Endometriosis: Etiology, pathobiology, and therapeutic prospects

Cell, Journal Year: 2021, Volume and Issue: 184(11), P. 2807 - 2824

Published: May 1, 2021

Language: Английский

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Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(12), P. 1698 - 1711

Published: Dec. 1, 2021

Abstract The endometrium, the mucosal lining of uterus, undergoes dynamic changes throughout menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps human uterus three-dimensional endometrial organoid cultures. dissect signaling pathways that determine cell fate epithelial lineages lumenal glandular microenvironments. Our benchmark organoids reveals states regulating differentiation secretory ciliated both vivo vitro. In vitro downregulation WNT or NOTCH increases efficiency along lineages, respectively. utilize our cellular deconvolute bulk data from cancers endometriotic lesions, illuminating types dominating each these disorders. These mechanistic insights provide a platform for future development treatments common conditions including endometriosis carcinoma.

Language: Английский

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Endometrial function in women with polycystic ovary syndrome: a comprehensive review

Human Reproduction Update, Journal Year: 2020, Volume and Issue: 27(3), P. 584 - 618

Published: Oct. 21, 2020

Abstract BACKGROUND Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. An endometrial component has been suggested to contribute subfertility and poor reproductive outcomes in affected women. OBJECTIVE AND RATIONALE The aim this review was determine whether there sufficient evidence support that function altered women with PCOS, clinical features PCOS affect endometrium, are evidence-based interventions improve dysfunction SEARCH METHODS extensive literature search performed from 1970 up July 2020 using PubMed Web Science without language restriction. included all titles abstracts assessing a relationship between function, role played by biochemical/hormonal factors related potential aimed PCOS. All published papers were if considered relevant. Studies having specific topic/hypothesis regarding cancer/hyperplasia excluded analysis. OUTCOMES Experimental data suggest endometrium differs when compared healthy controls. Clinical characteristics syndrome, alone and/or combination, may dysregulation expression sex hormone receptors co-receptors, increase insulin-resistance impaired glucose transport utilization, result chronic low-grade inflammation, immune dysfunction, uterine vascularity, abnormal gene cellular abnormalities Among several date, only lifestyle modification, metformin bariatric surgery have highest scientific for benefit. WIDER IMPLICATIONS Endometrial trophoblast invasion placentation can predispose miscarriage pregnancy complications. Thus, patients their health care providers should advise about these risks. Although currently no intervention be universally recommended reverse women, modifications underlying obese insulin resistant patients. Bariatric shown its efficacy severely patients, but careful evaluation benefit/risk ratio warranted. Large scale randomized controlled trials address possibilities.

Language: Английский

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Evaluation of menstrual irregularities after COVID-19 vaccination: Results of the MECOVAC survey

Open Medicine, Journal Year: 2022, Volume and Issue: 17(1), P. 475 - 484

Published: Jan. 1, 2022

We investigated menstrual irregularities after the first and second doses of COVID-19 vaccine. Women answered a customised online questionnaire (ClinicalTrial.gov ID: NCT05083065) aimed to assess vaccine type, phase cycle during which was administered, occurrence doses, how long this effect lasted. excluded women with gynaecological non-gynaecological diseases, undergoing hormonal non-hormonal treatments, in perimenopause or menopause, as well those who had irregular cycles last 12 months before administration. According our data analysis, approximately 50-60% reproductive-age received dose reported irregularities, regardless type administered The seems be slightly higher (60-70%) dose. Menstrual both were found self-resolve half cases within two months. Based on these results, we suggest consider elements counselling receive vaccine, letting them know about potential temporary self-limiting subsequent month(s).

Language: Английский

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Deciphering the endometrial niche of human thin endometrium at single-cell resolution

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(8)

Published: Feb. 15, 2022

Thin endometrium has been widely recognized as a critical cause of infertility, recurrent pregnancy loss, and placental abnormalities; however, access to effective treatment is formidable challenge due the rudimentary understanding pathogenesis thin endometrium. Here, we profiled transcriptomes human endometrial cells at single-cell resolution characterize cell types, their communications, underlying mechanism growth in normal during proliferative phase. Stromal were most abundant type endometrium, with subpopulation proliferating stromal whose cycle signaling pathways compromised Both RNA sequencing experimental verification revealed cellular senescence stroma epithelium accompanied by collagen overdeposition around blood vessels. Moreover, decreased numbers macrophages natural killer further exacerbated thinness. In addition, our results uncovered aberrant SEMA3, EGF, PTN, TWEAK causes for insufficient proliferation Together, these data provide insight into therapeutic strategies regeneration treat

Language: Английский

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Uterine bleeding: how understanding endometrial physiology underpins menstrual health

Nature Reviews Endocrinology, Journal Year: 2022, Volume and Issue: 18(5), P. 290 - 308

Published: Feb. 8, 2022

Language: Английский

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Endometrial receptivity in women of advanced age: an underrated factor in infertility

Human Reproduction Update, Journal Year: 2023, Volume and Issue: 29(6), P. 773 - 793

Published: July 19, 2023

Abstract BACKGROUND Modern lifestyle has led to an increase in the age at conception. Advanced is one of critical risk factors for female-related infertility. It well known that maternal positively correlates with deterioration oocyte quality and chromosomal abnormalities oocytes embryos. The effect on endometrial function may be equally important factor influencing implantation rate, pregnancy overall female fertility. However, there are only a few published studies this topic, suggesting area been under-explored. Improving our knowledge aging from biological (cellular, molecular, histological) clinical perspectives would broaden understanding risks age-related OBJECTIVE AND RATIONALE objective narrative review critically evaluate existing literature focus synthesizing evidence impact conception success. This provide insights into gaps application research findings promote development treatment options field. SEARCH METHODS was prepared using PubMed (Medline) until February 2023 keywords such as ‘endometrial aging’, ‘receptivity’, ‘decidualization’, ‘hormone’, ‘senescence’, ‘cellular’, ‘molecular’, ‘methylation’, ‘biological age’, ‘epigenetic’, ‘oocyte recipient’, donation’, ‘embryo transfer’, ‘pregnancy rate’. Articles language other than English were excluded. OUTCOMES In endometrium, alterations occur cellular, histological levels negative biology impair receptivity. Additionally, advanced influences cellular senescence, which plays role during initial phase major obstacle suitable senolytic agents aging. Aging also accountable chronic conditions associated inflammaging, eventually can lead increased pro-inflammation tissue fibrosis. Furthermore, epigenetic regulation thus altering relation between its chronological age. donation cycles determine receptivity respect rates implantation, pregnancy, miscarriage, live birth have revealed contradictory inferences indicating need future mechanisms corresponding causal effects women’s WIDER IMPLICATIONS Increasing infertility IVF failures. Based complied observations synthesized conclusions review, shown functioning. information recommendations focusing molecular composition, transcriptomic changes further prospective needed explore newly emerging therapeutic options, target without affecting decidualization. Moreover, trial protocols, cycles, beneficial direct implications outcomes.

Language: Английский

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The Thyroid Hormone Axis and Female Reproduction

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 9815 - 9815

Published: June 6, 2023

Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption thyroid has been linked to reproductive dysfunction in women and is associated with menstrual irregularity, infertility, poor pregnancy outcomes, gynecological conditions such as premature ovarian insufficiency polycystic syndrome. Thus, complex molecular interplay between hormones involved functions further compounded by association certain common autoimmune states disorders HPG axes. Furthermore, prepartum intrapartum states, even relatively minor disruptions have shown adversely impact maternal fetal some differences opinion management these conditions. In this review, we provide readers a foundational understanding physiology pathophysiology hormone interactions We also share clinical insights into reproductive-aged women.

Language: Английский

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An integrated single-cell reference atlas of the human endometrium

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(9), P. 1925 - 1937

Published: Aug. 28, 2024

The complex and dynamic cellular composition of the human endometrium remains poorly understood. Previous endometrial single-cell atlases profiled few donors lacked consensus in defining cell types. We introduce Human Endometrial Cell Atlas (HECA), a high-resolution reference atlas (313,527 cells) combining published new transcriptomics datasets 63 women with without endometriosis. HECA assigns identifies previously unreported types, mapped situ using spatial validated independent single-nuclei dataset (312,246 nuclei, donors). In functionalis, we identify intricate stromal-epithelial coordination via transforming growth factor beta (TGFβ) signaling. basalis, define signaling between fibroblasts an epithelial population expressing progenitor markers. Integration large-scale endometriosis genome-wide association study data pinpoints decidualized stromal cells macrophages as most likely dysregulated is valuable resource for studying physiology disorders, guiding microphysiological vitro systems development.

Language: Английский

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Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review

Human Reproduction Update, Journal Year: 2024, Volume and Issue: 30(5), P. 584 - 613

Published: May 25, 2024

Abstract BACKGROUND The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) intrauterine adhesions (IUA), or atrophy (EA) thin endometrium (TE), can either originate autonomously arise as a result from conditions (i.e. endometritis congenital hypoplasia), medical interventions (e.g. surgeries, hormonal therapies, uterine curettage radiotherapy). Affected patients may present an altered inadequate lining that hinders embryo implantation increases the risk poor outcomes miscarriage. In humans, AS/IUA EA/TE are mainly treated with surgeries pharmacotherapy, however reported efficacy these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE This review comprehensively summarizes methodologies emerging biotechnologies (cellular, acellular, bioengineering approaches) treat human pathologies. Regenerative therapies derived tissues blood which were studied in preclinical models (in vitro vivo) clinical trials discussed. SEARCH METHODS A systematic search full-text articles available PubMed Embase was conducted identify original peer-reviewed studies published English between January 2000 September 2023. terms included: human, uterus, endometrium, syndrome, adhesions, atrophy, endometritis, hypoplasia, curettage, radiotherapy, therapy, bioengineering, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, hormone, progesterone, estrogen. Preclinical cellular, strategies repair regenerate included. Additional identified through manual searches. OUTCOMES From total 4366 records identified, 164 (3.8%) included for review. Due heterogeneity study design measured outcome parameters both studies, findings evaluated qualitatively quantitatively without meta-analysis. Groups using cell-based treatments pathologies commonly employed mesenchymal cells (MSCs) bone marrow umbilical cord. Alternatively, acellular based plasma (PRP) extracellular vesicles gaining popularity. These accompanied by emergence matrix (ECM)-derived hydrogels synthetic biosimilars sustain local delivery reporting promising results. Combined target multiple aspects regeneration remain testing but shown translational value. highlights myriad material sources, administration methods, carriers been tested. WIDER IMPLICATIONS Therapies promote proliferation, vascular development, help restore function and, ultimately, fertility. Based existing evidence, cost, accessibility, availability we propose development triple-hit strategies, potentially combining high-yield MSCs cord) (PRP), possibly integrated ECM hydrogels. Advances together insights will pave way developing personalized treatment regimens infertility-causing disorders such AS/IUA, EA/TE, endometritis. REGISTRATION NUMBER https://osf.io/th8yf/

Language: Английский

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