Sirtuin 1 Levels in Recurrent Implantation Failure

Üstün, Yaprak Engin; Özgü-Erdinç, A. Seval; Çağlayan, Emel Kıyak; Gülerman, Cavidan; Sarıkaya, Esma; Aktulay, Ayla; Demirtaş, Canan; Erkaya, Salım; Yılmaz, Canan

doi:10.1055/s-0037-1606349

Cited by 5 publications

(3 citation statements)

References 22 publications

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“…While LPS and the inflammatory cytokines TNF-α and IL-1β negatively regulate the mRNA expression of SIRT1, SIRT2 expression level may be regulated by a mechanism independent of inflammation in the human placenta [20]. Women suffering from recurrent implantation failure (RIF) are reported to have higher levels of SIRT1 in their serum as compared to non-pregnant women and healthy pregnant women; however, it should be mentioned that this report may show poor reproducibility due to the low number of subjects [87]. Importantly, the expression patterns of local and systemic cytokines are markedly changed in patients with RIF.…”

Section: Correlation Between Proinflammatory Cytokines and Sirtuin Le...mentioning

confidence: 86%

Sirtuins: Subtle Regulators Involved in Convoluted Mechanisms of Pregnancy

Kahmini

Ghaleh

Shahgaldi

2022

Cell Physiol Biochem

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Sirtuins are Class III protein deacetylases with seven conserved isoforms. In general, Sirtuins are highly activated in starving cells in response to stringent conditions, in which levels of NAD+ are increased. Each member of the Sirtuin family is prominently involved in the regulation of myriad fundamental biological processes including inflammation, proliferation, cell survival, DNA repair and metabolism. Sirtuins can also interact with various signaling pathways and factors such as hypoxia-inducible factors (HIFs), mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB) and the Notch pathway, yet these interactions are demonstrated to be rather complicated. Therefore, deficiency in each member of the Sirtuin family results in severe developmental defects and irregularities both in animals and humans. Currently, a rapidly expanding body of evidence supports that Sirtuins can improve the pregnancy outcome. In fact, each Sirtuin isoform plays distinct yet fundamental roles in controlling folliculogenesis, oocyte meiotic maturation, oocyte aging, trophoblast functions, feto-maternal inflammation and placental angiogenesis and oxidative stress. Consequently, alterations in Sirtuin levels can be a pivotal intermediary step in the pathogenesis of several pregnancy disorders such as fetal growth retardation, preeclampsia and the HELLP syndrome. Furthermore, Sirtuins also appear to be involved in the regulation of parturition and pregnancy complications caused by maternal obesity and diabetes. In this review, we shall first address Sirtuin regulation and functions including their interactions with the most important signaling pathways involved in pregnancy. Then, we will focus on the pivotal roles of Sirtuins in female reproductive functions, normal pregnancy, parturition and pregnancy complications.

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Section: Correlation Between Proinflammatory Cytokines and Sirtuin Le...mentioning

confidence: 86%

Sirtuins: Subtle Regulators Involved in Convoluted Mechanisms of Pregnancy

Kahmini

Ghaleh

Shahgaldi

2022

Cell Physiol Biochem

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“…McBurney et al (2003) found for the first time that SIRT1 null mice are characterized with thin-walled uterus, suggesting that SIRT1 might play an important role in endometrial functions. A study showed RIF patients have higher SIRT1 levels than healthy pregnant women in serum during the 1st to 3rd days of the menstrual cycle, but no statistical significance (Engin-Ustun et al, 2017). However, the abundance of SIRT1 might be different between serum and local endometrial concentrations.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients

Jia

Yao

et al. 2021

Front. Cell Dev. Biol.

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Decidualization is driven by differentiation of human endometrial stromal cells (ESCs), and is a prerequisite for successful implantation and establishment of pregnancy. The critical role of impaired decidualization in women suffered recurrent implantation failure (RIF) has been established, while the underlying mechanism is poorly understood. In the present study, we verified the essential role of Sirtuin1 (SIRT1) in regulating differentiation and maintaining reactive oxygen species (ROS) homeostasis of human ESCs during decidualization. The abundance of SIRT1 was decreased in RIF patients both in the endometria during window of implantation phase and in the decidualized ESCs. Downregulation of SIRT1 disrupted the intracellular ROS homeostasis during decidualization of ESC, manifested as the accumulation of intracellular ROS level and the reduction of antioxidant stress molecules. Elimination of ROS with N-acetyl-L-cysteine (NAC) could rescued the decidualization inhibition caused by SIRT1 knockdown. Further, we explored the insufficient expression of SIRT1 in ESC affected the deacetylation of forkhead box O1 (FOXO1), and thus inhibited the transcriptional activity of FOXO1. This could account for the dysregulation of intracellular ROS homeostasis during decidualization and decreased expression of decidual markers. Collectively, our findings provided insight into the role of down-regulated SIRT1 in the poor decidual response of ESCs in RIF patients.

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“…For example, sirtuin 1 ( SIRT1 ), a gene that plays a crucial role in necroptosis, has been reported to be significantly upregulated in RIF. [ 7 – 9 ] Additionally, levels of cell-derived microparticles (cMPs), released during cell activation or apoptosis, are found to increase significantly in RIF patients. [ 10 ] Moreover, trophoblast necroptosis plays a complex role in pregnancy disorders such as preeclampsia [ 11 , 12 ] and recurrent abortion.…”

Section: Introductionmentioning

confidence: 99%

Necroptosis in recurrent implantation failure: A bioinformatics analysis of key genes and therapeutic targets

Xing,

Ni,

Wang

et al. 2024

Medicine

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Recurrent implantation failure (RIF), a major issue in assisted reproductive technology (ART), may be influenced by necroptosis, a form of cell death linked to several diseases. This study was aimed at investigating the involvement of necroptosis in RIF. Using RNA-sequencing data from the Gene Expression Omnibus database, we identified differentially expressed necroptosis-related genes (DENRGs) in RIF patients compared with those in controls. Functional enrichment, protein–protein interaction (PPI) networks, and transcription factor (TF) regulatory networks were analyzed to identify key genes. Immune cell infiltration was analyzed using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Finally, potential therapeutic drugs targeting key genes were explored using a Drug Gene Interaction Database. In total, 20 DENRGs associated with RIF were identified, with a focus on 6 key genes (MLKL, FASLG, XIAP, CASP1, BIRC3, and TLR3) implicated in necroptosis and immune processes. These genes were used to develop a predictive model for RIF, which was validated in 2 datasets. The model and TF network analysis underscored the importance of TLR3. Immune infiltration analysis showed reduced levels of 16 immune cells in RIF patients, highlighting immune system alterations. Several drugs targeting CASP1, such as nivocasan and emricasan, were identified as potential treatments. The study sheds light on the role of necroptosis in RIF, identifying key genes and immune alterations that could serve as biomarkers and therapeutic targets. These findings pave the way for future experimental research and clinical applications targeting necroptosis in RIF treatment.

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Sirtuin 1 Levels in Recurrent Implantation Failure

Cited by 5 publications

References 22 publications

Sirtuins: Subtle Regulators Involved in Convoluted Mechanisms of Pregnancy

Sirtuins: Subtle Regulators Involved in Convoluted Mechanisms of Pregnancy

Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients

Necroptosis in recurrent implantation failure: A bioinformatics analysis of key genes and therapeutic targets

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