Occurrence Of Recurrent Miscarriage Research Articles

INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion.

The INO80 complex, a SWI/SNF family chromatin remodeler, has regulatory effects on ESC self‐renewal, somatic cell reprogramming and blastocyst development. However, the role of INO80 in regulating trophoblast cells and recurrent miscarriage (RM) remains elusive. To investigate the in vivo effects of Ino80 in embryo development, we disrupted Ino80 in C57 mice, which resulted in embryonic lethality. Silencing of Ino80 led to decreased survival capacity, migration and invasion of trophoblasts. Furthermore, RNA high‐throughput sequencing (RNA‐seq) revealed that Ino80 silencing closely resembled the gene expression changes in RM tissues. To investigate the mechanisms for these results, RNA‐seq combined with high‐throughput sequencing (ChIP‐seq) was used in trophoblast cells, and it showed that Ino80 physically occupies promoter regions to affect the expression of invasion‐associated genes. Last, Western blotting analyses and immunofluorescence staining revealed that the content of INO80 was reduced in RM patients compared to in healthy controls. This study indicates that INO80 has a specific regulatory effect on the viability, migration and invasion of trophoblast cells. Combined with its regulation of the expression of invasion‐associated genes, it has been proposed that epigenetic regulation plays an important role in the occurrence of RM, potentially informing RM therapeutic strategies.

DNA methylation profiling in recurrent miscarriage.

Recurrent miscarriage (RM) is a complex clinical problem. However, specific diagnostic biomarkers and candidate regulatory targets have not yet been identified. To explore RM-related biological markers and processes, we performed a genome-wide DNA methylation analysis using the Illumina Infinium HumanMethylation450 array platform. Methylation variable positions and differentially methylated regions (DMRs) were selected using the Limma package in R language. Thereafter, gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on these DMRs. A total of 1,799 DMRs were filtered out between patients with RM and healthy pregnant women. The GO terms were mainly related to system development, plasma membrane part, and sequence-specific DNA binding, while the enriched pathways included cell adhesion molecules, type I diabetes mellitus, and ECM–receptor interactions. In addition, genes, including ABR, ALCAM, HLA-E, HLA-G, and ISG15, were obtained. These genes may be potential candidates for diagnostic biomarkers and possible regulatory targets in RM. We then detected the mRNA expression levels of the candidate genes. The mRNA expression levels of the candidate genes in the RM group were significantly higher than those in the control group. However, additional research is still required to confirm their potential roles in the occurrence of RM.

Genetics of recurrent pregnancy loss among Iranian population.

BackgroundRecurrent pregnancy loss (RPL) is one of the most common reproductive disorders which is defined as the occurrence of recurrent miscarriage before 24 weeks of gestation and is observed among 1%–5% of women.MethodsVarious factors are associated with RPL such as immunological disorders, maternal age, obesity, alcohol, chromosomal abnormality, endocrine disorders, and uterine abnormalities. About half of the RPL cases are related with chromosomal abnormalities. Therefore, RPL genetic tests are mainly limited to karyotyping. However, there is a significant proportion of RPL cases without any chromosomal abnormalities that can be related to the single‐gene aberrations. Therefore, it is required to prepare a diagnostic panel of genetic markers besides karyotyping.ResultsIn the present review, we have summarized all the significant reported genes until now which are associated with RPL among Iranian women. We categorized all the reported genes based on their cellular and molecular functions in order to determine the molecular bases of RPL in this population.ConclusionThis review paves the way of introducing a population‐based diagnostic panel of genetic markers for the first time among Iranian RPL cases. Moreover, this review clarifies the genetic and molecular bases of RPL in this population.

Oral sex is associated with reduced incidence of recurrent miscarriage

A possible way of immunomodulation of the maternal immune system before pregnancy would be exposure to paternal antigens via seminal fluid to oral mucosa. We hypothesized that women with recurrent miscarriage have had less oral sex compared to women with uneventful pregnancy.In a matched case control study, 97 women with at least three unexplained consecutive miscarriages prior to the 20th week of gestation with the same partner were included. Cases were younger than 36 years at time of the third miscarriage. The control group included 137 matched women with an uneventful pregnancy. The association between oral sex and recurrent miscarriage was assessed with conditional logistic regression, odds ratios (ORs) were estimated. Missing data were imputed using Imputation by Chained Equations.In the matched analysis, 41 out of 72 women with recurrent miscarriage had have oral sex, whereas 70 out of 96 matched controls answered positive to this question (56.9% vs. 72.9%, OR 0.50 95%CI 0.25−0.97, p = 0.04). After imputation of missing exposure data (51.7%), the association became weaker (OR 0.67, 95%CI 0.36–1.24, p = 0.21).In conclusion, this study suggests a possible protective role of oral sex in the occurrence of recurrent miscarriage in a proportion of the cases. Future studies in women with recurrent miscarriage explained by immune abnormalities should reveal whether oral exposure to seminal plasma indeed modifies the maternal immune system, resulting in more live births.

Can Porphyromonas gingivalis be a novel aetiology for recurrent miscarriage?

Objective To study the association between Porphyromonas gingivalis (P. gingivalis) infection and recurrent miscarriage.Methods This case control study included women with early pregnancy failure admitted for surgical evacuation of retained products of conception. Cases (group 1) included 50 women with unexplained recurrent early miscarriage whereas the control group (group 2) consisted of 50 women with no such history. The evacuated products of conception, subgingival plaques, cervicovaginal secretions and saliva of all participants were examined to detect P. gingivalis deoxyribonucleic acid (DNA) using a polymerase chain reaction.Results The prevalence of P. gingivalis DNA in the chorionic villous tissue samples of group 1 was significantly higher than in group 2 (8 [16%] vs. 1 [2%], respectively; p = 0.036, odds ratio [OR]: 9.3, 95% confidence interval [CI]: 1.1–76.9). The prevalence of P. gingivalis DNA was significantly higher in cervicovaginal secretions of group 1 than in group 2 (9 [18%] vs. 1 [2%], respectively; p = 0.02, OR: 10.8, 95% CI: 1.3–88.5). On the contrary, P. gingivalis DNA could not be detected in subgingival plaques and saliva samples of either group.Conclusion The current study found an association between P. gingivalis infection of the female genital tract and the occurrence of recurrent miscarriage.Chinese 摘要目的：研究牙龈卟啉单胞菌（P. gingivalis）感染与复发性流产的相关性。方法：这项病例对照研究纳入的研究对象为早期妊娠失败、并需手术清除妊娠残留物的患者。病例组（组1）包括50名不明原因复发性流产的患者，而对照组（组2）包括50名没有这种病史的女性。使用聚合酶链反应检测所有参与者抽吸的妊娠物、牙龈下菌斑、宫颈阴道分泌物和唾液中的牙龈卟啉单胞菌脱氧核糖核酸（DNA）。结果：组1的绒毛膜组织样本中牙龈卟啉单胞菌DNA的患病率明显高于组2（患病率分别为8 [ 16% ] vs 1 [ 2% ]，P = 0.036，OR：9.3，95%CI：1.1–76.9）。组1的宫颈阴道分泌物中牙龈卟啉单胞菌DNA的患病率明显高于组2（患病率分别为9 [18%]vs1 [ 2% ]，P = 0.02，OR：10.8，95%CI：1.3–88.5）。相反的，牙龈卟啉单胞菌DNA在两组的牙龈下菌斑和唾液样品中均未能检出。结论：目前的研究发现女性生殖道的牙龈卟啉单胞菌感染与复发性流产相关。

The association of arylendosulfatase 1 (SULF1) gene polymorphism with recurrent miscarriage

One of the most common problems in reproductive medicine is recurrent miscarriage (RM). There is increasing evidence showing genetic susceptibility of women is an important risk factor in the occurrence of RM. In recent years, there is a growing interest in sulfate and its role in fetal development. A novel mechanism of SULF1 has been demonstrated for modifying the activities of some growth factors and signalling molecules that have major roles during embryogenesis. The aim of present study was to evaluate the association of SULF1 gene polymorphism (rs6990375 G > A) in Iranian patients with RM. We established a case-control study of 200 Iranian women: 100 patients with the history of two or more RM as cases and 100 healthy women with at least two cases of successful pregnancy and no history of miscarriage as controls. The polymorphism was examined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The genotypic analysis between case and controls showed significant differences (p-value = 0.000). Allelic analysis showed no significant correlation (Χ2 = 3.36, p-value = 0.066). The heterozygous genetic variant was significantly higher among healthy women (OR = 12.67, 95% CI = 6.47-24.79). Our data showed that rs6990375 polymorphism of SULF1 gene could be among one of the factors related to RM in Iranian women. Further evaluation of this polymorphism may be important and need further studies.

Histidine‐rich glycoprotein gene polymorphism in patients with recurrent miscarriage

Association between the histidine-rich glycoprotein (HRG) C633T single nucleotide polymorphism (SNP) and recurrent miscarriage was investigated in a case-control study. The cases constituted 187 women with recurrent miscarriage that were compared with 395 controls who had delivered a child and had no history of miscarriage. Blood samples were collected from each woman, genomic DNA was extracted and genotyped for the HRG C633T SNP. In the whole study population, the percentage of miscarriage was the same, regardless of genotype (C/C 31.2%, C/T 32.9% and T/T 32.5%). However, an association between homozygous T/T carriers and recurrent miscarriage was detected in a subgroup of women with primary recurrent miscarriage (odds ratio 2.44, 95% CI 1.01-5.92). Our results indicate an important role for the HRG C633T SNP in the occurrence of recurrent miscarriage.