Expression of the imprinted IGF2 and H19 genes in the endometrium of cases with unexplained infertility

Korucuoğlu, Ümit; Bırı, Aydan; Konac, Ece; Alp, Ebru; Onen, Ilke Hacer; İlhan, Mustafa; Türkyılmaz, Esengül; Erdem, Ahmet; Erdem, Mehmet; Menevşe, Sevda

doi:10.1016/j.ejogrb.2009.12.007

Cited by 24 publications

(17 citation statements)

References 27 publications

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“…H19 is an important lncRNA that play roles in the infertility [ 35 ] and multiple cancers such as breast cancer [ 36 , 37 ], cervical cancer [ 38 ], liver cancer [ 39 , 40 ] and bladder cancer [ 41 ]. For example, Korucuoglu et al revealed that H19 expression was lower in the infertility group as compared to the control group (4-fold change, P < 0.0001), and Lottin et al showed that over-expression of H19 transcript is associated with cells exhibiting higher tumorigenic phenotypes and promotes tumor progression.…”

Section: Resultsmentioning

confidence: 99%

LncRNA2Function: a comprehensive resource for functional investigation of human lncRNAs based on RNA-seq data

et al. 2015

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BackgroundThe GENCODE project has collected over 10,000 human long non-coding RNA (lncRNA) genes. However, the vast majority of them remain to be functionally characterized. Computational investigation of potential functions of human lncRNA genes is helpful to guide further experimental studies on lncRNAs.ResultsIn this study, based on expression correlation between lncRNAs and protein-coding genes across 19 human normal tissues, we used the hypergeometric test to functionally annotate a single lncRNA or a set of lncRNAs with significantly enriched functional terms among the protein-coding genes that are significantly co-expressed with the lncRNA(s). The functional terms include all nodes in the Gene Ontology (GO) and 4,380 human biological pathways collected from 12 pathway databases. We successfully mapped 9,625 human lncRNA genes to GO terms and biological pathways, and then developed the first ontology-driven user-friendly web interface named lncRNA2Function, which enables researchers to browse the lncRNAs associated with a specific functional term, the functional terms associated with a specific lncRNA, or to assign functional terms to a set of human lncRNA genes, such as a cluster of co-expressed lncRNAs. The lncRNA2Function is freely available at http://mlg.hit.edu.cn/lncrna2function.ConclusionsThe LncRNA2Function is an important resource for further investigating the functions of a single human lncRNA, or functionally annotating a set of human lncRNAs of interest.

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Section: Resultsmentioning

confidence: 99%

LncRNA2Function: a comprehensive resource for functional investigation of human lncRNAs based on RNA-seq data

et al. 2015

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“…Thus, synthetic PIF`s role on H19 modulation in intrauterine growth restriction models is currently investigated but beyond the scope of this manuscript. Notably, women with unexplained infertility and women with endometriosis show decreased H19 expression in eutopic endometrium suggesting a direct clinical link [50, 51]. …”

Section: Discussionmentioning

confidence: 99%

Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS induced inflammatory response

et al. 2017

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Maternal control of inflammation is essential during pregnancy and an exaggerated response is one of the underlying causes of fetal loss. Inflammatory response is mediated by multiple factors and Toll-like receptors (TLRs) are central. Activation of TLRs results in NALP-3 mediated assembly of apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 into the inflammasome and production of pro-inflammatory cytokines IL-1β and IL-18. Given that preventing measures are lacking, we investigated PreImplantation Factor (PIF) as therapeutic option as PIF modulates Inflammation in pregnancy. Additionally, synthetic PIF (PIF analog) protects against multiple immune disorders. We used a LPS induced murine model of fetal loss and synthetic PIF reduced this fetal loss and increased the embryo weight significantly. We detected increased PIF expression in the placentae after LPS insult. The LPS induced serum and placenta cytokines were abolished by synthetic PIF treatment and importantly synthetic PIF modulated key members of inflammasome complex NALP-3, ASC, and caspase-1 as well. In conclusion our results indicate that synthetic PIF protects against LPS induced fetal loss, likely through modulation of inflammatory response especially the inflammasome complex. Given that synthetic PIF is currently tested in autoimmune diseases of non-pregnant subjects (clinicaltrials.gov, NCT02239562), therapeutic approach during pregnancy can be envisioned.

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“…The H19 gene encodes a 2,600‐nt capped, spliced, and polyadenylated noncoding RNA that is predominantly cytoplasmic (Gabory et al , ; Monnier et al , ). In human and mouse endometrium, H19 is expressed in a menstrual cycle‐dependent fashion, with increased expression during the late proliferative phase, but the physiological significance of this expression is unclear (Ariel et al , ; Adriaenssens et al , ; Tanos et al , ; Korucuoglu et al , ). Endometrial H19 expression is positively regulated by E2 and negatively regulated by progesterone in the mouse (Ivanga et al , ).…”

Section: Introductionmentioning

confidence: 99%

“…Unlike Igf1 and Igf1r , which are expressed in both the epithelial and stromal compartments (Tang et al , ), H19 expression is confined to the endometrial stroma (Ariel et al , ; Tanos et al , ). It has been recently shown that women with unexplained infertility show decreased H19 expression in the eutopic endometrium suggesting a direct clinical link (Korucuoglu et al , ).…”

Section: Introductionmentioning

confidence: 99%

H19 lnc RNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis

et al. 2015

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Endometriosis affects approximately 15% of reproductive aged women and is associated with chronic pelvic pain and infertility. However, the molecular mechanisms by which endometriosis impacts fertility are poorly understood. The developmentally regulated, imprinted H19 long noncoding RNA (lncRNA) functions to reduce the bioavailability of microRNA let-7 by acting as a molecular sponge. Here we report that H19 expression is significantly decreased in the eutopic endometrium of women with endometriosis as compared to normal controls. We show that decreased H19 increases let-7 activity, which in turn inhibits Igf1r expression at the post-transcriptional level, thereby contributing to reduced proliferation of endometrial stromal cells. We propose that perturbation of this newly identified H19/Let-7/IGF1R regulatory pathway may contribute to impaired endometrial preparation and receptivity for pregnancy in women with endometriosis. Our finding represents the first example of a lncRNA-based mechanism in endometriosis and its associated infertility, thus holding potential in the development of novel therapeutics for women with endometriosis and infertility.

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Expression of the imprinted IGF2 and H19 genes in the endometrium of cases with unexplained infertility

Cited by 24 publications

References 27 publications

LncRNA2Function: a comprehensive resource for functional investigation of human lncRNAs based on RNA-seq data

LncRNA2Function: a comprehensive resource for functional investigation of human lncRNAs based on RNA-seq data

Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS induced inflammatory response

H19 lnc RNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis

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