Simvastatin and uterine fibroids: opportunity for a novel therapeutic option

Ali, Mohamed; Jackson-Bey, Tia; Al-Hendy, Ayman

doi:10.1016/j.fertnstert.2018.08.043

Cited by 2 publications

(2 citation statements)

References 5 publications

(7 reference statements)

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“…Progesterone is a necessary hormone for pregnancy, and its supplementation can prevent recurrent miscarriage and reduce implantation failure in IVT cycles (Nardo and Sallam, 2006). Simvastatin, a lipid regulating agent, also shows impact on polycystic ovary syndrome (PCOS), endometriosis and uterine fibrosis (Banaszewska et al, 2011;Taylor et al, 2017;Ali et al, 2018). Simvastatin has been reported to reduce the expression of neopterin in endometriosis, which is a marker of inflammation and immune system activation (Taylor et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Simvastatin has been reported to reduce the expression of neopterin in endometriosis, which is a marker of inflammation and immune system activation (Taylor et al, 2017). Simvastatin can also inhibit C-reactive protein in PCOS and suppress fibroid proliferation and extracellular matrix production in uterine fibrosis (Banaszewska et al, 2011;Ali et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Gene profiling reveals the role of inflammation, abnormal uterine muscle contraction and vascularity in recurrent implantation failure

Dong

Zhou²,

Li³

et al. 2023

Front. Genet.

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Objective: Recurrent implantation failure (RIF) is now disturbing numerous infertile couples accepting assisted reproductive technology (ART). And the endometrial factors are crucial causes of recurrent implantation failure. However, its mechanism is still unclear. Thus, the aim of this study is to identify altered biologic processes in endometrium that may contribute to recurrent implantation failure.Methods: We recruited two microarray datasets (GSE103465, GSE111974) from Gene Expression Omnibus database (GEO), which contain endometrium from RIF and normal women during implantation period. Using the online tools GEO2R and Venny, we identified Differentially Expressed Genes (DEGs) of selected datasets, and obtained common DEGs. Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCatar pathway enrichment were conducted with Enrichr platform, “ssgsea” and “ggplot2” package of RStudio. PPI networks and hub gene related TF-gene interaction and TF-miRNA co-regulation networks were built via online tools STRING and NetworkAnalyst. Immune infiltration analysis was performed by CIBERSORT platform. Recurrent implantation failure subgroup identification was achieved through “ConsensusClusterPlus,” “tsne,” “ssgsea”, and “ggpubr” package in RStudio. Diagnostic characteristic ROC curves were constructed via “pROC” and “ggplot2” package of RStudio. Enrichr platform was utilized to find drugs targeting hub genes.Results: 26 common DEGs were confirmed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes/BioCarta analysis determined common DEGs were mainly enriched in inflammation associated pathways including TNF, NF-κB, IL-4, IL-10, IL-6, and TGF-β signaling pathways. Five hub genes (PTGS2, VCAM1, EDNRB, ACTA2, and LIF) and related TF-gene and TF-miRNA interactions were identified. Immune infiltration analysis indicated the importance of macrophage M2 in recurrent implantation failure patients. Importantly, subgroup identification analysis highlighted that recurrent implantation failure patients can be divided into two subgroups with different phenotypes. Moreover, the ROC curves and drugs may provide new diagnostic and therapeutic thought for recurrent implantation failure.

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