Preeclampsia (PE) is a disorder affecting 2–10% of pregnancies and has a major role for perinatal and maternal mortality and morbidity. PE can be occurred by initiation of new hypertension combined with proteinuria after 20 weeks gestation, as well as various reasons such as inflammatory cytokines, poor trophoblast invasion can be related with PE disease. Environmental factors can cause epigenetic changes including DNA methylation, microRNAs (miRNAs), and histone modification that may be related to different diseases such as PE. Abnormal DNA methylation during placentation is the most important epigenetic factor correlated with PE. Moreover, changes in histone modification like acetylation and also the effect of overregulation or low regulation of miRNAs or long noncoding RNAs on variety signaling pathways can be resulted in PE. The aim of this review is to describe of studies about epigenetic changes in PE and its therapeutic strategies.

Recurrent pregnancy loss (RPL) is a one of the most common obstetrical complications. Since, the successful pregnancy occurs in T helper 2 (Th2)‐dominant situation and since, Th1 type immunity is related to pregnancy failure, we investigated the effects of cyclosporine on Th1 and Th2 cells in RPL women. Totally, 76 RPL patients (38 women as treated group and 38 as control group) were included in this study. Flow cytometry was utilized to analyze the frequency of Th1 and Th2 in blood samples. Also, real‐time polymerase chain reaction was carried out to assess the messenger RNA (mRNA) expression of transcription factors and enzyme‐linked immunosorbent assay was used to evaluate Th1 and Th2 related cytokines. Significant decrease in Th1 frequency (p = 0.0004), Th1/Th2 ratio (p < 0.0001), T‐bet mRNA expression (p < 0.0001), interferon‐γ (p = 0.0007), and tumor necrosis factor α (p = 0.0002) secretion level were observed in cyclosporine group. Moreover, significant increase in Th2 frequency (p < 0.0001), mRNA expression of GATA binding protein 3 (p = 0.0001), and interleukin 10 secretion level (p = 0.0027) was also evident in treated group. At the end of the investigation, 31 (81.5%) patients in cyclosporine‐treated group had successful childbirth when compared with 16 (42.1%) women in control group (p = 0.0001). Given this, cyclosporine treatment for RPL patients with elevated Th1/Th2 ratio can result in improved pregnancy outcome.

ProblemIncreased oxidative stress (OS) and inflammatory factors in metabolic syndrome (MS) patients are considered as risk factors for recurrent implantation failure (RIF). The aim of this study was to investigate OS markers, inflammatory factors, related microRNAs (miRNA) expression, and cytokine and transcription factors RNA expression.Method of studyWe evaluated the frequency of helper T (Th) 17 and regulatory T (Treg) cells in recurrent implantation failure (RIF) women with or without MS. miRNA expression, an inflammatory cytokine, and transcription factors were measured by real‐time PCR. The level of interleukin (IL)‐1β, IL‐6, IL‐17, tumour necrosis factor‐alpha (TNF‐alpha) and chemokine (C‐C motif) ligand 2 (CCL‐2), and C‐X‐C motif chemokine ligand 8 (CXCL‐8) were measured by enzyme‐linked immunosorbent assay (ELISA). OS markers were evaluated by spectrophotometric assay. Th17 and Treg cell frequencies were determined by flow cytometry.ResultsThe expression of AP1, NF‐κB, FOXP3, miRNA‐21; serum or plasma level of OS markers (ie, nitric oxide, total oxidant status, and myeloperoxidase); serum level of inflammatory factors (ie, IL1‐β, IL‐6, IL‐17, TNF‐alpha, CXCL‐8, and CCL‐2); and frequency of Th17 cells were increased in RIF‐MS patients in comparison with RIF women without MS (RIF‐NMS) and control group. The expression of miRNA‐223 and 146a, antioxidant enzymes, namely superoxide dismutase (SOD) and catalase (CAT), and frequency of Treg also declined in RIF‐MS patients.ConclusionOverall, our findings suggest that MS in RIF patients causes increased inflammatory factors and OS, which in turn leads to implantation failure.

ProblemTo investigate whether metabolic syndrome (MetS) is associated with exacerbation of inflammatory responses in preeclamptic (PE) patients, the dynamic changes of Th17 and Treg cells, monocytes, cytokines, and transcription pattern of inflammasome‐related genes were analyzed in 35 women with PE suffering from MetS in comparison to 38 PE women without MetS and healthy pregnant women.Method of studyExpression of inflammasome‐related genes, cytokines, and also TLR4 was measured using real‐time PCR. Serum and medium supernatant cytokines levels of PBMCs and serum levels of HMGB1 and Caspase‐1 were also evaluated by ELISA. Monocytes, Th17, and Treg cells frequency were also determined by flow cytometry.ResultPE women with MetS exhibited increased percentage of non‐classical and intermediate monocytes and Th17 cells (P = 0.025). Furthermore, decreased Treg cells frequency was also observed in PE women with MetS compared to PE women (P = 0.019). The mRNA expression of inflammasome‐related genes (Caspase‐1, NLRP3, HMGB1), TLR4, IL‐1β, IL‐6, IL‐17, IL‐18, and TNF‐α was significantly higher in PE patients with MetS than that of the healthy pregnant individuals (P < 0.0001) and PE patients (P < 0.0001). Serum levels of TGF‐β and TNF‐α in PE patients with MetS were increased compared to other two groups, while IL‐10 levels were significantly reduced. A significant sFlt (P = 0.016), Caspase‐1 (P = 0.012), HMGB1 (P = 0.016) upregulation, and VEGF (P = 0.023) downregulation were also observed in the serum of PE women having MetS compared to PE women.ConclusionMetS is closely related to the exacerbation of inflammatory reactions in PE. This study indicates that, in order to diminish the systemic features of PE, prior to conceive and start a pregnancy, MetS should be severely considered and managed.

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