Expression of Pinopodes in the Endometrium from Recurrent Pregnancy Loss Women. Role of Thrombomodulin and Ezrin

D’Ippolito, Silvia; Nicuolo, Fiorella Di; Papi, Massimiliano; Castellani, Roberta; Palmieri, Valentina; Masciullo, Valeria; Arena, Vincenzo; Tersigni, Chiara; Bernabei, Micaela; Pontecorvi, Alfredo; Scambia, Giovanni; Simone, Nicoletta Di

doi:10.3390/jcm9082634

Cited by 17 publications

(16 citation statements)

References 49 publications

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“…Pinopodes seem to be a useful maker for endometrium receptivity in many species 33,34 . In this study, the SEM observation showed that the number of pinopodes was significantly different between agomir NC group and miR‐100‐5p agomir group.…”

Section: Discussionmentioning

confidence: 48%

“…32 Our study also verified that overexpressed circ-9110 promoted ESCs Pinopodes seem to be a useful maker for endometrium receptivity in many species. 33,34 In this study, the SEM observation showed that the number of pinopodes was significantly different between agomir NC group and miR-100-5p agomir group. The number of pinopodes and length of microvilli in miR-100-5p agomir group significantly decreased compared with agomir NC group.…”

Section: Con Clus Ionmentioning

confidence: 52%

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Effect of MiR‐100‐5p on proliferation and apoptosis of goat endometrial stromal cell in vitro and embryo implantation in vivo

Zhang

Cao

et al. 2022

J Cellular Molecular Medi

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The growth of endometrial stromal cells (ESCs) at implantation sites may be a potential factor affecting the success rate of embryo implantation. Incremental proofs demonstrated that ncRNAs (e.g. miRNAs, lncRNAs and circRNAs) were involved in various biological procedures, including proliferation and apoptosis. In this study, the role of miR‐100‐5p on proliferation and apoptosis of goat ESCs in vitro and embryo implantation in vivo was determined. The mRNA expression of miR‐100‐5p was significantly inhibited in the receptive phase (RE) rather than in the pre‐receptive phase (PE). Overexpression of miR‐100‐5p suppressed ESCs proliferation and induced apoptosis. The molecular target of MiR‐100‐5p, HOXA1, was confirmed by 3′‐UTR assays. Meanwhile, the product of HOXA1 mRNA RT‐PCR increased in the RE more than that in the PE. The HOXA1‐siRNA exerted significant negative effects on growth arrest. Instead, incubation of ESCs with miR‐100‐5p inhibitor or overexpressed HOXA1 promoted the cell proliferation. In addition, Circ‐9110 which acted as a sponge for miR‐100‐5p reversed the relevant biological effects of miR‐100‐5p. The intrinsic apoptosis pathway was suppressed in ESCs, revealing a crosstalk between Circ‐9110/miR‐100‐5p/HOXA1 axis, PI3K/AKT/mTOR, and ERK1/2 pathways. To further evaluate the progress in study on embryo implantation regulating mechanism of miR‐100‐5p in vivo, the pinopodes of two phases were observed and analysed, suggesting that, as similar as in situ, miR‐100‐5p was involved in significantly regulating embryo implantation in vivo. Mechanistically, miR‐100‐5p performed its embryo implantation function through regulation of PI3K/AKT/mTOR and ERK1/2 pathways by targeting Circ‐9110/miR‐100‐5p/HOXA1 axis in vivo.

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Section: Discussionmentioning

confidence: 48%

Section: Con Clus Ionmentioning

confidence: 52%

Effect of MiR‐100‐5p on proliferation and apoptosis of goat endometrial stromal cell in vitro and embryo implantation in vivo

Zhang

Cao

et al. 2022

J Cellular Molecular Medi

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“…Although previously controversial, recent literature has deemed the presence of pinopodes in the endometrial epithelia as a credible biomarker of uterine receptivity [52, 54]. Filamentous actin expression coincides with pinopode formation during receptivity on the apical surface of luminal epithelial cells [55]. In the endometria of from those suffering recurrent pregnancy loss, both ezrin and thrombomodulins were downregulated which disrupted the organisation of cytoskeletal actin filaments and may ultimately impaired pinopode formation.…”

Section: Discussionmentioning

confidence: 99%

Insulin exposed endometrial epithelial cells cultured in a microfluidic device alters transcripts involved in translation that may contribute to reduced implantation capacity of the endometrium

Baik

Tinning

Wang

et al. 2021

Preprint

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Obesity is a rapidly growing public health issue among women of reproductive age. It is also associated with decreased reproductive function including implantation failure. Implantation failure can result from a myriad of factors including impaired gametes and endometrial dysfunction. The mechanisms of how obesity-related hyperinsulinaemia disrupts endometrial function and implantation are poorly understood. Our study aims to investigate potential mechanisms by which insulin alters endometrial transcript expression, which may affect endometrial receptivity. Ishikawa cells mimicking human endometrial epithelium were seeded into a microfluidics organ-on-chip device to produce an in vitro endometrium. Syringe pump was attached to the microfluidics device to deliver three varying treatments into Ishikawa cells: 1) media control 2) vehicle control (PBS acidified to pH3 with acetic acid) 3) Insulin (2mg/mL) at a constant flow rate of 1uL/min for 24 hours to mimic secretion in vivo. Three biological replicates were obtained. Insulin-induced transcriptomic response of the in vitro endometrium was quantified via RNA sequencing, and subsequently analysed using DAVID and Webgestalt to identify Gene Ontology (GO) terms and signalling pathways. A Total of 29 transcripts showed differential expression levels across two comparison groups (control v vehicle control; vehicle control v insulin). There were nine transcripts significantly differentially expressed in vehicle control v insulin group (p<0.05). Functional annotation analysis of transcripts altered by insulin (n=9) identified three significantly enriched GO terms: SRP-dependent cotranslational protein targeting to membrane, poly(A) binding, and RNA binding (p<0.05). Over-representation analysis found three significantly enriched signalling pathways relating to insulin-induced transcriptomic response: protein export, glutathione metabolism, and ribosome pathways (p<0.05). Insulin-induced dysregulation of biological functions and pathways highlight potential mechanisms by which high insulin concentrations within maternal circulation may perturb endometrial receptivity.

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“…In the initial stage of pregnancy, TM is involved in embryonic implantation by maintaining the cytoskeletal organization of endometrial cells. 57 TM is identified on the endometrium, which is modified into decidua during placentation. Endometrial TM connects to actin filaments via bridging protein ezrin, which is responsible for cell-to-cell adhesion and cytoskeletal development.…”

Section: Function Of Tm During Pregnancymentioning

confidence: 99%

Thrombomodulin and pregnancy in the limelight: Insights into the therapeutic aspect of thrombomodulin in pregnancy complications

Oda

Nagamatsu

Osuga

2022

Journal of Thrombosis and Haemostasis

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Background Thrombomodulin (TM) is a transmembrane glycoprotein expressed on the endothelial cell functioning as a cofactor in the anticoagulation system. However, aside from anticoagulation, recent studies have revealed its multiple organ protective roles such as anti‐inflammation, angiogenesis, and cell proliferation, which may redefine the function of TM. Although TM is predominantly expressed on placental trophoblasts, the physiological role of TM during pregnancy remains unclear. Because the understanding of TM function has drastically progressed, these new discoveries shed light on the unknown activities of placental TM. Moreover, the clinical application of recombinant TM (rTM) has opened the possibility of TM as a therapeutic target for pregnancy complications. Objectives Here, we comprehensively review the studies elucidating the role of TM during pregnancy from both classic and newly discovered perspectives, and seek for its potential as a therapeutic target for pregnancy complications. Methods Basic research using trophoblast cells and transgenic mice, as well as cohort studies of inherited TM deficiency and clinical trials of rTM were summarized, which led us to further discuss the clinical application of rTM as a novel therapeutic for pregnancy complications. Results and Conclusion Accumulating evidence suggest the relevance of placental TM deficiency in pregnancy complications such as miscarriage, fetal growth restriction, and preeclampsia. Most importantly, promising results in animal studies and clinical trials further assure the possibility of rTM as an optimal therapeutic for such conditions. The therapeutic potential of TM raised throughout this review could drastically change the clinical approach to pregnancy complication and improve maternal outcomes.

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Expression of Pinopodes in the Endometrium from Recurrent Pregnancy Loss Women. Role of Thrombomodulin and Ezrin

Cited by 17 publications

References 49 publications

Effect of MiR‐100‐5p on proliferation and apoptosis of goat endometrial stromal cell in vitro and embryo implantation in vivo

Effect of MiR‐100‐5p on proliferation and apoptosis of goat endometrial stromal cell in vitro and embryo implantation in vivo

Insulin exposed endometrial epithelial cells cultured in a microfluidic device alters transcripts involved in translation that may contribute to reduced implantation capacity of the endometrium

Thrombomodulin and pregnancy in the limelight: Insights into the therapeutic aspect of thrombomodulin in pregnancy complications

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