Epigenetic clocks provide clues to the mystery of uterine ageing

Human Reproduction Update, Год журнала: 2022, Номер 29(3), С. 259 - 271

Опубликована: Дек. 14, 2022

Abstract BACKGROUND Rising maternal ages and age-related fertility decline are a global challenge for modern reproductive medicine. Clinicians researchers pay specific attention to ovarian ageing hormonal insufficiency in this regard. However, uterine is often left out of the picture, with majority clinicians being close unanimous on absence functional tissues. Therefore, most existing techniques treat an implantation rates based primarily supplementation oocyte donation. Solving issue might lead adjustment these methods. OBJECTIVE AND RATIONALE A focus possibility slowing it emerged development information theory ageing, which identifies genomic instability erosion epigenetic landscape as important drivers functionality cells Age-related smoothing tissue function can be assessed by measuring ticking clocks. Within review, we explore whether uterus experiences alterations using elegant approach. We analyse data clocks endometrium, highlight approaches improve accuracy cycling tissue, speculate endometrial pathologies whose progression predicted altered speed discuss possibilities down SEARCH METHODS Data review were identified searches Medline, PubMed Google Scholar. References from relevant articles search terms ‘ageing’, ‘maternal age’, ‘female reproduction’, ‘uterus’, ‘endometrium’, ‘implantation’, ‘decidualization’, ‘epigenetic clock’, ‘biological ‘DNA methylation’, ‘fertility’ ‘infertility’ selected. total 95 published English between 1985 2022 included, six describe use clock evaluate uterine/endometrium ageing. OUTCOMES Application Horvath DNAm PhenoAge demonstrated poor correlation chronological age endometrium. Several suggested enhance predictive power The first was increase number samples training dataset, Zang clock, or more sophisticated clock-building algorithms, AltumAge clock. second method adjust according dynamic nature Using either approach revealed strong providing solid evidence tissue. Furthermore, acceleration/deceleration, estimated clocks, promising tool predict gain insights into origin various pathologies, including recurrent failure, cancer endometriosis. Finally, there several strategies slow even reverse that applied reduce risk impairments. WIDER IMPLICATIONS factor should considered, along issues, correct female age. Epigenetic tested deeper understanding disorders.

Язык: Английский

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Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice

EBioMedicine, Год журнала: 2023, Номер 88, С. 104433 - 104433

Опубликована: Янв. 7, 2023

Successful embryo implantation requires the attachment of a blastocyst to receptive endometrial epithelium, which was disturbed in women with recurrent failure (RIF). Endometrial β3-integrin most important adhesion molecule contributing receptivity both humans and mice. Nur77 has been proven indispensable for fertility mice, here we explore role on embryo-epithelial potential treatment failure.The expression location Mst1 endometrium from fertile RIF patients were examined by IHC, qRT-PCR Western blotting. In vitro kinase assay following LC-MS/MS used identify phosphorylation site activated Mst1. The phosphorylated detected phos-tag SDS-PAGE specific antibody against phospho-Nur77-Thr366. effect embryo-epithelium interaction determined BeWo spheroid or mouse assay, delayed model. RNA-seq mechanism derived peptide promotes receptivity.Endometrial Mammalian sterile 20 (STE20)-like 1 (Mst1) level decreased than that control group, while activation epithelial cells promoted trophoblast-uterine epithelium adhesion. mediated facilitated active Mechanistically, mst1 transcription activity phosphorylating at threonine 366 (T366), consequently increased downstream target expression. Furthermore, Nur77-derived containing T366 markedly Ishikawa ([4 (2-4)] vs [3 (2-4)]) rate (4 1.4) model regulating integrin signalling. Finally, it is observed phospho-Nur77 (T366) 80% RIF.In addition uncovering regulatory Mst1/Nur77/β3-integrin signal axis involved regulation interaction, our finding provides novel marker therapeutic agent failure.National Key Research Development Program China (2018YFC1004400), National Natural Science Foundation (82171653, 82271698, 82030040, 81971387 30900727), Institutes Health grants (R01HL103869).

Язык: Английский

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Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 10

Опубликована: Янв. 10, 2023

Assisted reproductive techniques as a new regenerative medicine approach have significantly contributed to solving infertility problems that affect approximately 15% of couples worldwide. However, the success rate an in vitro fertilization (IVF) cycle remains only about 20%-30%, and 75% these losses are due implantation failure (the crucial rate-limiting step gestation). Implantation abnormal placenta formation mainly caused by defective adhesion, invasion, angiogenesis. Placental insufficiency endangers both mother's fetus's health. Therefore, we suggested novel treatment strategy improve endometrial receptivity rate. In this strategy, regulating mir-30d expression upstream transcriptomic modifier embryo results modified involved genes embryonic angiogenesis consequently impedes failure. For purpose, "scaffold/matrix attachment regions (S/MARs)" employed non-viral episomal vectors, transfecting into trophoblasts exosome-liposome hybrid carriers. These vectors comprise CRISPR/dCas9 with guide RNA exclusively induce miR-30d gene hypoxic stress conditions. order avoid concerns genetic manipulation, our vector would be transfected specifically trophoblast layer blastocyst via binding Erb-B4 receptors without entering inner cell mass. Additionally, S/MAR do not integrate original DNA. As on/off regulatory switch, hypoxia-sensitive promoter (HRE) is localized dCas9. The increases before during placental conditions extinguished after hypoxia elimination. This hypothesis emphasizes improving uterine microenvironment pregnancy will result increased reduced insufficiency, insight translational medicine.

Язык: Английский

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Mechanisms of Bushen Tiaoxue Granules against controlled ovarian hyperstimulation-induced abnormal morphology of endometrium based on network pharmacology

Journal of Ovarian Research, Год журнала: 2024, Номер 17(1)

Опубликована: Янв. 26, 2024

Abstract Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity reported in our previous study. This study aims to explore mechanisms ameliorating abnormal morphology endometrium based network pharmacology. Active compounds were identified via traditional medicine systems pharmacology and UPLC-MS technology. SwissTargetPrediction platform HERB database screen out putative targets BTG. Potential dysfunction caused by COH obtained from three GEO databases. Through STRING database, protein–protein interaction was carried according cross-common diseases drugs. GO terms KEGG pathways enrichment analyses conducted Metascape database. AutoDock Vina docking validation affinity between active potential targets. Finally, vivo experiments verify derived A total 141 effective ingredients TCMSP nine which verified UPLC-MS. Six genes selected through intersection 534 disease related 165 drug Enrichment showed might reverse regulating adherens junction arachidonic acid metabolism. Hematoxylin–eosin staining revealed ameliorated loose edematous status epithelium COH. protein expression FOXO1A, β-Catenin COX-2 decreased group, up-regulated significantly alleviates edema may be adheren junctions activation quercetin, taxifolin, kaempferol, eriodictyol, isorhamnetin exhibit marginal cytotoxicity. Both high low concentrations taxifolin are capable effectively hESC cellular activity.

Язык: Английский

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The use of the chorioallantoic membrane as an experimental model for studying markers of endometrial receptivity

Medicine and ecology, Год журнала: 2025, Номер 4, С. 43 - 52

Опубликована: Янв. 21, 2025

The article presents a review of articles aimed at summarizing the results studies using choriollantoic membrane (СAM) to study markers and mechanisms endometrial receptivity angiogenesis. Considering these together clarifies complex regulatory networks involved in vascular development susceptibility. Understanding intricacies angiogenesis susceptibility is crucial reproductive medicine infertility treatment. chorioallantoic (CAM) its analogues, angiogenic model derived from stroma (CAM), offer valuable platforms for such research. A comprehensive search scientific literature databases was conducted identify relevant CAM. Studies CAM have provided insight into susceptibility, shedding light on structural changes associated with development. Similarly, information pinopods other indicating potential clinical applications medicine. Together, contribute deeper understanding cellular molecular regulation. They emphasize role various factors, including growth cytokines, signaling pathways, inducing modulating Such findings can serve as basis new diagnostic therapeutic strategies

Язык: Английский

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Uterine Microbiota and Bisphenols: Novel Influencers in Reproductive Health

Journal of Xenobiotics, Год журнала: 2025, Номер 15(1), С. 26 - 26

Опубликована: Фев. 2, 2025

Infertility affects 8–12% of couples worldwide, and 30–75% preclinical pregnancy losses are due to a failure during the implantation process. Exposure endocrine disruptors, like bisphenols, among others, has been associated with increase in infertility observed past decades. An correlated exposure disruptors bisphenols. The uterus harbors its own microbiota, changes this microbiota have linked several gynecological conditions, including reproductive failure. There no studies on effects bisphenols uterine–microbiota composition, but some inferences can be gleaned by looking at gut. Bisphenols alter gut molecular mechanism which regulates intestinal permeability involves Toll-like receptors (TLRs) tight junction (TJ) proteins. TJs participate embryo uterus, bisphenol disrupts expression localization TJ aim review is summarize current knowledge female tract (FRT), association different diseases—particularly failure—the composition health, mechanisms regulating interactions crucial for implantation. This also highlights existing gaps outlines research needs future risk assessments regarding reproduction.

Язык: Английский

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Identifying Shared Molecular Landscape between Uterine Fibroids and Recurrent Implantation Failure: An Integrated Bioinformatics Study

Heliyon, Год журнала: 2025, Номер unknown, С. e43006 - e43006

Опубликована: Фев. 1, 2025

Язык: Английский

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Live birth rate and perinatal outcomes following sequential embryo transfer in women with recurrent implantation failure undergoing frozen-thawed embryo transfer cycles

BMC Pregnancy and Childbirth, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 11, 2025

Язык: Английский

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Enhanced Endometrial Receptivity via Epigallocatechin Gallate (EGCG)-Loaded Menstrual Blood-Derived Exosomes

Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер unknown, С. 103801 - 103801

Опубликована: Апрель 1, 2025

Язык: Английский

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Bibliometric analysis of the links between embryo transfer and endometrial receptivity: Mapping knowledge landscapes and emerging trends (2005–2024)

Medicine, Год журнала: 2025, Номер 104(17), С. e42014 - e42014

Опубликована: Апрель 25, 2025

Background: Infertility is a significant global reproductive health challenge with varying prevalence across regions. While assisted technologies, especially in vitro fertilization, have created new possibilities for treating infertility, embryo transfer success remains limited by multiple factors, particularly endometrial receptivity. Understanding the relationship between and receptivity crucial advancing medicine improving infertility treatment outcomes. To address lack of bibliometric analysis this field, we conducted comprehensive study relevant academic literature. Methods: We analyzed articles reviews on from Web Science Core Collection using CiteSpace, VOSviewer, Bibliometrix package. The focused countries, institutions, journals, authors, keywords, references. Results: identified 1478 documents published over 2 decades, showing an upward trend annual publications. China led publication volume, while USA had highest citation impact. University Valencia Shanghai Jiao Tong were most productive fertility sterility being leading journal. Simón, C emerged as influential author based count citations. Key research areas included comparing fresh versus frozen transfer, addressing repeated implantation failure, array personalized represents emerging direction medicine. Conclusion: This first provides valuable insights into knowledge development, hotspots, future directions serving reference scholars

Язык: Английский

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