Association of oxidative stress-related genes with idiopathic recurrent miscarriage

Khadzhieva, Maryam B.; Lutcenko, N. N.; Volodin, I.V.; Morozova, K. V.; Salnikova, Lyubov E.

doi:10.3109/10715762.2014.891735

Cited by 26 publications

(17 citation statements)

References 45 publications

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“…3a). Among them the genes ATF4 1617, C3 1819 , PHLDA2 20, GPX4 21 and ICAM1 22 have been previously linked with the pathogenesis of pregnancy loss. Additionally, GPX4 has been implicated in preeclampsia23, PHLDA2 242526 and SLC16A2 2728 in fetal growth restriction, CD74 and LAPTM5 in preterm premature rupture of membranes29 (details and full list of references in Supplementary Data S3b).…”

Section: Resultsmentioning

confidence: 99%

RNA sequencing of chorionic villi from recurrent pregnancy loss patients reveals impaired function of basic nuclear and cellular machinery

Sõber

Rull

Reiman

et al. 2016

Sci Rep

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Recurrent pregnancy loss (RPL) concerns ~3% of couples aiming at childbirth. In the current study, transcriptomes and miRNomes of 1st trimester placental chorionic villi were analysed for 2 RPL cases (≥6 miscarriages) and normal, but electively terminated pregnancies (ETP; n = 8). Sequencing was performed on Illumina HiSeq 2000 platform. Differential expression analyses detected 51 (27%) transcripts with increased and 138 (73%) with decreased expression in RPL compared to ETP (DESeq: FDR P < 0.1 and DESeq2: <0.05). RPL samples had substantially decreased transcript levels of histones, regulatory RNAs and genes involved in telomere, spliceosome, ribosomal, mitochondrial and intra-cellular signalling functions. Downregulated expression of HIST1H1B and HIST1H4A (Wilcoxon test, fc≤0.372, P≤9.37 × 10−4) was validated in an extended sample by quantitative PCR (RPL, n = 14; ETP, n = 24). Several upregulated genes are linked to placental function and pregnancy complications: ATF4, C3, PHLDA2, GPX4, ICAM1, SLC16A2. Analysis of the miRNA-Seq dataset identified no large disturbances in RPL samples. Notably, nearly 2/3 of differentially expressed genes have binding sites for E2F transcription factors, coordinating mammalian endocycle and placental development. For a conceptus destined to miscarriage, the E2F TF-family represents a potential key coordinator in reprogramming the placental genome towards gradually stopping the maintenance of basic nuclear and cellular functions.

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Section: Resultsmentioning

confidence: 99%

RNA sequencing of chorionic villi from recurrent pregnancy loss patients reveals impaired function of basic nuclear and cellular machinery

Sõber

Rull

Reiman

et al. 2016

Sci Rep

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“…The accumulation of ROS including H 2 O 2 , lipid peroxides and GSSG, as well as the drop in GSH/GSSG ratios, all illustrated in this study clearly indicate prevalence of enhanced OS that could have caused toxicity and alteration in the expression of genes related to antioxidants and apoptosis in RM patients thus leading to miscarriage. In a recent study, the association of polymorphism in OS-related genes with idiopathic RM has been reported ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Biochemical Markers of Oxidative Stress in Saudi Women with Recurrent Miscarriage

Ghneim

Alshebly

2016

J Korean Med Sci

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This study was undertaken to investigate the antioxidant/oxidant status in recurrent miscarriage patients. Antioxidants including glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), reduced glutathione (GSH) and selenium (Se), as well as the oxidants hydrogen peroxide (H2O2), oxidised glutathione (GSSG) and lipid peroxidation were assayed in plasma, whole blood and placental tissue of non-pregnant women (NP), healthy pregnant women (HP), and recurrent miscarriage (RM) patients. Results indicated that all antioxidant activities and levels in plasma and whole blood of HP women were consistently moderately lower, and much more significantly lower in RM patients when both were compared to those seen in NP women (P<0.05 and P<0.001, respectively). Furthermore, whereas plasma antioxidant activities and levels were significantly lower in RM patients, those of whole blood and placental tissue were much more significantly lower when compared with HP women (P<0.001). Concurrent with these findings there were consistent increases of equal statistical significance and magnitude in the levels of all investigated oxidants assayed in all samples when compared in between subjects of the study as indicated above. Data thus illustrated a distinct shift in favor of oxidative reactions and reactive oxygen species (ROS) generation, and very significant decreases in the GSH/GSSG ratios in whole blood and placental tissue of RM patients when compared to HP and NP women (P<0.001). The above noted oxidative stress could have been a major causative factor of recurrent miscarriage.

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“…Single nucleotide polymorphisms of genes associated with oxygen free radical metabolism, ABCB1, COMT, GPX4, and OGG1, have been reported to lead to a doubling of the risk of recurrent miscarriage (177). In addition, polymorphism of genes that regulate the complement cascade, such as membrane cofactor protein and C4 binding protein, have a putative role in recurrent early pregnancy loss (353).…”

Section: Genetic Polymorphismsmentioning

confidence: 99%

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

Hart

2016

Physiological Reviews

174

119

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Across the Western World there is an increasing trend to postpone childbearing. Consequently, the negative influence of age on oocyte quality may lead to a difficulty in conceiving for many couples. Furthermore, lifestyle factors may exacerbate a couple's difficulty in conceiving due mainly to the metabolic influence of obesity; however, the negative impacts of low peripheral body fat, excessive exercise, the increasing prevalence of sexually transmitted diseases, and smoking all have significant negative effects on fertility. Other factors that impede conception are the perceived increasing prevalence of the polycystic ovary syndrome, which is further exacerbated by obesity, and the presence of uterine fibroids and endometriosis (a progressive pelvic inflammatory disorder) which are more prevalent in older women. A tendency for an earlier sexual debut and to have more sexual partners has led to an increase in sexually transmitted diseases. In addition, there are several genetic influences that may limit the number of oocytes within the ovary; consequently, by postponing attempts at childbearing, a limitation of oocyte number may become evident, whereas in previous generations with earlier conception this potentially reduced reproductive life span did not manifest in infertility. Environmental influences on reproduction are under increasing scrutiny. Although firm evidence is lacking however, dioxin exposure may be linked to endometriosis, phthalate exposure may influence ovarian reserve, and bisphenol A may interfere with oocyte development and maturation. However, chemotherapy or radiotherapy is recognized to lead to ovarian damage and predispose the woman to ovarian failure.

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Association of oxidative stress-related genes with idiopathic recurrent miscarriage

Cited by 26 publications

References 45 publications

RNA sequencing of chorionic villi from recurrent pregnancy loss patients reveals impaired function of basic nuclear and cellular machinery

RNA sequencing of chorionic villi from recurrent pregnancy loss patients reveals impaired function of basic nuclear and cellular machinery

Biochemical Markers of Oxidative Stress in Saudi Women with Recurrent Miscarriage

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

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