells was determined by flow-cytometry;Th1/Th2-relative cytokines were assayed by ELISA and T-bet expression was determinded by fluorescence quantitative PCR.Results:There was not significant change of CD3~+ T cells when compared between normal pregnancy and unexplained recurrent spontaneous abortion group (P＞0.05).In the course of normal pregnancy,the IFN-γ secreted by placenta lymphocytes decreased gradually,accompanied by the decline of NKT cell number and the proportion of mature cells;whereas in the course of unexplained recurrent spontaneous abortion,it was on the opposite.There was significant difference of T-bet mRNA expression between the two groups.T-bet mRNA expression was related to the proportion of mature NKT cells or placenta IFN-γ secretion by lymphocytes.Conclusion:Unexplained recurrent spontaneous abortion may be related to NKT cells disorders,NKT cells are of low-mature proportion and inadequate secretion of IFN-γ during early pregnancy,whereas are shown high-mature proportion and excessive secretion of IFN-γ during latter pregnancy;the anomaly of T-bet mRNA expression may be one of the factors leading to NKT cells disorder.
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This study was undertaken to verify a specific effect of intravenous immunoglobulin treatment on the outcome of pregnancy in the patients with a history of unexplained recurrent spontaneous abortion. Five patients with a history of unexplained recurrent spontaneous abortion were treated with intravenous immunoglobulin during their following pregnancy, as soon as pregnancy was confirmed. When pregnancy was confirmed, women were started with 10 gm of immunoglobulin intravenously which was repeated every 2 weeks and four to six times. One of them experienced termination of pregnancy due to blighted ovum syndrome at 9th weeks of gestation and four patients delivered live births at term. Two of them had experienced cesarean section because of breech presentation and placenta previa respectively, rest of them delivered vaginally without problem. There were no adverse reaction in the study patients. These results imply that intravenous immunoglobulin could be effective on the patients with a history of unexplained recurrent spontaneous abortion, and could be applied to them as an alternative method of allogenic leukocyte transfusion.
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Female , Humans , Pregnancy , Abortion, Spontaneous , Breech Presentation , Cesarean Section , Immunoglobulins , Leukocyte Transfusion , Live Birth , Ovum , Placenta PreviaABSTRACT
This study was undertaken to verify a specific effect of intravenous immunoglobulin treatment on the outcome of pregnancy in the patients with a history of unexplained recurrent spontaneous abortion. Five patients with a history of unexplained recurrent spontaneous abortion were treated with intravenous immunoglobulin during their following pregnancy, as soon as pregnancy was confirmed. When pregnancy was confirmed, women were started with 10 gm of immunoglobulin intravenously which was repeated every 2 weeks and four to six times. One of them experienced termination of pregnancy due to blighted ovum syndrome at 9th weeks of gestation and four patients delivered live births at term. Two of them had experienced cesarean section because of breech presentation and placenta previa respectively, rest of them delivered vaginally without problem. There were no adverse reaction in the study patients. These results imply that intravenous immunoglobulin could be effective on the patients with a history of unexplained recurrent spontaneous abortion, and could be applied to them as an alternative method of allogenic leukocyte transfusion.